Index

1. Diabetes mellitus
2. Acromegaly
3. Cushing’s syndrome
4. Thyroid
5. Thyroid child
6. Hirsuitism
7. Gynaecomastia
8. Addison’s disease
9. DSD
10. Micropenis
11. Cryptochidism
12. Hyperparathyroidism
13. Hypogonadism
14. Precocious puberty
15. Delayed puberty
16. Rickets
17. Short stature
18. Adult recurrent fractures
19. Adult sigle osteoporotic fracture
20. Carcinoid syndrome
21. Radiology
22. Nuclear medicine
23. Laboratory

1
 Approach to diabetes case
Name Age sex occupation Address marital status resides with family/alone

Educational qualification

Known case of diabetes mellitus of --- years

Presenting complaints:
Foot ulcer --- duration
Swelling of feet

History of present illness:

Details of foot ulcer –
1. Onset, injury, duration, progression
2. discharge/ pus, foul smell, blackish discoloration, pain, surrounding swelling, redness, fever
3. specific treatment received
4. preceding risk factors for foot ulcer
1. recent change of footwear-footwear injury usually on dorsal surface of foot and bony
prominences
2. exposure to heat
3. others described later

Diabetes history:
1. Age at onset of diabetes
2. Presentation
1. Symptoms/ screening
2. Initial sugars/HbA1c
3. Type of diabetes – Why?
4. Diabetes symptoms
1. Current polyuria/ polydipsia/ polyphagia
2. Weight history
3. Blurred vision due to refraction changes
5. Acute emergencies
1. Hypoglycemia
2. DKA
3. HHS
4. Lactic acidosis
6. Complications – Microvascular
1. Patient awareness of complications/ need for screening
2. Neuropathy
1. +ve: more at night, disturbs sleep classically
1. Dysesthesias:
1. burning sensation of feet
2. pins/needle sensation/ tingling
3. pain
4. hot or cold sensation
5. aching

2
 2. hyperesthesia
3. paresthesia
4. radicular pain
2. –ve –
1. Numbness
2. slippage of chappals without awareness
3. feeling of cotton wool sensation
4. unsteady while walking in dark/closing eyes
5. unable to feel hot/cold sensation

3. Foot ulcers/ amputations – currently or in the past: duration for healing, admission required,
iv antibiotics, debridement, amputation, skin graft
4. Footwear history – Appropriate or not
5. Risk factors for foot ulcer – Barefoot walking
6. General foot hygiene
7. Foot care awareness/ education
8. Autonomic neuropathy
1. Postural dizziness
2. Gustatory sweating – Sweating of upper half of body while eating
3. GIT – upper – Gastroparesis – postprandial fullness, early satiety, vomiting
4. Genito – Erectile dysfunction, impotence
5. Urinary – Unable to feel bladder sensation, lump lower abdomen, poor stream, need to press
lower abomen while passing urine, double void, recurrent UTIs, urinary incontinence
6. GIT –Lower – Alternating constipation alternating with diarrhea, fecal incontinence
7. Nephropathy
1. Swelling of feet/ periorbital puffiness while getting up from sleep
2. Uremic symptoms – nausea, vomiting, poor appetite
3. Evaluation of proteinuria/ serum creatinine before
4. Retinopathy
1. Vision – Near/ distant- Glasses. Whether able to read newspaper or not?
2. Floaters
3. Any episode of sudden vision loss
4. Formal eye assessment by Eye specialist with dilated eye – Yes or no?
5. Cataracts – Yes/ No
6. Laser in past?
7. Complications – Macrovascular
1. CAD – History of typical/ atypical chest pain on exertion, dyspnea, documented MI in past
2. CVD – Past history suggestive of stroke/TIA/ acute hemiparesis
3. PAD –
1. Intermittent claudication –
1. Sites:
1. Infrainguinal (tibioperoneal) occlusive disease: involves the calf
muscles, common in the diabetic population
2. aortoiliac occlusive disease: involve buttocks or thighs
2. claudication distance
3. occur sooner with more rapid walking or walking uphill
2. ischemic pain at rest
3. nonhealing ulceration of the foot

3
 4. frank ischemia of the foot
8. Other complications – Infections – vulvovaginitis/ balanoposthitis, TB, depression, eating
disorders, dental problems
9. CVD risk factors
a. HTN, dyslipidemia, smoking
10. Obesity – and effects of obesity

11. Initial treatment

1. Diet
2. Lifestyle
3. OHAs – Name, type, duration, when changed – why
4. Insulin - Indication
12. Insulin
1. Dose – Units/Kg
2. Type – Regular/NPH or analogs
3. Regimen – Premixed/ Mix split
4. Injected by self/ others
5. Site of injection – Abdomen/ thighs/ arms
6. Timing in relation to meals
7. regular or not
8. Where bought from – standard medical shop/ cold chain maintenance
9. Does patient check expiry date before purchase
10. Storage at home – Refrigerator
11. Injection technique – Pen or syringe – 40 IU/100IU/ml, loading and injecting
12. Any formal training or education
13. Syringe – 1 syringe how many days? How and where disposal?
14. Does patient adjust insulin doses as per blood sugars?
13. Glucose monitoring
1. Frequency of check
2. Mode – Lab/ home glucometer
3. Aware of HbA1c or not
4. Glycemic control – Poor or good based on HbA1c or FPG/PPPG
5. Targets awareness
6. Hypoglycemia
1. Frequency/ timing
2. Mild/severe
3. Symptoms – Autonomic/ neuroglycopenic
4. Any admissions needed for hypoglycemia
5. Awareness
6. Knowledge of correction/ prevention
14. Diet
1. Timing, regularity, similar quantities or not
2. Veg/ non-veg, meal pattern
3. Calories/ carb/ protein/ fat appropriate or not
4. Oils
5. Awareness of good or bad foods for diabetics
6. Formal review by dietitian – Yes/ No
7. Meals cooked by

4
15. Exercise
1. Type: Aerobic/ weight bearing
2. Duration
3. Regular or not
4. If on insulin, precautions for exercise
a.
16. Treatment history - Where following up? Drug details? Allergies?
17. Past history:
a. Past H/O TB/ATT
b. Hypothyroidism
18. Personal history – Smoking/ alcohol
1. Menstrual history
19. Family history – Diabetes/ HTN/ premature CVD/ dyslipidemia in parents and siblings

History summary:
1. …… year old male patient with diabetes mellitus (type 2) of …… years duration
2. with poor glycemic control on OHAs
3. presents with non-healing foot ulcer …. foot after injury
4. on background of diabetic neuropathy and poor foot care
5. The ulcer is large needing multiple surgeries including amputation of ….. and likely infected.
6. No history to suggest PVD or CAD or CVD.
7. He has microvascular complications in the form of DSPN and needs formal evaluation for
nephropathy and retinopathy.
8. ±weight loss
9. ±DKA
10. ±OHA response/ failure

EXAMINATION

Patient comfortable

Anthropometry :
Weight Kg Height cm,

BMI Kg/m2
Waist circumference -- WHR –

Vitals:
1. Pulse - /min, regular, normal volume, normal character, all peripheral pulses palpable, vessel
wall, carotid bruit
2. BP - mmHg, postural fall in BP
3. RR
4. Temp

Cardinal signs: Pa/ I/ Cy/ Cl / PE/ L’pathy

Skin – Acanthosis nigricans, insulin injection sites, capillary refilling time

5
Mucous membranes –
Teeth and gums for periodontitis
Joints:
Thyroid
Testes –

Feet –
1. Gross inspection –
1. Deformities
2. clawing of toes
3. prominent metatarsal heads
4. gangrene, line of demarcation between normal and ischemic region
5. ulcer
6. old amputation
7. foot arches

2. Dermat examn –
1. Hair loss
2. dry skin
3. pigmentation
4. cracks over sole/heel
5. nails dystrophic, brittle
6. webspace maceration
7. old scars
8. callus
9. corn
10. hallux valgus (bunion)
11. bullae

3. Neuropathy examination –
1. Semess-Weinstein 5.07, 10 g/cm2 – Monofilament
2. Vibration
3. Proprioception
4. Pinprick
5. Fine touch
6. Temperature
7. Ankle jerks

4. Vascular examination –
1. Dorsalis pedis, post tibial, popliteal, femoral artery: weak, bounding
2. bruit: iliac or femoral arteries
3. capillary refilling time

5. Biomechanical foot assessment –

1. Plantar and dorsi flexion of ankle
2. Gait
3. foot wear
4. whether patient can inspect feet

6
Foot ulcer
1. Inspection
1. Site
2. Size
3. Number
4. Margin: transitional zone of skin around ulcer
5. Edge:
1. Slopping
2. Undermined
3. Punched out
4. Rolled
5. everted
6. Floor-the exposed part of an ulcer
1. granulation tissue
2. Discharge: scab (dry),
3. Slough: unseprated necrotic tissue
4.
7. Edge-the part between the margin and the floor of an ulcer

2. Palpation
1. Depth
2. tenderness
3. Base-the structure on which the ulcer rests
4. Probe test for osteomyelitis
5. Temperature
3. Surrounding skin
1. redness
2. swelling
3. warmth
4. hyperpigmentation
4. lymph nodes
Healing –
1. Margin: 3 lines: White (outer) -blue-red (inner)
2. Slopping soft edge
3. red granulation tissue
4. no slough
5. minimal serous discharge
Spreading ulcer-
1. Margin:red inflammmed irregular margin
2. Slough
3. Discharge

Chronic inflammatory
1. Margin: Thick white fibrotic
2. Pale non bleeding granulation tissue
3. Firm edge

7
CVS –
RS-
P/A-
1. Succusion splash: stethoscope over the upper abdomen and rocking the patient back and forth
at the hips. Retained gastric material greater than three hours after a meal will generate a
splash sound and indicate the presence of a hollow viscus filled with both fluid and gas
1. DD- DM, post surgery, malignancy-GOO, idiopathic
2. palpable bladder
3. reduced anal tone
CNS –
1. Higher function
2. Cranial nerves
1. Visual acuity –
2. Fundus – Diabetic retinopathy
3. pupils
3. Motor
4. Sensory
5. Reflexes: bulbocavernosus reflexes
6. Cerebellar signs
7. Palpable nerves: greater auricular, posterior tibial, ulnar

Clinical pointers to autonomic neuropathy – resting tachycardia, postural fall in BP, succusion splash,
pupils, palpable bladder, bulbocavernosus reflexes, reduced anal tone

Final diagnosis:

1. Diabetes mellitus – Type 2

2. Underweight / Normal Weight / overweight/ obese
3. Poor glycemic control
4. Diabetic foot ulcer
1. Site
2. Grade – Wagner, University of Texas, PEDIS
5. Distal symmetric peripheral neuropathy
6. Diabetic retinopathy – Mild NPDR
7. Diabetic nephropathy – Proteinuria
8. Autonomic dysfunction
9. No macrovascular complications
10. HTN
11. Dyslipidemia

8
 Management

1) Investigation
a. Assessment of glycemic control- Sugars, HbA1c
b. Complication and CVD risk screen
i. Fundus
ii. Urine alb
iii. Serum creatinine
iv. Lipids fasting
v. LFT
vi. ECG
c. Inv for foot ulcer
i. X-ray lytic lesion, arches, soft tissue swelling, vascular calcification
ii. Hb, TLC, DLC
iii. Deep tissue C/S
iv. Blood C/S
v. ABI(40+20+30+40)

vi. Arterial Doppler of lower limbs

2) Treatment
a. Foot ulcer
i. Debridement, i.v. abx, off-loading
b. Glycemic control
i. Diet, insulin
c. CVD risk factor

9
 Questions Epidemiology

1. Genetics in T2DM
1. Twin concordance (91%)- Diabetalogia 1981
2. US caucasions 2-4% T2DM
3. Afro-americans 4 to 6% T2DM
4. Pima Indians approximately 40% T2DM
5. Micronesians from Naura approx 30% T2 DM

2. T1DM twin concordance 25%

3. Prevalence in India T2DM –

1. Rural – 4%

2. Urban – 10 to 18%

4. Affluent Lucknow prevelance (Asiana study Indian J Med Res 2008)

1. Hypertension 30%

2. pre-hypertension 30%

3. elevated LDL cholesterol (25%)

4. Pre diabetes (40%)

5. smoking (20% males)

6. T2DM: 20% (Diabetes Res Clin Pract 2008)

5. Inheritance

1. Type 2

1. Single parent – 50%

2. Both parents – 90%

2. Type 1

1. 8 % - father, 4 % mother

2. Both

10
11
Questions - Pathogenesis

1. What is monogenic diabetes?

1. 1% to 2% of all cases

2. Loosely divided into

1. neonatal diabetes (diabetes appearing within the first 6 months of life)

1. Mutations involving the KATP channel account for most cases,

responds to sulfonylureas, which block the persistently open, mutated
KATP channels, thus allowing insulin secretion

2. MODY; diagnosed outside the neonatal period and generally prior to 25 years
of age

1. MODY is associated with mutations involving glucokinase or genes

coding transcription factors that are important in insulin signaling

2. Who should be screened for diabetes?

1. screen the general population at 3-year intervals starting at age 45 years

2. Earlier or more frequent screening should be performed in adults with a body mass
index (BMI) 25 kg/m2 or greater and additional risk factors

3. TABLE
Additional Risk factors prompting screening for Type2 DM in adults
1. Physical inactivity
2. Diabetes in a first-degree relative
3. High-risk ethnicity: African American, Native American, Latino, Pacific
Islander, Asian
4. History of gestational diabetes or of delivering a baby weighing > 4 kg
5. Hypertension: BP > 140/90 mm Hg or current hypertension therapy
6. HDL cholesterol < 35 mg/dL or TG > 250 mg/dL
7. PCOS
8. Pre diabetes
9. Clinical evidence of insulin resistance: acanthosis nigricans, pronounced
obesity

3. What are the genetics of type 1 diabetes?

1. The exact role of genetics is unknown

4. HLA DR in north Indians for IDDM (Diabetes 1985)

1. HLA-DR3: RR of 10 much higher than that reported in the Western IDDM
population

12
 2. HLA-DR2 showed a significant negative association; RR = 0.2
3. DR4 had no relationship with IDDM

5. What are the genetics of type 2 diabetes?

1. Polygenic

6. LADA definition

1. Type 2 diabetic phenotype

2. islet antibodies

3. prevalence of LADA: 10% among subjects of diabetes aged 40–75 years (Diabetes
2005)

4. Strict criteria (Diabetologia 2005):

1. age >30 years at diagnosis

2. insulin independence for at least 6 months after diagnosis

3. antibodies present

7. NAFLD

1. Normal – 20- 30%

2. DM – 50 -70%

3. Indian data – 10-30%

8. Dawn phenomen –

1. Counter regulatory hormones elevated – GH, cortisol, decreased insulin

9. Somoyogi

1. Excess insulin

10. Lipohyperthropy mechanism

1. Repeated injections at same site

2. local trophic action of insulin

13
11. NODAT

1. Early: < 1 yr

2. Late: > 1 yr

3. Causes – cyclosporine, tacrolimus, prednisolone

4. basiliximab RR 2.3 (SGPGIMS nephrology dept……Nephrology

(Carlton) 2014)

Am J Transplant 2014

12. What techniques are available to assess insulin resistance?

1. Gold standards for defining insulin resistance are the research tools
1. intravenous glucose tolerance test
2. insulin suppression test
3. euglycemic insulin clamp

2. Clinically applicable -:
HOMA-IR = Fasting Insulin (mU/L) x Fasting Glucose (mmol/L)/22.5

13. Describe metabolic syndrome

Defined as the presence of three of the five following criteria:
1. Increased waist circumference (> 40 inches in men, > 35 inches in women)
2. Plasma triglycerides > 150 mg/dL
3. Plasma high-density lipoprotein cholesterol > 40 mg/dL in men, > 50 mg/dL in
women
4. Blood pressure > 130 mm Hg systolic/85 mm Hg diastolic

14
 5. Fasting plasma glucose > 100 mg/dL
In 2004, AHA modified this definition to include the use of medications for hypertension and
hyperglycemia to the fasting plasma glucose levels

14. What causes beta-cell failure in type 2 diabetes?

Many potential triggers
1. Glucolipotoxicity: Elevations of glucose and free fatty acids
2. chronic increases in certain cytokines, notably tumor necrosis factor-alpha (TNF-a)
and interleukin-1 beta (IL-1b)
3. activate ―death‖ genes (caspases) in beta cells

15. Edema in diabetes –

1. Insulin

2. Amlodepine

3. Pioglitazone

16. Anemia in diabetes –

1. CKD

2. Metformin

3. Pioglitazone

17. DM in Endocrinopathies
1. Acromegaly: 40%
2. GH theraphy increase DM sixfold

18. Risk factors for DM

1. Prevalence of DM in overweight vs. normal(3 times higher)

19. Can diabetes be prevented?

1. Potential beneficial effects in Type 2 DM
1. thiazolidinediones
1. Troglitazone in Prevention of Diabetes [TRIPOD]
2. Diabetes Reduction Assessment with Ramipril and Rosiglitazone
Medication [DREAM]
2. metformin (Diabetes Prevention Program [DPP])
3. alpha-glucosidase inhibitors (Study to Prevent Non–Insulin-Dependent
Diabetes Mellitus [STOP-NIDDM] study
4. intestinal lipase inhibitors (XENical [orlistat] in the Prevention of Diabetes in
Obese Subjects [XENDOS] study)

15
 5. insulin (Outcome Reduction with Initial Glargine Intervention [ORIGIN] trial
6. Lifestyle modification (7% weight loss and moderate exercise for 150
minutes/week) arm of the DPP showed excellent results, with a 60% lower
risk for development of diabetes than those receiving metformin (30%)
American Diabetes Association (ADA) recommends pharmacotherapy only in patients who are at
high risk for progression to diabetes because of multiple risk factors or an HbA1C level higher than
6% despite lifestyle modifications.

Identifying people in the prediabetic phase of type 1 diabetes requires serial measurements of beta-
cell function and close monitoring of immunologic markers, making selection of an appropriate
cohort difficult.
Prevention of progression to type 1 diabetes.
1. Diabetes Prevention Trial–Type 1 (DPT-1) - insulin
2. European Nicotinamide Diabetes Intervention Trial (ENDIT) - nicotinamide

16
Questions Pancreatic disease and diabetes

1. Acute pancreatitis
1. Transient hyperglycemia: elevated glucagon
2. rarely permanent DM:
1. beta cell damage
2. Fulminant disease with multiorganfailure – 25%
3. DKA: 10% may have acute pancreatitis

2. Chronic pancreatitis and DM

1. 60% at 20 years
2. Difficult to control
3. Severe prolonged hypoglycemia: loss of alpha cells
4. Dilated ducts with plugs
5. Small Calculi
6. Calcific pancreatitis app. 60% vs non-calcific app. 30%
7. Lower frequency of macrovascular complications: less dyspidemia
8. Insulin required: 80%
3. Exocrine function tests
1. Urine ecxcretion products of orally ingested
1. PABA (historical interest):
1. Bentiromide was administered by mouth
2. metabolized by pancreatic chymotrypsin
3. liberated PABA
2. Flouroscein dilauranate
2. Fecal:
1. chymotrysin
2. elastase: advanced disease (< 100 μg/g of stool)
3. pancreatic output measurement after Lund test meal
4. Dual-label Schilling test
1. Malabsorption of vitamin B12 has been observed in 30–50% of patients
2. based on the relative absorption of R-protein–cobalamin and intrinsic factor–
cobalamin
3. R-proteins are non-intrinsic factor cobalamin-binding proteins present in
saliva and gastric juice
4. pancreatic proteases degrade R-proteins and allow intrinsic factor to bind to
vitamin B12
5. the following are given orally to the test subject:
1. [57Co]cobalamin–intrinsic factor
2. [58Co]cobalamin–R-protein
3. cobinamide, a cobalamin analogue that binds only to R-protein and
serves to saturate endogenous R-protein and prevent it from
competing for [57Co]cobalamin–intrinsic factor
4. excess intrinsic factor to bind to [58Co]cobalamin after the removal of
R-protein
6. Following ingestion, urine is collected for 24 hr
7. ratio is calculated of [58Co] to[57Co]

17
 8. pancreatic insufficiency: ratio is low as [58Co]cobalamin attached to R-
protein is not liberated and cannot be bound to intrinsic factor for absorption

5. Faecal fat analysis

1. Maldigestion of fat only occurs after ≥ 90% of pancreatic lipase secretory
capacity is lost
2. 72-h collection of stool whilst the patient is on a diet of 100 g/day of fat
3. Faecal fat quantities of ≥ 7 g/day are considered to be abnormal
6. Secretin stimulation test
1. 0.2 μg/kg body weight
2. endoscopy is performed in the standard fashion
3. duodenal fluid are collected at 15 min, 30 min, 45 min and 60 min after
injection of secretin
4. peak bicarbonate < 80 mEq/L is considered abnormal
5. very high sensitivity but low specificity
6. most useful for ruling out disease
4. Hereditary chronic pancreatitis
1. PRSS1: cationic trypsinogen
2. anionic trypsinogen (PRSS2) G191R protects against chronic pancreatitis
3. SPINK1: serine protea inhibitor, Kazal type 1
4. CFTR
5. chymotrypsinogen C (CTRC)
5. FCPD
1. Large calculi, marked duct dilatation, severe fibrosis, fast evolution, DM > 90%
2. Low to middle income countries
3. SPINK1 N34S variant
4. CTRC
5. 100 fold higher risk of pancreatic carcinoma

6. DM in Ca pancreas

1. Cause: islet destruction, decreased insulin secretion

2. Frequency: Prev of DM 20 to 50%

3. Recent diabetes: 40% of pts with Ca pancreas and DM

4. Poorer prognosis
5. Most treated with OHA
6.

7. Ca pancress in DM

1. Cause: T2DM, chronic pancreatitis, FCPD

2. Frequency:

3. Back pain, jaundice, weight loss inspite of good glycemic control

8. Iron deposition

1. Hemochromatosis

18
 2. Hemosiderosis

9. Hemochromatosis

1. Secondary DM

2. Cirrhosis, hepatoma

3. Bronzed skin

4. Hypopitutarism: hypogonadism, hypothyroidism

5. Joints: chondrocalcinosis, Pseudogout

6. Cardiomyopathy

10. Cystic fibrosis

11. Pancreatic surgery

1. Distal pancreatectomy app. 60% vs. whipple’s surgery app. 30%

Questions General complication

1. T2 DM at diagnosis complications:

1. HTN(70%)

2. Dyslipidemia(60%)

3. Retinopathy(40% UKPDS)

4. Nephropathy(10%)

5. Neuropathy (13%-UKPDS)

6. Neuropathy (30%-SGPGIMS) [J Postgrad Med 2014]

2. What are the acute complications of diabetes?

1. Hyperglycemia
2. hypoglycemia

3. What is DKA?
1. DKA is a state of uncontrolled catabolism
2. triggered by a relative or absolute deficiency in circulating insulin
3. accompanied by a reciprocal elevation in counterregulatory hormones (glucagon)
4. causes catabolism of fat (lipolysis)
5. provides the substrate (free fatty acids) for the uncontrolled production of ketones by
the liver
6. Production of ketones then leads to metabolic acidosis.

19
4. Is the ketone test result always positive with DKA?
1. ―delay‖ in positivity for measured ketones is due to a limitation of the laboratory test
for ketones, which detects only acetoacetate
2. predominant ketone in untreated DKA is beta-hydroxybutyrate
3. DKA is treated; acetoacetate becomes the predominant ketone, causing the test for
ketones to turn positive.

5. What lab tests are recommended in the first hour of treatment for DKA?
1. Baseline electrolytes, blood urea nitrogen (BUN), creatinine, and glucose
measurements, anion gap calculation, urinalysis, urine and blood ketone
measurements, and electrocardiogram (ECG) should be performed.
2. Arterial blood gas (ABG) analysis should be obtained
3. Fluid intake, urine output, and progression of laboratory changes should be recorded.
4. Further lab testing should be based on findings of suspected triggers (i.e., infection,
myocardial infarction).

6. Summarize the strategy for fluid and potassium administration in the first hour.
1. Fluids: Normal saline given at 15 mL/kg/h (approximately 1 L/h for a 70-kg
individual).
2. Potassium:
1. If T waves on the ECG are peaked or normal, no potassium replacement is
initially necessary
2. If T waves are low or U waves are seen, 40 mEq potassium chloride (KCl)
should be added to each liter of intravenous (IV) fluids.

7. How should insulin treatment be started with DKA?

1. IV bolus of 10 to 20 units of regular insulin should be followed by a continuous
infusion of 0.5 units/mL of regular insulin mixed in normal saline at a rate of 5 to 10
units per hour (0.1 unit/kg/h).

8. How should insulin be adjusted during treatment?

1. If the serum glucose drops to less than 250 mg/dL, fluids should be changed to a 5%
to 10% dextrose– containing solution.
2. The insulin infusion rate may be doubled if the serum glucose does not decline after
the first hour.
3. The optimal rate of glucose decline is 100 mg/dL/h.
4. The glucose level should not be allowed to fall to less than 250 mg/dL during the first
4 to 5 hours of treatment.

9. When can the insulin infusion be discontinued?

1. anion gap corrects to normal, the pH is 7.3 or greater
2. serum bicarbonate is 18 mEq/L or greater
patient can be given a subcutaneous dose of regular insulin or a short-acting insulin analog (lispro,
aspart, glulisine) to cover a meal
infusion should be stopped 30 minutes after the subcutaneous insulin is given.

10. What other interventions may be necessary in the treatment of DKA?

20
 1. If the initial serum phosphorus is less than 1.0 mg/dL, consider giving 10 to 20 mEq/h
potassium phosphate in the IV fluids.
2. Bicarbonate (in the form of sodium bicarbonate) replacement is not recommended
unless
1. other causes of severe acidosis are present (e.g., sepsis, lactic acidosis)
2. arterial pH is less than 6.9
If used, sodium bicarbonate should be diluted in the IV fluids and given over 1 hour.

11. What are the signs of HHS?

1. Marked hyperglycemia (BG > 600 mg/dL)
2. Hyperosmolarity (serum Osm > 320 mOsm/L)
3. Arterial pH greater than 7.3
4. Hyperglycemia, once triggered, leads to glycosuria, osmotic diuresis,
hyperosmolarity, cellular dehydration, hypovolemia, shock, coma, and, if untreated,
death.

12. Why is ketoacidosis typically not seen in HHS?

The presence of circulating insulin or lower levels of counterregulatory hormones (or both)
prevents lipolysis and significant ketone production. Lactic acidosis may be seen, however.

13. What role does insulin play in the treatment of HHS?

Continuous IV insulin infusion is helpful to reduce glucose levels at a predictable rate. Patients
may be transitioned directly from IV to subcutaneous insulin as described for DKA.

14. Describe the signs and symptoms of hypoglycemia.

1. Whipple’s triad
1. low blood glucose
2. symptoms consistent with hypoglycemia
3. resolution of symptoms by raising blood glucose

15. Etiology and outcome of childhood and adolescent diabetes mellitus in North India…..J
Pediatr Endocrinol Metab. 2004
1. Type 1 DM comprised 81%, type 2 DM 8%, and fibrocalculous pancreatic DM 9% of patients
2. Retinopathy was present in 22% and nephropathy in 18% of those with DM duration ≥ 5 years
3. frequency of DKA and severe hypoglycemia was 5.0 and 3.3 episodes per 100 patient years
4. Mortality was 7% over 823 person years of follow up.

16. How does chronic hyperglycemia affect cellular function?

1. Nonenzymatic mass-action glycation of proteins: These proteins ultimately form
advanced glycosylation end products (AGEs), which are associated with altered
protein function. AGEs have been found in the connective tissue of blood vessels and
in the renal glomerular matrix and have been shown to modify low-density
lipoprotein (LDL) composition.
2. Enzymatic conversion of glucose to sorbitol by aldose reductase in the eyes and
peripheral nerves: Because the cellular clearance of sorbitol is extremely slow, it

21
 accumulates as an osmotically active molecule. This accumulation is also associated
with neuronal myoinositol depletion.
3. Excess intracellular glucosamine: Another product of glucose, intracellular
glucosamine has been linked to endothelial dysfunction and to impaired insulin
action.
4. Activation of protein kinase C (PKC) by glucose: Thought to be due to depressed
nitric oxide production and increased endothelin-1 activity, activation of PKC has
been shown to mediate retinal and renal blood flow abnormalities and to increase
endothelial cell permeability.
5. Hyperglycemia-driven oxidative stress: The resulting activation of poly(ADP-ribose)
polymerase (PARP) has been tied to glycemic injury and may serve, in part, to
increase substrate flux into AGE, polyol, and glucosamine formation and to promote
PKC activation.

22
Retinopathy
1. Visual loss

1. Painful –

1. Chronic simple glaucoma

2. Painless –

1. Gradual – cataract, retinopathy

2. Acute –

1. CRAO--- mild increase in DM(frequent in DM)

2. CRVO--- mild increase in DM (frequent in DM)

3. vitreous h’age

2. Floaters:

1. Mechanism

1. condensation in the vitreous jelly

2. new blood vessel may leak blood into the vitreous

2. DD-

1. Myopia

2. Age related

3. Retinal detacment

3. Significant-

1. Sudden

2. Multiple

3. Non-retinal
1. Extraorbital and lid – Styes, xanthelasma, DKA –Mucormycosis
2. Extraocular muscles –
1. 3rd n. palsy – mononeuritis multiplex, painful, pupil sparing in 80%, self-
improving, neuro r/v if pupil affected, pupil fibers in peripheray of optic
nerve
2. 6th nerve
3. Cornea – Reduced sensation, corneal ulcer with contact lens
4. Iris – Rubeosis iridis, neovascular glaucoma
5. Open angle glaucoma

23
 6. Lens – Refractive changes due to change in blood sugars – don’t prescribe glasses,
premature or advancing cataract, diabetic cataract

4. How common is diabetic retinopathy and how is it managed?

1. If glucose levels are not controlled, up to 70% of type 1 diabetics may experience
proliferative retinopathy over their lifetime.
2. Among type 2 diabetics, 21% may have significant nonproliferative and even
proliferative retinopathy or macular edema at the time of diagnosis.

5. Other drugs for retinopathy

1. Fenofibrate

6. What are the risk factors for development of diabetic retinopathy?

1. Duration of diabetes
2. Level of glycemic control
3. Presence of hypertension
4. Diabetic nephropathy is strongly associated with proliferative retinopathy in type 1
diabetes and insulin-treated type 2 diabetes.
7. Side PRP
1. Reduced peripheral vision
2. Reduced night vision

8. Eye complications in diabetic: DD

1. DM
2. HTN
3. AIDS
4. Carotid atherosclerosis
9. Retinopathy – periphery> central usually

1. International Classification
Retinopathy level Features Mgt
No DR - Annual eye screen
NPDR – Mild Microaneurysms only Annual eye screen if macula
not involved
NPDR – Moderate > Mild and < Severe Fundus – 3-6 monthly
Dot, blot h’ages, hard exudates Good glycemic, BP and lipid
control
Stop smoking
NPDR – Severe IRMAs > 1 quadrant 2-3 monthly
Venous caliber changes – beading in > 2 Consider panretinal
quadrant photocoagulation
>20 H’ages in 4 quadrants
PDR NVD Panretinal photocoagulation if
NVE high risk
anti- VEGF- Bevacizumab, 2
monthly f/u
Advanced PDR Traction RD, Vitreous H’age Vitrectomy for fibrosis

24
 Maculopathy – Any thickening of retina , 2 disc Focal laser photocoagulation
CSME diameters from center of macula intra macular triamcinolone ?
Any hard exudates , 2 disc diameters
from center of macula with associated
thickening of the retina

TABLE

Nephropathy

1. Occurrence of nephropathy in DM pts

1. T1DM= upto 40%
2. T2DM = upto 25%

2. CKD MBD:

1. Causes

1. Po4 retention

2. Low calcitrol

3. Low calcium

4. Skeletal resistance

2. Types

1. Biochem

2. Soft tissue

3. Bone

1. High turnover

2. Low turnover –

1. adynamic bone disease – DM, hypoparathyoidism

2. osteomalacia

3. Mixed turnover

3. Renal hypoglycemia

1. Increased insulin half life, decresed clearence

2. Decresed glycogen

25
 3. Decreased gluconeogenesis

4. AN – decresed absorption, hypoglycemic unawareness, loss of appetite

4. Slow the rate of progression of renal failure in patients with nephropathy.

1. Improved blood pressure and glucose control
2. either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor
blocker (ARB)
3. reduction of dietary protein intake ??? KDQKI for, ADA against

ABLE 2-4. STAGING OF CHRONIC KIDNEY DISEASE

5. What factors affect the development of diabetic nephropathy?
Known risk factors for diabetic nephropathy are as follows:
1. Family history of hypertension (RR 4)
2. Sibling with diabetic nephropathy (RR 4)
3. Black race (RR 3 vs. white race)
4. Smoking history (RR 2)
5. History of poor glycemic control (RR 2)
6. Genes coding for essential hypertension

6. Markers

1. WT1 protein in urinary exosomes (SGPGIMS molecular med dept…..PLoS

One 2013)

7. genes in nephropathy

1. VEGFA

2. IL-1

3. MMP9

4. EPO

5. IL-8

6. ADIPOQ

7. IL-10

8. role of combination of ACEI and ARB… ADA 2014 and KDOQI 2012

1. Either ACE inhibitors or ARBs (but not both in combination) are

recommended for elevated urinary albumin excretion

2. ONTARGET: NEJM 2008. increased risk

26
1. hypotensive symptoms

2. syncope

3. renal dysfunction

27
Neuropathy

1. Prev of neuropathy in T2 DM

1. Clinic based study 25% to 30%

2. Population based study- 30 – 50%
3. Neuropathy in new onset DM – 30%(SGPGIMS) [J Postgrad Med 2014 ]

2. Neuropathy in DM due to non diabetic causes

1. 20 -30%

2. 5% Rochester diabetic neuropathic study (neurology 1993)

3. matched control: 10%(SGPGIMS) [J Postgrad Med 2014 ]

3. Semmes - Weinstein monofilament

1. 5.07/10 g

2. dorsal 1st webspace; plantar surface digit 1, 3, 5; meta-tarsal heads 1, 3, 5; medial and
lateral mid-foot; heel

3. did not perceive the filament at 3 or more of the 10 sites: abnormal

4. Bioasthesiometer:

1. vibrates at an amplitude proportional to the square of the applied voltage

2. applied perpendicular to the test site with a constant and firm pressure
3. distal plantar surface of great toe of both the legs
4. If great toe was affected by ulcer, VPT was measured at the base of the first, third or fifth
metatarsals
5. voltage was slowly increased at the rate of 1 mV/sec
6. VPT value was defined at voltage level when the subject indicates first felt vibration sense
7. DN diagnosed if the VPT was ≥ 25mV

8. Name the types of diabetic neuropathies.

There are four principal types:
1. distal symmetric polyneuropathy
2. diabetic amyotrophy
3. diabetic mononeuropathy
4. autonomic neuropathy

5. Summarize the symptoms of distal symmetric polyneuropathy.

1. usually discovered on physical examination
2. loss of vibratory sense in the toes and loss of ankle reflexes
3. Light touch and pinprick sensations are subsequently lost

28
4. Common associated symptoms are paresthesias and numbness of the feet, especially at night
5. paresthesias may evolve to severe knifelike or burning pain, which can be disabling.

6. Explain the basic pathophysiology of distal symmetric polyneuropathy.

1. axonal degeneration
2. entrapment neuropathy

3. How is painful diabetic neuropathy treated?

FDA approved
1. pregabalin (starting dose 50 mg three times daily [TID] with titration to 100 mg TID,
if tolerated)
2. SNRI duloxetine (60 mg daily)
Others
3. gabapentin (starting dose 300 mg twice daily with titration to 600 mg TID, as
necessary)
4. Venlafaxine
5. Amitriptyline
6. Gabapentin
7. Valproate
8. opioids (morphine sulfate, tramadol, and oxycodone controlled-release)
9. Capsaicin: Initially, the release of substance P causes pain, but eventually the nerve
terminals become depleted of substance P, leading to loss of the pain sensation

4. What causes the foot problems in patients with diabetes?

1. Loss of proprioceptive nerve fibers can result in an abnormal gait
2. leading to ―pressure spots‖ on the foot that are signaled by the presence of thick
calluses
3. calluses may ulcerate and become infected.
4. Risk factors -Neuropathy, vascular disease, and predisposition to infection

Diabetic autonomic neuropathy

1. Autonomic neuropathy manifestations

1. CAD --- Unexplained resting tachycardia and postural hypotension

2. GIT – gastoparesis, alternate diarrhea and constipation, nocturnal diarrhea,

incontinence

3. Urinary – sensory,

4. Genital --- ED, Retrograde ejaculation, vaginal dryness

5. Salivary – gustarory sweating

2. Autonomic neuropathy exam

1. postural hypertension

29
 2. resting tachycardia

3. anal tone

4. sucussion splash

5. bulbo cavernous reflexes

6. bladder percussion

3. Gastroparesis

1. Causes

1. Amyloidosis

2. Diabetes –

1. AN

2. loss of cells of cajal

3. loss of NO

4. loss of smooth muscle cells

2. Common in

1. Type 1 – insulin is required for preservation of cells of cajal

3. Nuclear scan Test –

1. RBS < 275

2. Stop drugs 48 hrs

3. Tc 99 Sulphur colloid 300 micro Cu – roti

4. T ½ -- 83 min +/- 17 min

4. Postural hypotension
1. Management
1. Droxidopa (FDA 2014):
1. Initially 100mg three times daily, max 600 mg daily
2. directly metabolized to norepinephrine by dopa-decarboxylase

5. How common is diabetic autonomic neuropathy?

1. Sophisticated tests: up to 90% of people with diabetes have some degree of
autonomic dysfunction
2. Symptomatic: less than 50% of affected people

30
6. How does it affect survival rates?
Clinically significant autonomic neuropathy: 10-year survival rate less than 50%.

7. How is cardiac diabetic autonomic neuropathy diagnosed?

1. Lack of R-R variation during
1. deep breathing
2. Valsalva maneuver
2. Postural hypotension

CAD

1. What are the risks associated with macrovascular disease in diabetes?

1. twofold to fourfold higher risk for both CVD and PAD than the nondiabetic
population
2. 75% with diabetes will die from CVD

2. How can macrovascular disease be prevented in the diabetic population?

1. Aggressive blood pressure control, with a target blood pressure less than 140
(systolic)/80 (diastolic) mm Hg….ADA 2014
2. recommended goal for LDL cholesterol is less than 100 mg/dL (< 70 mg/dL in high-
risk patients)
3. Smoking cessation
4. exercise
5. Weight loss (if the patient is overweight).

31
 6. Low-dose aspirin therapy in high-risk individuals, but there is considerable
controversy

3. Does aggressive lipid-lowering therapy improve cardiac outcomes in diabetic patients?

HMG-CoA reductase inhibitors in reduce cardiovascular burden by 50%.

4. Does improved glycemic control in hospitalized patients affect outcome?

1. multicenter trial, Normoglycemia in Intensive Care Evaluation—Survival Using
Glucose Algorithm Regulation (NICE-SUGAR)
2. compared tight glucose control (BG target 81-108 mg/dL) with usual therapy (BG
target , 180 mg/dL)
3. primary end point being mortality at 90 days from study entry
4. Mortality was unexpectedly increased by 14% in the intensively managed group
5. no difference in secondary end points, including length of stay, rate of organ failure,
and mechanical ventilation
6. consensus is to view blood glucose no greater than 180 mg/dL as the threshold for
starting intravenous insulin in the ICU setting
7. blood glucose target between 140 and 180 mg/dL

1. data are less robust in patients hospitalized in non–critical care settings

2. meta-analysis has suggested that improved glycemic control
3. reduces the risk of infection
4. Consensus statements have established treatment targets for non–critical care
patients: preprandial BG less than 140 mg/dL and random BG level less than 180
mg/dL

5. How important is glycemic control in preventing the chronic complications of diabetes

mellitus?
1. Diabetes Control and Complications Trial (DCCT) : type 1 diabetes
2. United Kingdom Prospective Diabetes Study (UKPDS) : newly diagnosed type 2
diabetes
1. improving glycemic control reduces risk of development of microvascular
complications
2. Cardiovascular outcomes were reduced in the long-term follow-up

Recent trials involving people with long-standing type 2 diabetes:

1. ACCORD [Action to Control Cardiovascular Risk in Type 2 Diabetes]
2. ADVANCE [Action in Diabetes and Vascular Disease: Preterax and Diamicron MR
Controlled Evaluation]
3. VADT [VA Diabetes Trial])
1. significant reduction in microvascular complications
2. limited role for tight glucose control in preventing the cardiovascular
complications
3. DCCT and the UKPDS were conducted prior to statins as well as ACE
inhibitors and ARBs and the current standards of percutaneous coronary
interventions

6. Antiplatelet Agents Recommendations ….ADA 2014

32
1. aspirin therapy (75–162 mg/day) as a primary strategy in type 1 or type 2 diabetes at
increased cardiovascular risk (10-year risk >10%), this includes most men aged > 50
years or women aged > 60 years who have at least one additional major risk factor
1. family history of CVD
2. hypertension
3. smoking
4. dyslipidemia
5. albuminuria
2. Aspirin should not be recommended for CVD prevention for adults with diabetes at
low CVD risk (10-year CVD risk < 5%, such as in men aged < 50 years and women
aged ,60 years with no major additional CVD risk factors)
3. In patients in these age-groups with multiple other risk factors (e.g. 10-year risk 5–
10%), clinical judgment is required
4. aspirin therapy (75–162 mg/day): secondary prevention strategy in those with
diabetes with a history of CVD
5. patients with CVD and documented aspirin allergy, clopidogrel (75 mg/day) should
be used
6. Dual antiplatelet therapy is reasonable for up to a year after an acute coronary
syndrome.

33
Hyperlipidemia

1. What is therapeutic lifestyle change?

components of TLC as recommended by ATP III are:

2. Medications;

3. How effective and safe are combinations of lipid-lowering medications?

1. Addition of ezetimibe, niacin, or a bile acid resin to a statin often reduces serum LDL
cholesterol by an additional 20%, compared with only 6% when statin dose is
doubled
2. generally safe to use, but side effects can be additive
3. For elevations of both cholesterol and TGs, adding a fibrate lowers TG level up to
50%
4. risk of myositis and frank rhabdomyolysis increases
5. Fenofibrate appears to be significantly safer than gemfibrozil

4. Does aggressive cholesterol-lowering therapy effectively and safely reduce the risk of
coronary artery disease?
Clinical trials have repeatedly demonstrated the efficacy in secondary prevention—
1. 4S (Scandinavian Simvastatin Survival Study)
2. CARE (Cholesterol and Recurrent Events)
3. LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease)
4. HPS (Heart Protection Study)

34
 5. TNT (Treating to New Targets)
6. PROVE IT (Pravastatin or Atorvastatin Evaluation andInfection Therapy)
7. AVERT (Atorvastatin Versus Revascularization Treatment)
8. ALLIANCE (Aggressive Lipid Lowering to Alleviate New Cardiovascular
Endpoints)
9. A meta-analysis from the Cholesterol Treatment Trialists’ Collaboration suggests that
each 1-mmol/L reduction in LDL cholesterol results in an approximately 20%
reduction in the annual rate of cardiovascular disease.

5. The role of statins in the setting of primary prevention is less clear—

1. WOSCOPS (West of Scotland Coronary Prevention Study)
2. AFCAPS (Air Force Coronary Atherosclerosis
3. Prevention Study)
4. HPS (Heart Protection Study)
5. ASCOT-LLA
6. CARDS (Collaborative Atorvastatin Diabetes Study)
7. JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention
Trial Evaluating Rosuvastatin)

The major safety concerns about statin therapy are hepatotoxicity and myopathy, relatively rare

6. What is the appropriate role for niacin?

Currently unclear
1. ARBITER 6-HALTS (Arterial Biology for the Investigation of the Treatment Effects
of Reducing Cholesterol 6: HDL and LDL Treatment Strategies in Atherosclerosis)
study: among patients taking statins, niacin was superior to ezetimibe
2. AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL
Cholesterol/High Triglyceride and Impact on Global Health Outcomes) study: no
benefit to adding niacin to statin therapy.

7. What is the appropriate role for fibrates?

Somewhat unclear
1. FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study of
fenofibrate in patients with type 2 diabetes) nonsignificant 11% reduction in
cardiovascular events
2. ACCORD (Action to Control Cardiovascular Risk in Diabetes) Lipid Trial in patients
with type 2 diabetes: no reduction in cardiovascular end points when fenofibrate was
added to simvastatin.

35
8. ACC AHA 2013 guideline

9. ADA 2014 guideline for dyslipidemia drug management

1. Statin therapy should be added to lifestyle therapy, regardless of baseline lipid levels,
for diabetic patients:
1. with overt CVD
2. without CVD who are over the age of 40 years and have one or more other
CVD risk factors
1. family history of CVD
2. hypertension
3. smoking
4. dyslipidemia
5. albuminuria)
2. For lower-risk patients than the above (e.g., without overt CVD and under the age of
40 years), statin if
1. LDL cholesterol remains above 100 mg/dL
2. Multiple CVD risk factors
3. Targets:
1. individuals without overt CVD: LDL cholesterol < 100 mg/dL
2. individuals with overt CVD: LDL cholesterol < 70 mg/dL

36
 3. If drug-treated patients do not reach the above targets a reduction in LDL
cholesterol > 30–40%
4. Triglyceride levels < 150 mg/dL
5. HDL cholesterol > 40 mg/dL in men and > 50 mg/dL in women
4. Combination therapy has been shown not to provide additional cardiovascular benefit
above statin therapy alone and is not generally recommended

10. Is measurement of inflammatory markers a useful tool in CAD risk assessment?

Inflammation within an atherosclerotic plaque makes the plaque more likely to rupture
1. Highly sensitive C-reactive protein (hsCRP)
2. LDL cholesterol levels
3. indirect measure of inflammation is lipoprotein-associated phospholipase A2 (Lp-
PLA2) daraplabid: Lp-PLA2 inhibitor, are ongoing, but there is no current evidence
that lowering Lp-PLA2 will reduce cardiovascular risk

JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating
Rosuvastatin) trial showed a benefit with
1. LDL cholesterol levels lower than 130 mg/dL
2. hsCRP levels of 2.0 mg/L or less

37
1. PAD

1. Absent pulses:

1. absence of the dorsalis pedis pulse may be a anatomic variant in about 10%

2. posterior tibial pulse is present in 94% of persons

3. Hence, absence of both pedal pulses is a more specific indicator of peripheral arterial
disease

2. DSA vs MRA for PVD

1. MRA -

1. No CI

2. Collaterals well defined

2. DSA –

1. Gold standard

2. Therapeutic

3. CI – CKD

3. ABI -

1. Sn – 16%

2. Sp – 92%

3. FP – 5%

4. FN –

4. Mech of actions of drugs in PAD

1. naftidrofuryl oxalate (NICE):

1. blocks vascular and platelet 5-hydroxytryptamine 2 (5-HT2) receptors

2. 100 – 200 mg three times daily

2. cilostazol:

1. oral phosphodiesterase III inhibitor

2. direct arterial vasodilator and inhibits platelet aggregation

38
 3. 100 mg twice daily

3. Pentoxifylline:

1. oral peripheral vasodilator derived from methylxanthine

2. 400 mg TDS

4. inositol nicotinate

1. oral peripheral vasodilator that slows the release of nicotinic acid

2. 3-4 gm per day

5. supportive measures

1. Stopping smoking

2. increasing exercise

6. PAD in diabetes

1. Infra popliteal

2. Multifocal

3. Multi segmental

4. Collaterals involved

39
DFU

1. Sites
1. Neuropathic:
1. Areas most subjected to weight bearing, such as the heel, plantar metatarsal
head areas, the tips of the most prominent toes (usually the first or second),
and the tips of hammer toes
2. Areas most subjected to stress, such as the dorsal portion of hammer toes,
malleoli
2. Ischemic: over toes

2. Wagner’s classification

3. University of texas

4. Pedis

40
5. Causes of changes in diabetic foot

1. Dry foot – AN affect sweat glands

2. Hair – AN decreased blood flow

6. New adjunctive therapies

1. becaplermin gel (recombinant platelet-derived growth factor)

2. Bioengineered skin equivalents

3. maggots

4. electric

7. HIGH RISK FOOT –

1. Foot related risk factors
1. Previous foot ulcer/ amputation
2. Peripheral neuropathy – distal symmetric sensorimotor and autonomic
neuropathy
3. PAD
4. Foot deformities – Clawing of toes, prominent metatarsal heads, limited joint
mobility – abnormal foot pressures in insensate foot
5. Callus, corn, bunions
6. Poor foot care – Barefoot walking, inappropriate ill-fitting foot wear-tight
fitting shoes
2. Non-foot related risk factors
1. Diabetes > 10 yrs

41
2. Poor glycemic control
3. Other microvascular complications – Albuminuria, retinopathy
4. Smoking
5. Diminished vision

42
8. Cutaneous Manifestations of Diabetes

diabetic dermopathy
1. round to oval atrophic
hyperpigmented lesions on the
pretibial areas
2. bilateral and asymmetrical
3. edema of the papillary dermis,
thickened superficial blood vessels,
extravasation of erythrocytes, and
mild lymphocytic infiltrate
4. resolve spontaneously, leaving scars
behind
bullosis diabeticorum

Necrobiosis lipoidica diabeticorum

atrophic epidermis and granulomatous dermis
initial lesions: well-circumscribed
erythematous plaques with a depressed, waxy
telangiectatic center
Later: granulomatous lesions evolve into a
sclerotic stage of the reticular dermis and
subcutaneous fat
One-third of lesions may progress to ulcers if
predisposed to any trauma
majority of lesions occur on the pretibial
region
only 0.3 to 0.7 percent of people with diabetes
ever develop the lesions
three types of diabetic bullae
1. most common: sterile and fluid-
containing and heals without scarring
2. hemorrhagic and heals with scarrin
3. multiple nonscarring bullae on sun-
exposed, tanned skin
Eruptive xanthomas
waxy, yellow papules surrounded by an
erythematous rim
occur on the extensor surfaces and popliteal
region

4. Foot care advice

Do’s
1. Everyday wash feet with lukewarm water and soap
2. Check temperature of water with hand before using water to prevent very hot water

43
3. After wash, dry feet completely with towel expecially in between toes also
4. Inspect feet daily for redness or early ulcers
5. If feet dry, apply moisturizer cream/ coconut oil
6. Cut nails with care
7. Appropriate foot wear – Loose enough, closed on all sides, not tight, must be roomy,
reduce plantar pressures over metatarsal heads, tips of clawed toes, bony
prominences, prevent external injury, accommodate dorsal deformity, provide
stability during ADLs
8. Use cotton socks and change socks daily
9. Seek medical attention if early ulcer

Don’t
10. Never walk barefoot
11. Don’t cut corns / callus with scissor/ blade by self
12. Don’t use corn remover
13. Don’t sit/ keep feet too close to heater

44
Infections

1. Mx of emphysematous pyelonephritis

2. Infections in diabetes –
Increased with poor glycemic control
Infections more common in diabetes and more serious and infection related stress increases
sugars.
1. Infections related to diabetes , but common in general population also
1. UTIs – Bacteriuria, cystitis, pyelonephritis, perinephric abscess, renal TB,
emphysematous pyelonephritis
2. Respiratory – Pneumonia, TB
3. Soft tissue infections – Cellulitis, carbuncle, folliuculitis
4. Foot ulcer infections
5. Candidiasis – Vulvovaginitis, balanoposthitis
6. Dermatophytosis – Tinea pedis
7. Post surgery infections
2. Infections specific for diabetes, unusual in general population
1. Rhinocerebral mucormycosis –DKA
2. Emphysematous cholecystitis
3. Emphsematous pyelonephritis
4. Malignant otitis externa
3. Intervention related
1. Surgery –Post-op infections
2. Organ Tx
3. CAPD/HD

45
Charcot foot
1. Musculoskeletal manifestations
1. Fibroproliferative – trigger finger, periarthritis, cheiroarthropathy, carpal tunnel,
duptruyen’s contracture

2. Joint – charcot’s, OA, gout

3. Bone – osteoporosis, osteomyelitis

2. DD of charcot’s foot

1. Leprosy

2. Poliomyelitis

3. Syringomyelia

4. Multiple sclerosis

5. Rheumatoid arthritis

6. Alcohol abuse

7. Traumatic injury

8. Heavy metal poisoning

9. Congenital neuropathy

3. Epidemiology

1. Affects 0.8-8 % of diabetic populations

2. Incidence rates range from 3-12/1000 patients per year

3. Usually in the 5th-6th decades of life

4. 80% of patients have diabetes for at least 10 years

4. Risk factors

1. Peripheral arterial disease – protective ..... ischemia reduces inflammation

5. BPT: NPV 98% to rule out osteomyelitis; specificity 91%

6. Imaging:

46
 1. Combined leukocyte/marrow imaging is useful for determining whether or not
infection is present in a Charcot joint

2. Technetium-99m (Tc-MDP) bone scan: sensitivity % and specificity 30 % for

osteomyelitis

3. Labelled white cell scans (In-WBC) new bone formation with infection

7. DD

1. Cellulitis, trauma or sprain, acute gout, deep vein thrombosis and osteomyelitis

8. Management

1. acute COA

1. Mainstay of Rx is off-loading: allows healing of joint fractures

2. calcitonin nasal spray

3. bisphosphonates

2. chronic cases

1. Surgery is reserved for with joint instability or severe deformity

1. Achilles tendon lengthening—Contracture

2. Arthrodesis

3. Amputation

9. Pathophysiology

1. Neurovascular theory (French theory) ….. Mitchell and Charcot

1. Increased blood supply to bone is principal etiological factor

2. Arteriovenous shunting is due to autonomic neuropathy

3. Warm foot with dilated veins clinically

4. Leads to bone resorption and mechanical weakening, fractures and deformity

2. Neurotraumatic theory (German theory)….. Volkman and Virchow

1. Loss of protective sensation due to peripheral neuropathy

2. render the foot susceptible to injury

47
3. Either repeated trauma or acute trauma

4. Pathology worsens with continued weight bearing

48
10. Classification

1. Anatomical (Sanders and Frykberg, 1991)

1. Forefoot COA involving the IP and MTP joints

2. Midfoot COA involving the TMT and tarsal joints: most commonly affected area (60%)

3. Hindfoot COA, including ankle joint & calcaneum: weight distribution on walking

1. Forefoot COA better prognosis than hindfoot

1. The Rogers Bevilacqua classification for the clinical outcome of CN…….Clin

Podiatr Med Surg 2008

2. Developmental stages (Eichenholtz, 1966)

49
1. Management

50
51
Other complications
1. Deafness in diabetes –

1. Mitochondrial

2. DIMOAD

3. TRAM

4. Turner’s

2. increased risk of cancers of

1. liver

2. pancreas

3. endometrium

4. colon/rectum

5. breast

6. bladder

3. Liver disease in Diabetes

1. occurring as a consequence of diabetes mellitus
1. Glycogen deposition: poorly controlled insulin-dependent type I or type II
diabetes
2. Steatosis and nonalcoholic steatohepatitis (NASH)
3. Fibrosis and cirrhosis
4. Biliary disease, cholelithiasis, cholecystitis
5. Complications of therapy: cholestatic and necroinflammatory
2. Diabetes mellitus as a complication of liver disease
1. Hepatitis
2. Cirrhosis
3. Hepatocellular carcinoma
4. Fulminant hepatic failure
5. Postorthotopic liver transplantation
3. Liver disease occurring coincidentally with diabetes mellitus
1. Hemochromatosis
2. Glycogen storage diseases
3. Autoimmunebiliary disease

52
GDM

1. Diagnosis of GDM

2. OHA in GDM

1. metformin and acarbose are classified as category B (no evidence of risk in humans)
2. glyburide (glibenclamide) is a suitable alternative

3. Complications during delivery in DM

53
4. DETECTION AND DIAGNOSIS OF GESTATIONAL DIABETES MELLITUS

ADA 2014 Recommendations

1. Screen for undiagnosed type 2 diabetes at the first prenatal visit in those with
risk factors, using standard diagnostic criteria. Women with diabetes in the
first trimester should receive a diagnosis of overt, not gestational diabetes
2. Screen for GDM at 24–28 weeks of gestation in pregnant women not
previously known to have diabetes. International Association of Diabetes and
Pregnancy Study Groups (IADPSG) cut offs.
3. Screen women with GDM for persistent diabetes at 6–12 weeks postpartum,
using the OGTT and nonpregnancy diagnostic criteria.
4. Women with a history of GDM should have lifelong screening for the
development of diabetes or prediabetes at least every 3 years

Endocrine society 2013 Recommendations

54
5. Management – general

6. Summarize the changes in the first trimester of pregnancy.

1. promote adipose tissue accretion in early gestation
2. increased insulin sensitivity between 10 and 20 weeks of pregnancy
3. few studies have reported transient increases in insulin resistance prior to 10 weeks
4. Fasting insulin levels and glucose values are lower, and women are prone to
nocturnal hypoglycemia and ketogenesis, especially if they suffer from nausea and
vomiting
5. Deplete their glycogen stores quickly
6. Switch from carbohydrate to fat metabolism within 12 hours, often becoming
ketonemic

7. Summarize the changes in the second and third trimesters and immediate postpartum
period.
Changes shunt necessary fuels to meet the metabolic demands of the placenta and growing fetus,
which requires 80% of its energy as glucose, while maintaining euglycemia in the mother. dramatic
insulin resistance
1. 50% decrease in insulin-mediated glucose disposal (assessed by the hyperinsulinemic
euglycemic clamp technique)
2. increased hepatic gluconeogenesis
3. 200% to 300% increase in insulin secretion in late pregnancy
4. Women usually have
1. lower fasting plasma glucose levels
2. fasting hypoinsulinemia
3. presence of urinary ketones
5. glycogen stores are depleted rapidly
6. Pregnant women must transition from carbohydrate to fat metabolism earlier in the
fasting state, a phenomenon called ―accelerated starvation.‖
7. ability of insulin to suppress whole-body lipolysis is also reduced during late
pregnancy, causing free fatty acid (FFA) levels to increase
8. after delivery, insulin sensitivity returns

8. Is glucose the only fuel altered in normal pregnancy?

55
1. No. Amino acids, triglycerides, cholesterol, and FFAs are also increased
2. increase in FFAs may further accentuate the insulin resistance of pregnancy
3. maternal triglycerides and FFAs are an important source of excess fuel to the fetus and are
predictive of LGA

4. Explain the effect of the metabolic changes in pregnancy on diabetes

1. diabetes should be under tight control before conception
2. During the first trimester, nausea, increased insulin sensitivity, and accelerated
starvation may put the mother at risk for severe hypoglycemia, and thus, insulin
requirements are the least stable at this time.
3. During the first trimester, glycemic control just above the normal range (hemoglobin
A1C [HbA1C] , 7.0%) may thus be safer than ―normal

5. How do metabolic changes in pregnancy affect the management of diabetes in the second and
third trimesters?
1. After 20 weeks, peripheral insulin resistance increases insulin requirements
2. Not unusual for a pregnant woman to require two to three times as much insulin as
she did before pregnancy
3. Fasting hyperglycemia and postprandial hyperglycemia are risk factors for LGA

6. What is the risk of diabetic ketoacidosis in pregnancy?

1. DKA may occur at lower glucose levels (often referred to as ―euglycemic DKA‖)
because of
1. increased glomerular glucose filtration
2. continuous glucose utilization by the fetal-placental unit
3. greater volume of distribution of glucose due to a 30% to 40% expansion of
plasma volume
4. lower buffering capacity because of progesterone-induced respiratory
alkalosis, which results in a compensatory metabolic acidosis
5. switch from carbohydrate metabolism to lipolysis occurs

7. What causes women to get GDM?

GDM is caused by abnormalities in at least three aspects of fuel metabolism:
1. insulin resistance in fat and muscle: human placental lactogen, placental growth
hormone, tumor necrosis factor-a, and inflammatory cytokines
2. increased hepatic glucose production
3. impaired insulin secretion

8. When is a controlled exercise program contraindicated?

Women at risk for
1. preterm labor
2. vaginal bleeding
3. conditions predisposing to growth restriction
4. poorly controlled hypertension and preeclampsia
5. placental insufficiency
9. Summarize the long-term follow-up of nondiabetic women with a history of GDM.

56
 1. Women with a history of GDM should undergo a 75-g 2-hour OGTT at
approximately 6 to 12 weeks postpartum so they can be determined to be normal or to
have prediabetes (IFG, IGT) or diabetes.
2. The ADA recommends retesting every 1 to 3 years using an FBG, HbA1C
measurement or 75-g 2-hour OGTT
monitoring

1. Indications for testing for T2DM (ADA 2014)

2. blood ketone monitoring

1. Beta-Hydroxybutyrate: positive if above 1.5 mmol/L

Management – diet

Short diet history

1 cup = 150 ml cooked food, 30g; NIN Hyderabad ….. 1 cup = 200 ml

Item Kcal Carb g Prot g Fat g Fe Ca

1 roti – Poor bioavailability from
Small (20g) 70 15 2 - cereals because of phytic
Medium 25g 85 acids
Large 30 g 100

Bread slice 11/2 small, 70 15 2 -

1large
Rice ¾ cup 70 15 2 - 10mg
Ragi 100gm 350 7 3.9 400mg
Soyabean 100gm 450 40 10 300mg
Dhalia ½ cup 70 15 2 -
Dhals –All 1 cup 80(dil) 15 5 - 1.3 60mg(whole dal)
120 30mg processed dal

57
 (conc)
Milk – 1 cup 100 7 5 6 120 mg cow/100 ml
210 mg buffalo/100 ml
Human milk- 30mg/100ml
Meat/paneer/fish 30 g/ 70 - 7 5
Oil/ghee 5 ml 45
Fruits 1 40 10 - -
Vegetables 1 cup 30 5 2 -
Green leafy veg
1egg 70 10

Milk available in market

Type Fat Solids Not Fat KCalories (100 Proteins (100

ml/gm) ml/gm)
Full cream 6% 9%
Standardized milk- 4.5% 8.5%.
combining buffalo
milk and skimmed
milk
Toned 3% 8.5%
Double toned 1.5% 9%
Skimmed milk 0.5% 9%
Amul Butter 80 gm 700 0.5
Amul cheese 25 gm 300 20
Amul margarine 80 gm 700 0.2

Also take –
1. Regularity
2. Timing
3. Similar amounts
4. Veg/non-veg
5. Fat appropriate or not
6. Meal pattern

1. Food items rich in :

1. Calcium- milk, soya, ragi, dal, rajma, custard apple, cheese
2. Iron-liver, meat, sea-food, legumes, nuts, pulses, whole grain, soyabean
3. Zinc-sea food, liver meat,
4. Copper- sea food, meat, legumes, chocolate
5. Magnesium-green vegetables and sea food

58
2. Basic diet advice
1. Avoid feasts and fasts
2. Regular meal timing
3. Eat similar amounts each day for similar meals
4. Food exchanges for variety allowed as provided
5. Free foods
1. Salads, cucumber, lemon water without sugar
6. Stop
1. Sugar, sweets, chocolates, cool drinks with sugar
7. Avoid
1. Fried foods, oily foods, potatoes
8. Healthy foods
1. Green leafy vegetables, fresh vegetables
2. Whole grain foods
3. Fruits
4. Salads
5. Low fat options like skimmed milk

3. Dyslipidemia …ADA 2014

reduction of

1. saturated fat
2. trans fat
3. cholesterol intake

increase of

1. n-3 fatty acids

2. viscous fiber
3. plant stanols/sterols

4. Exercise and food

5. Glycemic index of foods

Food item Glycemic index
Glucose 100
90-99
Baked potato 80-89
Watermelon, white bread, popcorn 70-79
Sucrose, rice, ice-cream 60-69
Honey, brown rice, brown bread, potato 50-59
chips, banana, orange
40-49
Yogurt, pizza, 30-39
Beans 20-29
Peanuts 10-19
<10

6. Calories prescribed depend on weight and BMI

59
 1. Men – 900 + 10 w, w is weight in Kg
2. Women – 700 + 7 w
1. Multiply by 1.2 for sedentary, 1.4 for moderate, 1.6 for severe
3. Other formula
1. Males – 30 – 35 Kcal/kg/day
2. Females – 25 – 30 Kcal/kg/day
3. Obese – Give deficit of 500 – 1000 Kcal/kg/day = 0.5 – 1 kg weight
loss/week
4. Pregnancy
5. Lactation

7. Low cal diet – 1200- 1500 kcal/day

8. Very low cal diet < 800 kcal/day, not recommended

9. Atkins diet - Not recommended- high protein, low carb

1. a severely carbohydrate-restricted (< 20 g/day during the induction phase) diet
2. ―benign dietary ketosis,‖ which may suppresses appetite
3. other restrictions
4. studies support the idea that the Atkins Diet produces more weight loss than a low-fat
diet over 6 months but that longterm weight loss is comparable to that seen with diets
that are higher in carbohydrate and lower in fat
5. no adverse effects on blood lipid levels

10. Diet

1. RDA – 97.5% population suffices

2. EA – 100% population suffices

3. EAR – 50% population suffices

11. Artificial sweetners:

1. Isocaloric – fructose, sucrose

2. Reduced – xylitol, galicititol

3. Zero calories – aspartine, saccharin, sucralose, neotame

12. Do abnormal genes cause obesity?

1. Genetics appears to be responsible for 30% to 60% of the variance
2. These include mutations in the
1. leptin gene
2. leptin receptor
3. MC4R gene
4. brain-derived neurotrophic factor (BDNF)

60
 5. SIM-1

3. However, these mutations are quite rare, explaining less than 8% of severe early-
onset obesity.
4. Genome-wide association studies have identified more than 20 genes
5. FTO allele of this gene that is associated with weight gain is present in 15% of
humans. However, the weight gain is only 3 kg

13. What is leptin?

1. secreted exclusively by adipose tissue in direct proportion to fat mass
2. discovered in 1994 by Friedman
3. receptors located on neurons in the arcuate nucleus
4. alter the production of a number of neuropeptides
1. pro-opiomelanocortin (POMC)
2. Agouti-related peptide (AGRP).
14. What is the goal of a weight loss program?
Most effective diet, exercise, or drug treatment programs available result in roughly 5% to 10%
weight loss in most people.

15. Is a 5% to 10% reduction helpful in terms of health improvement?

Loss of 5% to 10% of body weight has been associated with improvements in health-related measures
1. lower blood pressure
2. reductions in low-density lipoprotein (LDL) cholesterol levels
3. improved
4. functional capacity
5. lower risk of diabetes
Most experts now believe that a sustained 5% to 10% weight loss a realistic goal with measurable
health benefits.

61
62
Are there any new weight loss drugs on the horizon?
A number of weight loss medications have been reviewed by the FDA:
1. glucagon-like peptide-1 (GLP-1) agonists : Exenatide 3 mg and liraglutide are being
evaluated

63
Management – insulin
1. Storage
1. At room temperature looses upto 1% potency over 30 days
2. At 2-8 C looses upto 0.1% potency over 30 days
3. Discard after first use- 3months(refrigerator); 4weeks(room temperature)
2. Needle
1. Syringe- 12mm length, 30G needle
2. Pen device- 4(Novofine plus), 5 or 8 mm length, 31/32 G needle
3. Definition of honeymoon phase;
1. Insulin less than 0.5 U/kg with HBA1C less than 7%
4. Definition of OHA failure
1. Primary
2. Secondary
5. Summarize studies evaluating optimal glycemic control to decrease chronic diabetes
complications.
1. The Diabetes Control and Complications Trial (DCCT): recent-onset type 1diabetes,
showed that improved glycemic control (hemoglobin A1C [HbA1C] < 7%
1. reduced rates of microvascular complications
2. increased rates of hypoglycemia
2. Kumamoto Study: confirmed the same with recent-onset type 2 diabete
3. United Kingdom Prospective Diabetes Study (UKPDS) confirmed the same with
recent-onset type 2 diabetes
4. long-term extensions of the DCCT and the UKPDS
1. significant reductions in cardiovascular complications with good glycemic
control
2. microvascular benefits of good glycemic control persisted for decades. Later
studies in patients with more
5. advanced type 2 diabetes (Action to Control Cardiovascular Risk in Diabetes
[ACCORD] trial
6. Action in Diabetes and Vascular Disease [ADVANCE] trial
7. VA Diabetes Trial [VADT])
1. failed to show that more aggressive glycemic targets (HbA1C , 6.0%-6.5%)
reduced cardiovascular complications
2. accord: study showed an increase in mortality
3. Rates of hypoglycemia with more aggressive glucose control were significant
in all three trials.
6. Insulin pumps:

64
7. How do you determine an initial C:I ratio?
1. Ratios are based on a patient’s total daily dose (TDD) of insulin, which usually
indicates his or her sensitivity to insulin
2. Taught to count carbohydrates before using a C:I ratio safely. Determine the C:I ratio
as follows:
1. Add up the patient’s TDD of insulin with current therapy.
2. Consider the patient’s HbA1C value (ADA target is < 7%),
frequency of hypoglycemia, and comorbidities.
3. The initial C:I is estimated by dividing 550 by the TDD
4. In clinical practice, the constant in the C:I formula may range from
350 to 550
5. adjusted on the basis of each patient’s records and is therefore only a
starting point

8. What are the standards of care for the management of diabetes mellitus?
1. HbA1C value under
1. 7.0% (ADA)
2. 6.5% (AACE)
2. low-density lipoprotein (LDL) cholesterol less than 100 mg/dL (< 70 mg/dL in high-
risk patients)
3. blood pressure lower than 130/80 mm Hg.

9. Describe the current management approach to type 1 diabetes and the role of intensive
therapy modeled by the Diabetes Control and Complications Trial (DCCT).
1. The DCCT showed a 50% reduction in clinically significant diabetic microvascular
complications
2. After an average 17 years of follow-up, the intensively treated cohort also enjoyed an
approximate 50% reduction in cardiovascular risk
3. major adverse effect of intensified control was a threefold higher risk of severe
hypoglycemia
4. intensive therapy regimen requires blood glucose monitoring four to eight times daily
with multiple daily insulin injections or an insulin pump.

10. . Is intensive diabetes therapy cost-effective?

1. The potential reduction in cost for treating diabetic complications (laser
photocoagulation, dialysis, kidney transplants, hospitalizations, and rehabilitation
following amputations) has been shown to justify the cost
2. The risk-to-benefit ratio for intensive therapy may be less favorable
1. prepubertal children
2. advanced complications
3. coronary or cerebrovascular disease.

11. What is the United Kingdom Prospective Diabetes Study (UKPDS)?

1. 5102 patients with newly diagnosed type 2 diabetes in 23 centers within the United
Kingdom between 1977 and 1991
2. followed up for an average of 10 years

65
 3. Tight blood pressure control was associated with a reduction in both microvascular
and macrovascular events
4. mean HbA1C level for the duration of the study was a strong positive predictor of all
diabetes-related end points, including death, amputation, myocardial infarction, and
stroke
5. benefits of early glucose and blood pressure control in reducing the both the
microvascular and macrovascular complications and all-cause mortality persisted 10
years after the end of the original trial.

12. What are the clinical implications of the ACCORD trial?

1. The Action to Control Cardiovascular Risk in Type 2 Diabetes (ACCORD) trial was
undertaken to address whether
1. intensive versus standard glucose control (HbA1C target , 6% vs. 7.0%-
7.9%)
2. intensive versus standard blood pressure control (systolic blood pressure ,
120 mm Hg vs. , 140 mm Hg)
3. fenofibrate versus placebo (both treatment arms were allowed statins) further
reduced cardiovascular outcomes in patients with long-standing type 2
diabetes
2. In all study arms there was no reduction in the primary outcome, which was a
composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal
stroke
3. Unexpectedly, both total mortality (hazard ratio 1.22) and cardiovascular death
(hazard ratio 1.35) were increased in the intensive glucose control arm

13. Insulin disposal

1. Major route: internalization and degradation
1. Liver: 70%
2. Skeletal muscle and fat: 15%
3. Kidney: 15%
2. 1% - renal excretion
14. What are insulin analogs?

1. Insulin analogs are recombinant proteins that are based on the structure of human insulin but
that have undergone selected amino acid substitutions, deletions, or additions.

66
2. Native human insulin (regular) exists as a molecular hexamer that must be progressively
broken down into dimers and then monomers before absorption
3. Amino acid substitutions in the carboxy-terminal region of the beta chain of insulin tend to
destabilize hexamer formation and speed the rate of absorption
1. lispro (Humalog)
2. aspart (NovoLog)
3. glulisine (Apidra)

4. long acting
1. glargine (Lantus): amino acid additions that shift the isoelectric point to promote
hexamer formation. After injection, glargine is buffered to a physiologic pH and
forms a microprecipitate that is then slowly absorbed
2. detemir (Levemir) is due to fatty acylation of the insulin molecule, which results in
albumin binding
3. Degludec, a fatty acylated insulin recently approved U.S. Food and Drug
Administration (FDA).
5. Add on therapy
1. Sulphonurea
2. Metformin
3. Pioglitazone
4. Not approved – gliptins, GLP1 analogs

Management OHA

CLASS MECHANIS MEDICATION( ACTION MONO COMMENT

M S) THERA S
PY
EFFIC
ACY
(HEMO
GLOBI
N A1C
LOWE
RING)
(%)
Sulfonylur Glipizide Closes beta-cell Increased Insulin 1.5 Hypoglycemi
eas Glimepiride KATP channels secretion channels a; weight
Glyburide gain
Meglitinid Repaglinide Closes beta-cell Increased Insulin 1.0-1.5 Expensive
es Nateglinide KATP secretion
channels
Biguanide Metformin Activates decreased Hepatic 1.5 Weight
s adenosine glucose neutral; may
monophosphate production reduce
kinase insulin

67
 requirements
Thiazolidi Pioglitazone Activates Increased Insulin 0.8-1.0 Congestive
nediones Rosiglitazone peroxisome sensitivity heart failure;
proliferator- edema; may
activated be associated
receptor-gamma with nonfatal
myocardial
infarction and
bladder
carcinoma
α- Acarbose decreased decreased Prandial 0.5-0.8 Gastrointestin
Glucosida Miglitol Intestinal glucose al side
se absorption of excursion effects:
inhibitors carbohydrates flatulence,
diarrhea
Dipeptidyl Sitagliptin Inhibit decreased Prandial 0.5-0.9 Expensive
peptidase- Saxagliptin degradation of glucose
4 Linagliptin glucagon-like excursion
inhibitors peptide-1
Bile salt Colesevelam decreased Bile Unknown App. 0.5 Expensive;
binders acid reabsorption lowers
low-density
cholesterol
and glucose
Dopamine Bromocriptine Activates Central effect and App. 0.5 Expensive;
rgic (quick release) dopamine-2 Increased dizziness;
agonists receptors insulin sensitivity nausea;
fatigue

Recently approved endocrine drugs:

1. exenatide extended-release: 2 mg once a week

2. insulin human Inhalation Powder
3. dapagliflozin
4. empagliflozin
5. Albiglutide
6. Dulaglutide
7. testosterone nasal gel

68
Mechanism of action Metformin…..Nature 2014

OHA failure
1. metformin fails: rate of around 4% per year in clinical trials
2. Secondary drug failure:

69
 1. mean blood glucose>12 mmol/L (216 mg/dl) after an initial good response of > 2 yr, after
ruling out infection and poor dietary compliance (Diabetes Care 1986)
2. 3 – 30% per year

Miscellaneous

1. Immunization Recommendations
1. Annually influenza: all above 6 months of age
2. Single dose pneumococcal polysaccharide: all above 2 years of age
1. revaccination
1. above 65 years of age whohave been immunized > 5 years ago
2. nephritic syndrome
3. chronic renal disease
4. after transplantation
3. hepatitis B vaccination

Approach to a case of Acromegaly

a. Establish history
1. Pituitary mass effects
i. Headache
ii. Vision disturbances – Field cuts
iii. Cranial nerve palsies
iv. CSF rhinorrhea – Runny discharge from nose
2. GH/IGF-1 excess – Growth excess/ metabolic features
i. Acral enlargement – Enlarging fingers and toes, increasing shoe size, tightening
of ring
ii. Before epiphyseal fusion – Gigantism – Increased linear growth
iii. Change in facial features –coarsening
iv. Skin – Increased sweating
v. Rheumatologic – Joint pains, back pain, kyphosis/stooped posture
vi. Neurologic – Carpal tunnel syndrome, proximal myopathy, peripheral neuropathy
vii. Goiter
viii. Metabolic features – High sugars, BP
ix. OSA
3. Prolactin excess – Galactorrhea in females
4. Hormonal deficiencies
i. Hypothyroidism – Cold intolerance, lethargy, constipation, periorbital puffiness,
weight gain
ii. Hypogonadism – Male – reduced libido, erectile dysfunction, reduced frequency
of shaving, decreasing testes size. Females – Amenorrhea/ Oligomenorrhea, hot
flashes
iii. Hypocortisolism – postural dizziness, vomiting, diarrhea when stress like
superimposed viral ilness
Name Age sex occupation Resident of
P/C- Headache - years
Enlargement of hands and feet - years

70
Change in facial appearance - years
History of present illness
1. Mass effects –
1. Headache – Onset, duration, progression, character, intermittent/ continuous, site/distribution,
severity/ sleep affected or not, aggravating/relieving factors, associated symptoms –vomiting
2. Visual field cuts – Diminished or blurred vision, bumping into objects, unable to see outer
aspect of eyes
3. Other cranial nerve palsies – Diplopia, drooping of eyelids
4. CSF rhinorrhea – Watery discharge from nose
2. Hormonal excess –GH/IGF-1-
 Acral enlargement – Insidious onset, slowly progressive enlargement of soft tissue thickening
and bony parts of hands and feet, swelling of fingers and toes, tightening of ring size, change
in shoe size
 Gigantism – If GH excess before epiphyseal fusion only – increased linear growth
 Coarsening of facial features – Enlarged nose, oily skin, enlarged protruding lower jaw and
chin, prominent forehead – frontal bossing, deep voice, widening of teeth, jaw malocclusion,
enlarged tongue
 Skin – excessive sweating of palms, skin tags, oily skin, hirsutism
 Musculoskeletal : Joint pains and body aches over knees and ankles, back ache, kyphosis,
scoliosis, Severe OA, any fractures, proximal myopathy
 Neurologic : Tingling sensation over hands, weakness of hand muscles, proximal myopathy,
acroparesthesia
 OSA – Disturbed sleep/ excess daytime somnolence, excessive snoring, unrefreshing sleep
with frequent waking up
 Neck swelling - Goiter
 Metabolic: DM, HTN – polyuria/ polydipsia
 Prolactin excess: Galactorrhea
 Menses
3. Hormonal deficiencies
 Hypothyroidism – Cold intolerance, lethargy, constipation, excessive sleepiness, dry skin,
weight gain
 Hypocortisolism – nausea, vomiting, postural dizziness, diarrhea, unwell during viral illness
 Hypogonadism – Males - reduced libido, erections, impotence, reduced facial hair, hot
flashes, frequency of shaving, small testes . Females - amenorrhea, galactorrhea in females.
Young individuals-onset of puberty/progression of puberty
 DI – Polyuria/polydispia
Acromegaly – Source of production
H/s/o MEN-1 – Renal calculi, pathologic fractures
PAST: DM/HTN
Rx – Outside
Indications of surgery: route/post surgery medication
Post operative complications and improvement
Recurrence of symptoms
Personal hist
Diet
Family history: Acromegaly, MEN- 1 – Parathyroid disease, renal calculi, pathologic fractures
Pancreatic malignancy- N.E.T./ Ca. breast/abdominal pain/ hypoglycemic spells/ excessive height

71
EXAMINATION
General appearance – Prognathism, frontal and supra-orbital ridge prominence, enlarged nose, oily
skin, large tongue, wide separation of teeth, deep sonorous voice, multiple skin tags, acanthosis with
acral enlargement of hands and feet, excess sweating and loss of thenar eminence
Anthropometry: Wt Ht BMI WC US/LS
Vitals BP-Postural fall in BP
Cardinal signs
Special general examn
Hypothyroid features – Bradycardia, delayed relaxation of ankle jerks
Skin – Acnathosis, skin tags, sweating of palms, pigmentation, hirustism –F-G score
Lipoma/angiofibroma/Caollagenoma
Voice- sonorous
Hands – sweating, loss of thenar eminence/oily
Feet
m.m., oral cavity, teeth – tongue(teeth indentation)
Eyes
Spine, Joints – Kyphosis, OA
Thyroid – Goiter/firm/nodules/dimensions
Testes
Body hair
Signs of active acromegaly: Sweating of palms, BP
CVS –S1S2 Normal/look for CHF, HOCM
RS- chest expansion/ shape-band chest
P/A- Hepatomegaly
CNS –
Visual acuity – R L
Visual fields by confrontation
Fundus
Other cranial nerve Palsies
Motor system – Bulk, tone, power of limbs
Carpal tunnel syndrome sensation/ wasting of thenar and hypothenar muscles
Peripheral neuropathy
Peripheral nerves

Summary:
22 year old male, with increasing height and acral enlargement, with past surgery with features of
…… present/absent

DIAGNOSIS
Acromegaly - Active/ burnt-out disease
Pituitary macroadenoma (headache, vision, cranial nerve involvement)
Pressure effects – Optic chiasma
Hypopituitarism

Plan
Specific inv-
 Biochemical confirmation:

72
 o GH suppression test
 Endosociety :
 75gm glucose
 GH 0/30/60/120 min
 AACE
 75gm glucose
 GH every 30min for 120 min
o Serum IGF-1 (anytime)
o Prolactin
 Hormonal deficiencies – FT4, TSH, 8 a.m cortisol/Stimulated cortisol, Testo post-op
 Mass effects: Perimetry
 MRI of the sella with contrast
 Others – FBS/PPBS, Na/K, X-Ray Skull, heel, hands, Ca/P
 Colonoscopy

Management:
1. Plan:(jcem 2009)

Monitoring Post- surgery(JCEM)2009:

3 months
1. GHST
2. MRI
3. Other hormonal axis

73
4. Plan: AACE 2011

Post surgery monitoring (AACE 2011)

1. Post op Day-1:
1. Fating GH if <2ng/ml long term remission
2. Week 1-2: OGTT
3. 12th week
1. OGTT(maybe); IGF-1(should)
2. MRI
3. Other hormonal axis-thyroid/gonadal

74
Questions:
1. Presenting features (pituitary tumor registery: jcem 2000)

2. DD of tall stature

3. Histopathological classification of acromegaly tumor

4. DD of pleuri hormonal secretion
1. Tumor
2. Rathke cleft cyst

75
 Predictors of mortality

5. Causes of Carpal Tunnel Syndrome:

1. Acromegaly
2. Pregnancy
3. Hypothyroidism
4. DM
5. CKD

6. Causes of ectopic GH/GHRH secretion

7. Difference between recurrence vs persistence
8. Sites of entrapment neuropathy
9. Pitfalls in diagnosis

76
10. Genes involved

77
 Approach to Cushing’s syndrome case
General approach –
iv. Symptoms of Cushing’s syndrome
v. History for differential diagnosis if required/ relevant – If no hard pointers of Cushing’s
syndrome – exogenous obesity, hypothyroidism, PCOS, metabolic syndrome
vi. Cushing’s vs Pseudo-Cushing’s – alcohol, depression/psychiatric illness.
vii. Cushing’s likely – High discriminatory features + - ACTH dep vs ACTH independent –
Pigmentation
viii. Etiology of Cushing’s syndrome – Exogenous Vs endogenous – History of steroid/
ayurvedic/ homeopathic/ over the counter medications and conditions commonly needing
steroids – joint pains/ swellings/ asthma/ skin problems/ body aches
ix. If endogenous Cushing’s syndrome – Etiology – ACTH dep- Pigmentation
a. Pituitary source – Headache/ field cuts
b. Ectopic ACTH – Lung – Cough/ expectoration/ hemoptysis/ chest pain/ dyspnea/
wheeze
c. MTC – Neck swelling/ flushing/ diarrhea
d. Pheo – Paroxysms of headache/ sweating/ palpitations/ HTN

Name Age Sex Resident of

Presenting complaints:
i. Weight gain - duration
ii. Generalized body swelling/ face/ abdomen swelling - duration
iii. Stretch marks over abdomen - duration
iv. Weakness of lower limbs - duration
v. Menstrual disturbances/ excess hair growth - duration
vi. Growth retardation/ short stature with obesity in children
History of present illness:
Symptom profile for Cushing’s syndrome –
iv. Fat gain and redistribution
a. Weight gain – Onset, duration, progression, quantify if documented, appetite. Describe as
– Insidious onset progressive weight gain of 10 Kg over 6 months despite reduced
appetite and nausea. In children – Height gain –
b. Body swelling – Onset, duration, progression, fluid vs fat, sites
Describe as – Progressive body swelling predominantly affecting face, front and back of neck and
abdomen and sparing limbs. Face gradually has become rounded with mooning of face.

v. PROTEIN CATABOLISM – High discriminatory

 Skin involvement
a. Striae – Onset, duration, progression, sites, number, width, colour
Describe as – New onset of stretch marks progressively increasing in number, size and
width and reddish/ purple in colour over abdomen, thighs, arms and chest
b. Facial redness
Describe as – Face has developed a reddish hue along with rounded appearance
c. Easy bruising without trauma, thinning of skin
d. Skin patches with itching s/o Tinea corporis

 Muscle involvement – Onset , duration, progression, type of weakness –proximal/distal,

type, other neurological history

78
 Describe as insidious onset progressive proximal weakness of lower limbs in the form of
difficulty in climbing stairs/ getting up from chair or squatting position without distal weakness
(slipping of chappals with awareness). No weakness of upper limbs. Wasting/ fasciculations/
spasticity/ sensory loss/ incordination/ bowel/bladder involvement
 Bone – Acute onset backache/ fractures(Ribs, feet, vertebrae)
vi. In children – Growth retardation, short stature with obesity important

vii. Features of excess androgens

 Menstrual disturbances/ irregularity – pattern/ LMP –Oligomenorrhea < 9 cycles/ yr or > 35

day cycles
 Hirsutism – onest, duration, progression, distribution/ sites, drug intake, hair removal,
cosmetic measures
 Acne, oily skin, seborrhea, excess sweating, body odour,
 Virilization (temporal recession of hair, deepening of voice, masculine muscle mass,
clitoromegaly, aggressive 79etaphys)
 Defeminization (breast atrophy)

viii. High blood sugars and BP– polyuria/ polydipsia/ blood sugars checked. BP- checked or not

ix. Psychiatric symptoms – Mood swings– depression/ irritability

x. Other non-specific symptoms – Fatigue, poor exercise tolerance, dyspnea, able to perform
household works/ activities of daily living or not, Renal calculi; Glaucoma

Consider D/D for Cushing’s syndrome if history not clear/ subtle only –Ask for history suggestive
of exogenous obesity/ PCOS/ hypothyroidism/ metabolic syndrome – In these conditions – No
features of protein catabolism are present and no typical fat redistribution.
Cushing’s Vs Pseudo-Cushing’s syndrome if required – alcohol excess/ depression and psychiatric
conditions,

 If Cushing’s – Assess clues for ACTH dependence – Hyper pigmentation of skin/ mouth/
nipples/ scars/ palmar creases/ knuckles

 Etiology of Cushing’s syndrome – Exogenous Vs Endogenous – History of exogenous

steroid intake/ ayurvedic/ homeopathic/ OTC medication for joint pains/ swellings/
asthma/ skin allergies

 If endogenous –

o History suggestive of pituitary lesion – Headache/ visual field defects

o Ectopic
 Lung -
 MTC – neck swelling, flushing, diarrhea, wheeze

79
  Pheo – paroxysms of headache/ palpitations/ sweating/ HTN
 Abdomen – Mass/ lump
Past History: Mostly covered under H/P/I
Past history of TB, conditions needing steroids – joints pains/ swellings/ asthma/ skin problems/ non-
specific body aches
Drug History – Detailed already mentioned in H/P/I
Evaluation for current illness outside: Investigations and treatment
Diet history: Meal pattern, calories, fat
Personal history: Occupation, Menstrual history covered, smoking alcohol
Family history: Number of siblings/ children. Family history of similar illness

SUMMARY :
38 year old lady with progressive weight gain since 6 months with predominant swelling of face and
abdomen
features of protein catabolism (in the form of striae, easy bruising, facial plethora and proximal
muscle weakness)
with/without features of excess androgens in form of (hirsutism, acne, oligomenorrhea).
Not detected to be hypertensive or diabetic
She denies exogenous steroid intake.
Possibilities at end of history:
Cushing’s syndrome – As protein catabolism and specific fat redistribution – other D/D less likely.
No features to suggest PseudoCushing’s syndrome.
No history of exogenous steroids – Cannot fully exclude exogenous, but less likely
No hyperpigmentation – Cannot diff ACTH dependent vs independent
Endogenous Cushing’s – Etiology cannot be differentiated historically – ACTH dep (pituitary,
indolent ectopic), ACTH independent (adrenal cause).
Malignant ectopic ACTH unlikely.

Examination:
General appearance –
Round face with facial plethora, acne
hirsutism/ vellus hypertrichosis,
Cervical fat accumulation, supraclavicular fullness,
central obesity with thin limbs
ecchymotic patches over limbs.

Anthropometry: Wt Kg, Ht cm, BMI Kg/m2, Waist circumference cm, WHR

Vitals: Pulse , BP , RR , Temp
Cardinal signs: Pallor, icterus, cyanosis, clubbing, edema, L’pathy
Skin –
 Thin skin, ecchymotic patches
 Striae – sites, broad violaceous, width 1-2 cm, veins at bottom
 Acanthosis
 Pigmentation – knuckles, skin, palmar creases, nipples, mucus membranes
 Tinea corporis – scaly patches with central clearing – sites

80
Features of androgenization – Acne, oily skin, hirsutism –F-G score, temporal hair recession,
clitoromegaly, deep voice
Features of defeminization – Breast atrophy
Oral cavity
Mucus membranes – Thrush
Eyes – cataracts; Glaucoma; exopthalmus
Thyroid –
Breasts –
Testes –
Joints –
Spine – Tenderness/ gibbus

SYSTEMIC EXAMINATION
Abdomen : Striae described earlier, tinea patches, scars, distension –fatty. Mass/ lump –ve. Liver,
spleen –ve. No FF.
CVS : Apex. S1S2 N. No murmur or rub
RS- Trachea central. Chest movements symmetrical. Chest expansion, Normal resonance. B/L NVBS.
No crepts or wheeze.
CNS – HMF – Mood, attention. Cranial nerves – visual acuity, fundus(disc pallor/papillodema),
visual fields by confrontation. Pupillary reflexes; V Cranial nerve; other cranial nerves
Motor system – Bulk, tone, power upper and lower limbs – especially in proximal muscles, DTRs,
sensation, cerebellar signs
SUMMARY:

FINAL DIAGNOSIS :
Cushing’s syndrome – Endogenous
Etiology –differentials – cannot differentitate clinically
 ACTH dependent – Pituitary, indolent ectopic ACTH syndrome
 ACTH independent – Adrenal causes.
 Exogenous if false history
 Other endocrine Axis
Evaluation:
 Hormonal work-up
o Screen/ confirm Cushing’s syndrome – Basal 8 a.m. cortisol to r/o exogenous. If not low
do any 2 – 24 hr UFC/ midnight cortisol/ LDDST/ ONDST/ Late night salivary cortisol.
o ACTH dependent Vs ACTH independent – Midnight/ 8 a.m ACTH
o If ACTH dependent – Pituitary Vs ectopic ACTH – Serum K+, HDDST

 Ancillary inv.
o Blood sugars – FPG/PPG/HbA1c
o Serum Na+, K+, HCO3, pH
o Hmg
o X-Ray D-L spine for occult fractures
o Ophthal R/V for cataracts/ glaucoma
o BMD
o Evaluate for infections – CXR for PTB etc.

81
 Once hormonal work-up complete- Imaging
o ACTH independent – CECT Abdomen
o ACTH dep – Pituitary MRI sella with Gd contrast, if ectopic – CECT abdomen, chest

82
Management:
1. Centrally acting drugs

2. Adrenolytic drugs

83
Questions:
 Exogenous vs endogenous Cushing’s syndrome

Feature Exogenous – ACTH low Endogenous – ACTH dep

History Exogenous steroid intake++ No history of exogenous
steroid intake
Hyperpigmentation --- Maybe +ve
Androgen excess- Hirsutism, Absent as reduced ACTH If + ve –suggestive
amenorrhea reduces adrenal androgens
virilization

HTN --. Reduced + suggestive

mineralcorticoids
BMD More reduced Maybe normal if high adrenal
androgens
Specific features Bone – Osteonecrosis of If present-likely
femoral heads, osteoporosis Features of androgen excess,
Eyes – Glaucoma, post hyperpigmentation and HTN,
subscapular cataracts, BIH plethora straie/ purpura/
GIT – Peptic ulcer, erectile dysfunction
pancreatitis
Test Basal 8 a.m. cortisol ONDST, LDDST, UFC 2,
Midnight serum cortisol, late
night salivary cortisol
 High discriminatory features of Cushing’s syndrome- Protein catabolism features
a. Easy bruising with no obvious trauma
b. Thin skin
c. Broad reddish purple striae > 1 cm
d. Facial plethora
e. Proximal muscle weakness
f. Unexplained osteoporosis
g. Obesity with growth retardation in children

 Why fat redistribution in Cushing’s

 Higher GR expression in visceral and abdominal fat
 Higher 11 b OH steroid DH 1 activity in visceral fat – Increased conversion of
cortisone to cortisol

 Why HTN in Cushing’s

a) Increased permissive action for endogenous vasoconstrictors – Catecholamines,
Angiotensin 2, Vasopressin
b) Increased DOC – Higher MC action
c) Increased cardiac output
d) Increased angiotensinogen 1 production from liver

84
 Why hypokalemia
i) Increased cortisol in ectopic ACTH overwhelms renal 11b OH steroid DH 2 activity – High
cortisol in kidneys (low cortisone) –acts on MC

 Hirsutism D/D
i) Idiopathic
ii) Racial variation
iii) Exogenous androgens
iv) High androgens –Ovarian PCOS – Obese, acanthosis, oligomenorrhea
v) High androgens – Neoplasm – Adrenal or ovarian cause
vi) Late onset CAH or NCCAH
vii) Other endocrinopathies – Hypothyroidism, Prolactinoma, acromegaly

 Childhood Cushing’s syndrome – Etiology

 D/D of Childhood Cushing’s syndrome – Obesity with short stature –

o Hypothyroidism
o genetic syndromes of obesity and short stature like Prader willi, Lawrence Moon Biedl
o GH deficiency – GHD/ insensitivity – abdominal obesity
o Craniopharyngioma
o AHO phenotype

 Differentiate Pituitary Vs ectopic ACTH

1. ACTH levels higher in ectopic
2. Hypokalemia – Ectopic
3. Male sex – ectopic
4. If malignant – present like adrenal insufficiency – hyperpigmentation, prox myopathy,
hypokalemia, met alkalosis

85
 Salivary cortisol

 Indications of IPSS

 Endocrine causes of palpitation

1. Hyperthyroidism
2. Pheochromocytoma

 Causes of hyperpigmentation
1. Addisons disease
2. Vit B12 deficiency
3. Haemochromatosis
 Causes of waxing and waning of hyperpigmentation
 Causes of straie
1. Garvidarum-pregnancy
2. Rapid weight gain or weight loss
3. Cushings syndrome
 Classical components of pheochromocytoma-paroxyms
 Causes of bilateral optic atrophy
1. Optic nerve deficiency
2. Radiotherapy
3. Vit B12 deficiency
1. Causes of Multiple pituitary Axis overactivity
1. Ratke’s cleft cyst
2. Mccune Albright
1. Risk factors for Nelson Syndrome
1. Tumor Remanant
2. Pituitary Macroadenoma
3. Non-compliance to therapy
20. Anisocormia D/D
21. Incidence of Cushing’s syndrome(Jorgensen, JCEM 2001)
1. C. Syndrome: 2-10/ Million Per year
2. Adrenal neoplasm: 2/ million per year
3. A.C.C : 1/million per year
22. Age distribution:
1. ACC: childhood then 45-55 yrs(Bimodal)
2. Adrenal adenoma: 25-45 yrs
3. PPNAD: 5-25 yrs
4. AIMAH: above 50 yrs
23. Morbidity in Cushings syndrome
1. 5 yr survival- 50%
2. Due to: CVA, infections
24. Features that increase suspicion of ACC/ Ectopic ACTH
1. Extreme muscle atrophy
2. Hypokalemia

86
3. Alkalosis
4. Hypercalcemia
5. Sudden onset DM
6. Virilization(ACC)
25. Common sites of ACC mets
1. Liver
2. Lung
3. Retroperitoneal l.node mets
4. Bone
26. Hypoglycaemia in Cushing’s:
Extensive hepatic mets
27. Cushing’s syndrome during pregnancy
LH dependant AIMAH

87
 Approach to thyroid case
Name Age Sex Occupation Place of residence – Goiter belt of India/UP or not
History of neck swelling front aspect of neck
1. Onset, duration, progression, rate of growth
2. Unilateral or both sides
3. Any recent rapid growth
4. Associated pain/ discomfort – neck, ears, jaw/ discomfort/ fever
5. Temporal correlation of goiter with thyrotoxicosis if present
6. Other swellings –Neck LN swellings, bony swellings/ back ache
Pressure symptoms
1. Difficulty in breathing
2. Stridor
3. Dysphagia to solids/ liquids
4. Dry cough on lying down
5. Hoarseness of voice
6. Face and neck swelling/ prominent veins
Thyroid function
1. Hypothyroidism – Weight gain despite poor appetite/ cold intolerance/ constipation/ puffiness
of face, around eyes/ lethargy/ slowness of activities/ change in voice/ excess sleepiness/
proximal myopathy/ menorrhagia/ coarse dry skin/ loss of hair especially lat 2/3 of eyebrows/
reduced memory/ academic deterioration and growth retardation in children
2. Thyrotoxicosis –
iv. Unitentional weight loss – quantify/ increased appetite. Ask for other
important causes of weight loss if needed
v. Heat intolerance and preference for cold, increased sweating
vi. CNS : tremors/ nervousness/ anxiety/ irritability/ proximal myopathy/
anxiety/ insomnia
vii. CVS: palpitations, dyspnea on exertion
viii. GIT: diarrhea/increased stool frequency
ix. Others: fatigue/ back ache – vert fracture/ menses
x.
History suggestive of metastasis – Bony swellings, neck LN swellings
MTC – diarrhea, wheeze, flushing
Eyes –
1. Thyrotoxicosis related: staring due to lid retraction, prominent eyes
2. Inflammation: grittiness, foreign body sensation, excess watering, photophobia, redness,
swelling, pain on eye movts or behind eyes
3. Protruding eye balls, double vision, (intermittent/consistent)diminished vision, blind spots,
factors in proving vision (blinking, lowering one eye)
4. Past eye history: past surgery, previous ocular medications
Skin – Dermopathy – plaques, hyperpigmentation
Deafness in children
Iodized salt
Past: Neck irradiation
Drugs – RAI ablation, amiodarone, Li, IFN
Iodine belt or not – goiter/ cretinism in community, flooding and leaching of soil
Family history of thyroid illness/ history of cretinism
Smoking – especially in GD/GO

88
SUMMARY:

Examination
General appearance – Hypothyroid – Puffiness of face esp around eyes, dry coarse skin, hoarse
voice, madarosis, goiter, expressionless face, dull
Thyrotoxicosis – Thin built emaciated patient, anxious, jittery with excess sweating, staring
protruding eyes with periorbital edema, diffuse large goiter, tremors

Wt Ht BMI
Vitals
Cardinal signs – Pa/ I/ Clubbing – thyroid acropachy/ Cy/ L’pathy/ PE

Thyroid function
1. Pulse
2. Tremors – fine distal, outstretched hands
3. Sweating – Palms
4. Delayed relaxation of ankle jerks
5. Weight/ BMI
6. Voice –hoarse

Eyes
1. Visual acuity
1. Snellens chart
2. Color vision
2. Pupils
3. Eyelids
1. Lid retraction (Dalrymple’s sign)
2. Lid lag (Von Graefe’s sign)
3. Infrequent blinking (Stellwag’s sign)
4. sclera seen inferiorly
5. No forehead wrinkles → Joffroy’s sign
6. Difficulty everting the upper eyelids in thyrotoxicosis → Gifford’s sign
7. Conjuctiva and cornea
1. Conjuctival congestion and edema
2. Corneal ulcers, diminished vision
3. Exopthalmometry
1. Exophthalmos
2. Actual bulge (Naffziger’s method)
3. Ocular motility
1. Mobius’s sign: Note convergence of eye by holding finger one meter from the eyes
and ask patient to look, then slowly move finger towards midpoint of eyebrows of the
patient, the patient can’t converge the eyes in exophthalmos
2. Opthalmoplegia
4. Progressive Exophthalmus:
1. Further bulging of eyeballs
2. Ophthalmoplegia

89
3. Signs of GO – Soft tissue signs – redness, edema, pain, chemosis
4. Exophthalmos – unilateral/ bilateral, diplopia, corneal erosions, decreased visual acuity,
reduced extraocular movts, lagophthalmos, exposure keratitis
5. Disease activity
1. Clinical activity score
2. Severity

Skin
6. Pretibial myxedema
7. Hyperpigmentation
8. Hypothyroid – Coarse dry skin
9. Cutaneous licen amyloidoisis – MEN 2 A
10. Mucosal neuromas – MEN 2 B

Nails – thyropachy

Skull, Spine

Thyroid examination-
1) Inspection: make the patient sit on stool with neck slightly hyperextended. Asking the
patient to swallow makes the thyroid move prominent for inspection
a. Goiter – Size, mobile upwards with swallowing
i. Diffuse or not, symmetrical/ asymmetrical
ii. Surface – nodular/ smooth
iii. Lower border visible or not
b. Neck/ dilated anterior chest wall veins indicate retrosternal extension
c. Face plethora
d. Scars
e. Skin over swelling –
i. • Redness and edema → suggestive of inflammation
ii. • Scar of previous surgery
iii. • Sinuses → thyroglossal fistula
iv. • Dilated vein

90
 f. LNs
g. Pemberton sign /Arm-raising test: Raise both arms till shoulders touch ears. This
narrows thoracic inlet further in a patient with already narrow thoracic inlet due
to retrosternal goiter.
i. Congestion and venous engorgement of the face
ii. Respiratory distress
iii. Rare – syncope
h. Pulsations
i. Trachea
j. Tongue – posterior dorsum
k. Movement with protrusion of tongue /Upward movement on deglutition. Thyroid
swelling moves in deglutition but we have other condition where swelling moves
in deglutition:
i. Thyroglossal cyst
ii. Pre-tracheal Lymph Nodes
iii. Subhyoid bursa
iv. Extrinsic carcinoma of larynx
But lipoma does NOT move during deglutition because it is not attached to the pre-tracheal fascia
If swelling is a nodule which is close to the midline we must test its upward movement on protrusion
of the tongue.
Thyroglossal cyst and Thyroglossal fistula move upwards with tongue protrusion.

2) Palpation
a. Methods –
i. From behind – Both thumbs on occiput, palpate with 4 fingers
ii. Pizzilo method – Patient’s hands behind occiput, extend neck backwards
– Use for short neck in obese
iii. Lahey’s method – Push thyroid to opposite side from front to palpate
each lobe
iv. Crile’s method – Feel with thumb while patient swallows
b. Goiter –
i. Shape
ii. Size in relation to normal, extent
iii. Right lobe , left lobe, isthmus, symmetrical/not, diffuse or not
1. Normal thyroid lobe has same size in frontal projection of
terminal phalanx of the patient’s thumb
c. Borders in relation to the sternomastoid muscle and the suprasternal notch
i. Temperature
ii. Surface – smooth/ lobulated/ bosselated/ nodular
1. MNG – 2 or more areas of nodularity palpable
iii. Nodules – shape, size, position, consistency, extent
iv. Pyramidal lobe
v. Consistency – uniformly / variable firm
1. Normal - > adipose tissue , < muscle
2. Firm, diffuse, symmetrical – Hashimoto’s thyroiditis
3. Soft – Dyshormonogenesis
4. Hard – malignancy
vi. Tenderness

91
 vii. Mobility – vertical while swallowing, horizontal
viii. Lower border palpable or not
ix. Thrill
d. Trachea – stridor, Kocher’s test
Kocher’s test for scabbard trachea : Ask patient to take heavy deep breath and open mouth and
compress swelling from both sides, if there is hoarseness of voice (indicate narrowing of trachea). It is
seen in carcinoma and multinodular goiter
3) Carotids – displaced or absent: for Berry’s sign (for obliteration of carotid pulsation): in a
benign goter, carotid pulse is well felt, though displaced backward. In malignant goiter,
carotid pulse is weak or absent

4) LNs – deep cervical/ supraclavicular LN

5) Horner’s
6) Voice
7) Percussion – Retrosternal percussion
8) Auscultation – Bruit at superior border of thyroid – Graves’ disease, dyshormonogenesis,
hyperplastic nodule of MNG

Systemic Examination:

RS:
CVS: Non-palpable Apex (pericarditis effusion)
PA:
CNS:
1. HMF
2. Cr nrves
3. Motor
4. Sensation
5. Cerebellum
Ataxia: hypothyroidism
Bulk: increase in calf/tongue/shoulders,
Wasting of thenar/hypothenar muscles(carpal tunnel syndrome)
Tone:
Power: weakness(Type 2 Type1)
Reflexes: Delayed contractility
Delayed relaxation
Others:
1. Myokymia (undulatory muscle spasms-similarly to worms crawl)
2. Pseudomyotomia (slow relaxation after voluntary muscle contraction)
3. Myoedema (mounding of muscle tissue after light stroke)

Syndromes:
1. Hoffman (Adults)
1. Weakness/ cramps/pain
2. Increases muscle enzymes
3. Pseudohypertrophy/ Pseudomyotonia
2. Kocher-Debre-Semelaigne Syndrome

92
 1. Infants with creteinism

Diagnosis:
Clinical presentation of thyroid disease
1. Disorders of hormone production
a. Reduced – hypothyroidism
b. Increased - Thyrotoxicosis
2. Local symptoms in neck
a. Goiter
b. Pain
c. Pressure symptoms
3. Metastasis
4. Extrathyroidal manifestations in Graves’ disease
a. Ophthalmopathy
b. Dermopathy

Investigations:
1. For hyperthyroidism
2. For MNG
3. For STN
Management:
1. Hyperthyroidism
1. Steroids to prevent GO when RIA is planned: ATA 2011

2. GO severity: ATA 2011

3. Grave’s disease in pregnancy: ATA 2011

93
 4. Subclinical : ATA 2011

5. Beta blockade: ATA 2011

2. Thyroid storm
1. Diagnosis : ATA 2011

94
 2. Management: ATA 2011

3. MNG
4. STN

95
 Questions: hashimoto’s
Management of subclinical hypothyroidism

Grave’s

1. prevalence
1. grave’s disease
2. grave’s opthalmopathy: 28% (SGPGIMS – Indian J Med Res 2014 )

2. What is the outcome of radioiodine treatment?

1. Euthyroidism is not achieved for months after treatment
2. Hypothyroidism, the only serious side effect, is dose dependent
3. rate of 3% per year
4. 50% of patients at 10 years
5. 100% at 25 years

3. What are the indications for thyroidectomy for hyperthyroidism?

1. Patients who are pregnant are difficult to treat medically.
2. Patients with large goiter and low radioiodine uptake.
3. Children.
4. Noncompliant patients.
5. Patients with nodules suspected to be cancer (cold).
6. Patients with compression of the trachea or esophagus.
7. Patients with cosmetic concerns.
8. Patients with ophthalmopathy.
9. Allergy or significant side effects to ATDs.
4. What is the regimen of radioiodine treatment?
1. Grave’s disease :10 to 15 mCi for
2. TMNG: 25 to 30 mCi
3. Older patients and patients with significant comorbidity: ATDs before radioiodine
4. significant eye disease and smokers: corticosteroids before radioiodine

96
 5. Pregnancy is an absolute contraindication
6. Avoid pregnancy for 6 months after treatment

1. Drug induced thyrotoxicosis: ATA 2011

2. Causes of firm smooth thyroid gland

1. Toxic
1. Hashitoxicosis
2. Post RIA
3. Post ATDs
4. Silent thyroiditis
2. Non toxic
1. Hashmoto’s
1. Goiter: false positive – Overestimation of the size of the thyroid
1. A more easily palpable thyroid in a thin patient with less overriding tissue
2. A higher placed thyroid (normal variant)
3. A long, curving neck that enhances prominence and palpation of the gland
(Modigliani drawing)
4. Lesion behind thyroid, pressing it forward
5. Enlargement of adjacent structure, mistaken for thyroid
2. Goiter: false negative – Underestimation of the size of the thyroid
1. Inadequate physical examination (most common cause)
2. Short thick neck in patients, seen most commonly in the obese, elderly or pts with
COPD.
3. Atypical placement of thyroid ( retrosternal or lateral placement of lobes)
3. Etiology
1. Hypothyroidism
1. chronic autoimmune thyroiditis (Hashimoto’s thyroiditis)
2. radioactive idine therapy for hyperthyroidism
3. thyroid surgery
2. Hyperthyroidism
1. Graves‖ Diseases

97
 2. toxic nodular goiter (TNG)
3. toxic adenoma
4. postpartum thyroiditis(silent and painless)
5. subacute thyroiditis(de quervain’s)
6. exogenous thyroid hormone ingestion.
7. Hashimoto’s
8. Congenital hyperthyroidism
9. Pregnancy (gestational); GTD
10. IIT
11. TSH adenoma
12. Stuma ovarii

4. Causes of tender thyroid:

1. Acute suppurative thyroiditis
2. de Quervain thyroiditis (the commonest cause of a painful thyroid)
3. acute hemorrhage into a cyst or thyroid nodule
4. rapidly enlarging thyroid carcinoma(anaplastic)
5. radiation thyroiditis
6. Hashimoto’s (very rare)

1. NOSPECS

1. N

2. O

3. S

4. P

5. E

6. C

7. S

1. Indications of RIA

2. Contra indications of RIA

3. Steps of surgery – order

98
 1. After 6 months of inactivity

2.

4. Difference B/W grave’s vs subacute thyroiditis

Grave’s subacute thyroiditis
T3 T4 ratio > 20 < 20

5. IFN a related endocrine diseases

6. DD of hyperthyroidism

1. No 99etaph

1. Exogeneous LT4

2. Iodine excess

3. Struma ovarii

2. Diffuse goiter

1. Graves disease

2. Thyroiditis

1. Silent (50%-goitre)firm

2. Subacute-firm/hard

3. FNAH

4. TSH adenoma

5. T4 resistance

6. Large tumor

3. Nodular goiter

1. Multinodular 99etaph

2. AFTN

3. MAS

4. Hyperfunctioning Ca

99
7. DD of Euthyroid goiter

1. Diffuse goiter

1. Endemic goiter

2. Colloid goiter

3. Goitrogen

2. Nodular goiter

1. Longstanding hashimotos-firm

2. MNG

3. Colloid nodule

4. Thyroid malignancy

5. Cyst

6. Metastasis

8. Role of selenium in graves disease

9. Pathogenesis in graves disease

10. Indian data on grave’s: proptosis is significant if

1. 20 mm = india
2. 18 mm = Chinese

3.

11. DD of Proptosis
12. Difference B/W silent vs subacute thyroiditis
Silent subacute thyroiditis
ESR High Very high
Pain Absent Present
Long Term Hypothyroidism(50%) Euthyroid(majority)
Pathology Lymphocytic infiltration Giant cells, granuloma
Recurrence Common Rare
Ab Anti-TPO(very common) Approx. 50% transient

100
 MNG
1. What surgeon won the Nobel Prize for his work with thyroid disease?
Theodor Kocher 1909
2. Goitre WHO classification
1. grade 0, no goiter
2. grade 1, palpable but not visible
3. grade 2, clearly visible with the neck in normal position
3. principal indicators of an effective salt iodinization programme
1. household availability of iodine through edible salt
2. median urinary iodine concentration (UIC), highly sensitive to recent changes in
iodine intake
3. Goitre rate that reflects thyroid size is a poor secondary indicator
4. Salt iodination India
1. National Family Health Survey-III
1. 50% of households: adequately iodized salt (iodine content >15 ppm)
2. 25% non-iodized salt

5. IDD in north india; Gonda study….Public Health Nutrition:2009

1. 101etaph prevalence
1. 70 % - 1982
2. 30 %- 2007
2. 35% of villages still had very high endemicity of 101etaph (101etaph prevalence > 30
%)
3. Household Iodine consumption from salt
1. 25 % (<5 ppm)
2. 55% (5–15 ppm)
4. Causes of persisting iodine-deficiency disorders.
1. Poor coverage
2. use of unpackaged crystal salt with inadequate iodine
3. washing of salt before use by 90% of rural households
4. supply of larger crystalline salt with higher Ca content and poor iodine
retention
6. urine collection:
1. preserved in a plastic bottle containing a few drops of toluene
2. Sandell–Koltoff reaction
7. Iodine content of salt
1. estimated by iodometric titration
2. expressed in parts per million
3. Iodate
1. Highly stable in humid conditions
2. Reduced in stomach to iodide
8. 12% -- Kerala goiter recent

STN
1. DD of STN

101
2. What is the prevalence of thyroid nodules and cancer?
1. 4 times more common in females than in males
2. palpation 5%
3. ultrasound (US) 35%
4. autopsy 50%
5. After exposure to radiation, nodules: 2% annually, reaching a peak at 25 years
6. At autopsy: occult papillary cancer (<1.0 cm)- Up to 35%
3. What features of the history and physical examination indicate a higher risk of cancer?
1. extremes of age
2. males
3. Rapid growth
4. associated symptoms of local invasion (e.g., hoarseness, dysphagia)
5. Fixation to adjacentstructures
6. radiation exposure
7. hard nodules
8. enlarged lymph nodes
9. family history
1. medullary
2. papillary thyroid cancer
3. Gardner’s syndrome (i.e., familial polyposis) increases the risk of cancer.

1. Thyroid Cancer : 95% presents as a thyroid nodule or neck mass.

In order of decreasing frequency and increasing invasiveness
1. papillary (75%) – most common and least aggressive
2. follicular (15%)
3. medullary (5%)
2. DD of neck mass with bone nodules
a. FTC – 15% of DTC, bone mets 10 – 20%
b. PTC – 40% of DTC, bone mets 1 – 10%
c. MTC –
d. PhPT with brown tumor

3. DD of neck mass, bone nodules and diarrhea

a. MTC with mets

102
b. MEN 1 – PhPT, brown tumor with VIPoma
Genetics of MTC
Sporadic – 25% somatic mutation RET
7 % germline mutation RET

4. Mets in MTC
If palpable MTC; > 80% LN mets ipsilateral, 40% contralateral
Vasc mets – lung, liver
Bone mets – lytic

5. Investigations for MTC

FNAC: Amyloid, calcification
Stain – CT, CEA, CgA
CT, CEA
Skeletal scintigraphy
Xray neck – calcification
Thyroid scan – cold nodules
Urine metaneprines

6. Management of MTC
1. Localized – cure possible, total thyroidiectoomy with central lymph node (level 6) dissection.
2. Mets to neck – cure may be possible
3. Mets beyond neck – no cure
Levels of cervical lymph nodes
Prevalence of thyroid nodules – 0 at 15 yr and 50% at 60 yrs

4. FNAC

1. Sn – 87%

2. Sp – 53%

3. NPV – 94%

5. Molecular markers in FNAC

1. Ca – galactin 3, braf, ret ptc, ras, TPO

6. Risk factor for AFTN

1. Female
2. Age>60yrs
3. Size> 2.5cm
7. Indications of FNAC

1. Euthyroid nodule

2. Features suggestive of malignancy

103
8. Diarrhea in MTC
1. Non-voluminous
2. 30% of cases
3. Due to excess of ? Calcitonin/serotonin/VIP

9. Drugs in MTC

10. DD of flushing
1. Carcinoid
2. Pheochromocytoma
3. MTC
4. Mastocytosis
5. Alcohol
6. RCC
7. Migraine
8. M. sclerosis
9. Horner’s Syndrome
10. Climatic
11. Significance hormonal evaluation in MTC
a. CT –
i. directly correlate with tumor volume
ii. falling values may indicate de differentiation
iii. other tumors – breast, prostrate, SCC, pheocromocytoma
b. CEA –
i. Less sort term variability
ii. Made in GI and liver also
1. Elevated in smokers
c. ACTH – 5% of EAS

104
Approach to a thyroid case in children
Presentation of Congenital Hypothyroidism
At birth
1. Post-maturity
2. Macrosomia
3. Macrocephaly
4. Open posterior fontanelle
5. Absent Os knee
During infancy
1. poor feeding
2. Hypotonia
3. Lethargy
4. Hypothermia
5. Constipation
6. Macroglossia
7. Prolonged jaundice
8. Umbilical hernia
9. Abdominal distension
10. Dry skin
11. Hoarse cry
12. Myxedematous appearance

Syndromic association
1. Cleft palate, bifid epiglotitis, kinky hair (TTF-2/Fox1-Lazarus bonfort)
2. Pulmonary hypolplasia, ataxia, athetosis (TTF1/NKX2-1)
3. Renal defect (Pax-8)
4. Cardiac defect (NKX2-5)

Questions
1. Neonatal screening programme….IP2014
Age-related cut-offs for serum TSH was used for immediate venous TSH and T4:
1. >34 mIU/L during 24-48 hours of life
2. >20mIU/L after 48 hours for repeat filter paper TSH
3. >40 mIU/L at any age

2. Approach to etiological disease

1. Usg appearance of thyroid
1. Absent/dysgenetic- Thyroid scan; to detect athyrosis or ectopic gland
2. Normal- thyroid scan; to detect
1. No uptake in thyroid-TSH binding inhibiting immunoglobulin
2. No uptake in thyroid, salivary and gastric gland-NIS defect
3. Normal uptake-peripheral destruction
3. Goitrous-per chlorate discharge test for dyshormonogenesis
2. X-ray knee-
3. maternal antibody
4. maternal urinary iodine
5. maternal antithyroid drugs

105
3. Clinical approach to hypothyroidism in child
1. no goiter
1. dysgenetic
2. ectopic
3. central
4. post surgery
5. post radiation
6. peripheral
7. atrophic thyroiditis
8. long standing hashimotos
2. diffuse goiter
1. thyroiditis
2. goitrogen
3. dyshormonogenesis
4. TBG deficiency
5. T4 resistance
6. Hashimotos
3. Nodular goitee
1. long standing hashimotos
4. Incidence of Congenital Hypothyroidism
1. 1:3500 live births
5. Congenital Hypothyroidism etiology:
6. Decreased synthesis
1. Thyroid dysgenesis(85%)
1. Athyreosis(30%)FOXE1, NKX2-5
2. Thyroid ectopy(40%) FOXE1, NKX2-5
3. Thyroid hypoplasia(30%)NKX2-1, TSHR, PAX8
2. Dyshormonogenesis(15%)
1. NIS:goiter
2. TPD: goiter
3. DUOX1, DUOX2: no goiter
4. DUOX A2: goiter
5. TG: goiter
6. Pendrin: goiter
7. IYD: no goiter, variable age
3. Hyporesponsiveness to TSH(small gland)
1. TSHR
2. GSα
7. Central congenital hypothyroidism
8. Persistent congenital hypothyroidism
9. Hemiagenesis:
10. Absent left lobe in almost all cases

106
 Approach to a case of hirsuitism
History
Presenting complaints:

A) Increased hair growth

a. onset, duration, progression, distribution/ sites, drug intake, hair removal, cosmetic
measures growth began at puberty or after

b. Rapid onset of hirsutism

c. Progression of hirsutism despite treatment

d. Hair removal measures have already been tried

e. Acne, oily skin, seborrhea, excess sweating, body odour,

f. Virilization (temporal recession of hair, deepening of voice, masculine muscle mass,

clitoromegaly, aggressive 107etaphys)

g. Defeminization (breast atrophy)

h. Palpable abdominal or pelvic mass

i. Time of puberty and menarche

B) Irregular menses – Menstrual disturbances/ irregularity – pattern/ LMP –Oligomenorrhea < 9

cycles/ yr or > 35 day cycles
C) Infertility

Reproductive history should also be obtained

D) Insulin resistance

On enquiry:

1. For CAH-

1. Hyperpigmentation

2. salt craving, adrenal crisis

3. hypertension

2. for cushings: straie, easy bruisability, back pain

3. for acromegaly: acral enlargement

4. for hyperprolactinemia: galactorrhea

107
 5. complaints suggestive of hypothyroidism or hyperthyroidism

Medication history

Family history

4 congenital adrenal hyperplasia, unknown cause of death in young child

5 hair patterns of family members (if possible) because idiopathic hirsutism is often familial

6 type 2 diabetes mellitus

Personal history:

Menarche at 12 years

Summary
23 yr old female
Rapid onset of virilization
With positive findings of----
With absent ----
Provisional diagnosis:
1. Virilization
a. PCOS
b. LOCAH
c. Adrenal tumor
d. Ovarian tumor
e. Idiopathic hyperadrogenism
Examination
Acanthosis nigricans

Anthropometry: Wt Ht BMI WC Central obesity

Vitals BP-Postural fall in BP

Cardinal signs
Features of androgenization:

a) Deep voice

b) Acne

c) oily skin

108
 d) hirsutism – Mod FGS score

e) Temporal hair recession

f) loss of typical female body contours

g) clitoromegaly

Features of defeminization – Breast atrophy

Increased hand and foot size, mandibular enlargement, coarse facial features

Central obesity, moon facies, purple skin striae, proximal muscle weakness

palpable abdominal or pelvic mass

Galactorrhea

Thyroid dysfunction

Systemic examination –
Abdomen : Striae described earlier, tinea patches, scars, distension –fatty. Mass/ lump –ve. Liver,
spleen –ve. No FF.

abdominal and bimanual examination should be performed to identify palpable tumors, pregnancy

CVS : Apex. S1S2 N. No murmur or rub

RS- Trachea central. Chest movements symmetrical. Normal resonance. B/L NVBS. No crepts or
wheeze.
CNS – HMF – Mood, attention. Cranial nerves – visual acuity, fundus, visual fields by confrontation.
Motor system – Bulk, tone, power upper and lower limbs – especially in proximal muscles, DTRs,
sensation, cerebellar signs
Summary
23 yr old female
Rapid onset of virilization
With positive findings of----
With absent ----
Final diagnosis:
1. Virilization
1. PCOS
2. LOCAH
3. Adrenal tumor
4. Ovarian tumor
5. Ovarian hyperthecosis

109
6. Idiopathic hyperadrogenism

7. Hirsutism
1. PCOS
2. LOCAH
3. Adrenal tumor
4. Ovarian tumor
5. Ovarian hyperthecosis
6. Insulin resistance
7. Cushings syndrome
8. Hyper/hypothyroidism
9. Idiopathic hyperadrogenism / hirsuitism
10. Drug induced
11.
Investigations
Hormonal
1. total testosterone level greater than 200 ng per dL (6.94 nmol per L) should prompt evaluation
for an androgen-secreting tumor ---- adrenal or ovarian
2. DHEAS --- adrenal origin
3. 17-hydroxyprogesterone level ---- CAH
4. GHST
5. thyroid function tests
6. prolactin level
7. ONDST
Ancillary investigations:
1. Blood sugar fasting and PP
Imaging:
1. USG pelvis
1. PCOD- greater than 12 follicles each 2-9 mm or ovarian size > 10mm
2. CECT abdomen- to look for adrenal or ovarian tumor

Management:
a) mild hirsutism and normal menses do not require laboratory workup and can be
treated empirically

b) avoiding preparations containing levonorgestrel, the most androgenic progestin

c) prefer progestins –
1. with low androgenicity
1. norgestimate
2. desogestrel
2. progestins that exhibit antiandrogenic activity
1. drospirenone – yasmin (drosperone 3mg with E2 30mcg)
2. CPA
d) Eflornithine is an irreversible inhibitor of ornithine decarboxylase, an enzyme that
catalyzes the rate-limiting step for follicular polyamine synthesis, which is necessary
for hair growth. A topical preparation, eflornithine hydrochloride cream 13.9%
(Vaniqa), is approved in many countries for the treatment of unwanted facial hair in
women. Eflornithine does not remove hair but acts to reduce the rate of hair growth.

110
 e) Finasteride
f) Spironolactone
g) Doses (jcem 2008)

1. Photoelipation (jcem 2008)

111
Questions:
1. Prevalence:
a. Approximately 7 percent of women
b. Women of 18-25 years from Lucknow, is 3.7% (Indian J Endocrinol Metab. 2012)

2. Ferriman-Gallwey scale limitations:

a. subjective nature
b. failure to account for all androgenic areas (e.g., sideburns, buttocks)
c. focal hirsutism
d. ongoing use of cosmetic measures
e. lack of normative data on other populations
f. effect on patient well-being.

(A) Other hyperandrogenemia manifestions: acne, seborrhea, menstrual dysfunction, or alopeci

(B) PCOS diagnosis

112
(C) Medications causing hirsuitism:

113
(D) Approach:

114
(E) Causes

115
 Approach to Gynecomastia
History:

Summary:

Exam:

Breast exam:
Inspection: bilateral breast enlargement
Palpatition: bilateral tender, symmetrical, discoid enlargement of glandular tissue beneath the nipple
and areola
male breast carcinoma – non-tender, eccentric hard mass

Diagnosis:

Questions:
1. Frequency: 50% to 70% of all boys during puberty and 30% to 65% of men have
palpable breast
2. Pathophysiology:
a. increased ratio of oestrogens to androgens
b. Tissue response of hormone is abnormal because of a defect at the receptor
level.
3. Neonatal gynecomastia: immediately after birth in boys influenced by maternal
oestrogens
4. Pubertal gnecomastia:
a. subsides in most within two years
5. unilateral disease:
a. higher incidence of left-sided disease
6. increased prevalence of breast cancer:
a. Klinefelter’s syndrome
b. exposed to high doses of radiation
c. occupational heat exposure
d. treatment with oestrogenic hormones, for example in prostatic cancer
7. mimics:
a. cystosarcoma phylloides
b. Hodgkin’s disease
c. Leukaemic or metastatic infiltration
d. soft tissue sarcoma
e. neurofibroma,
f. local injection of heroin

8. FNAC -
a. cohesive clusters of bland epithelial cells of ductal origin
b. superimposed myoepithelial cell
c. True terminal acini, as seen in the adult female breast, are rarely seen in men

9. three mammographic patterns of gynaecomastia

a. early nodular or florid phase

116
 b. latter dendritic pattern or fibrous phase
c. glandular pattern, commonly seen in patients on exogenous hormones

10. Breast ultrasonography

a. high-frequency transducers

11. Treatment: late stages, when the breast tissue consists mostly of dense fibrotic
stroma, medical therapy may be ineffective
a. idiopathic gynaecomastia-
i. tamoxifen
ii. danazol

12. semen analysis

13. Differential diagnosis:

a. misuse anabolic steroids to increase muscle mass: Skeletal muscle
hypertrophy and the triad of acne, gynaecomastia, and striae
b. Klinefelter’s syndrome
c. testicular tumours:
i. 5% and 10% - gynaecomastia
ii. Benign Leydig tumours often produce high concentrations of
oestrogens as opposed to androgens, and although they are rare up to
30% are associated with gynaecomastia
iii. human chorionic gonadotrophin
1. stimulates the testicles to produce both testosterone and
oestrogen
2. poor prognosis
3. ectopic production of hCG by other tumours such as
bronchial, gastric, or pancreatic carcinomas
d. prostrate cancer treatment:
i. exogenous oestrogens
ii. gonadotrophin-releasing hormone analogues
iii. finasteride,
e. Oestrogen-secreting adrenal tumours
f. hepatic tumours- increased aromatase activity in the tumour
g. liver disease
h. Hyperthyroidism
i. re-feeding after starvation
j. renal failure caused by testicular suppression
k. chronic lung diseases
l. HIV infection
m. Hyperprolactinemia: indirect role in gynecomastia by causing central
hypogonadism
n. Kennedy’s syndrome (X-linked spinal and bulbar muscular atrophy)
o. POEMS syndrome (P-polyneuropathy, O-organomegaly, E-endocrinopathy,
M-M protein, S-skin changes)
p. Drugs:

117
 i. Cimetidine
ii. Digitalis

iv. Omeprazole

118
 Approach to Addison’s case
Establish history
1. Hypocortisolism – postural dizziness, vomiting, diarrhea when stress like superimposed viral
illness
2. Raised ACTH – hyperpigmentation
Name Age sex occupation Resident of
P/C- Weakness, fatigue - years
Hyperpigmentation - years
History of present illness
a) Weakness, fatigue
b) hyperpigmentation
Negative history:
1. Koch’s contact
2. Cough, night sweats, fever
3. Exposure to bird dropping
4. Visited caves recently
5. Type 1 Diabetes Mellitus, hypothyroidism, premature ovarian failure, anemia, vitiligo
6. Tetany – hypocalcemia: in young individuals
7. Hypogonadism
8. Inability to produce tears
9. Motor complaints
PAST:
1. Addisonian crisis
Rx –
1. Exogenous steroids
2. Ketoconazole, etomamide
Personal history;
Addictions
Unprotected intercourse
Diet
Family history:
Summary

EXAMINATION
Hyperpigmentation: Palmar creases/ scars/ kemcha, arela
Vitiligo
Anthropometry: Wt Ht BMI WC
Vitals BP-Postural fall in BP
Cardinal signs
Special general examn
Hypothyroid features – Bradycardia, delayed relaxation of ankle jerks
Skin –
Hands – sweating, loss of thenar eminence
m.m., oral cavity, teeth –
Eyes
Spine, Joints –
Thyroid –

119
Testes
Body hair
BP
CVS –S1S2 Normal
RS
P/A- Hepatomegaly, speenomegaly
CNS –
Fundus
Other cranial nerve Palsies
Motor system – Bulk, tone, power of limbs
Carpal tunnel syndrome
Peripheral neuropathy
Peripheral nerves
DIAGNOSIS
Plan
Specific inv- Lancet 2014

Question:
1. DD of hyperpigmentation:
1. Addisons disease
2. Vit b12 deficiency
3. Nelson’s syndrome
4. Hemochromatosis
2. Incidence of 120etaphy’s disease: 6/million per year(Norway) lovas Clin.
Endo2002

120
 Approach to DSD

Case scenarios:
1. Newborn with enlarged phallus and no gonads
2. Newborn with enlarged phallus, unfused folds and palpable gonads
3. Female with primary amenorrhea
4. Female with virilization at puberty
5. Male with delayed puberty

History:
Ambiguous genitalia since birth

HOPI
1. Genital appearance at birth
2. Any palpable gonads at birth
3. Sex assigned at birth or post birth
4. For CAH – salt wasting , salt craving, lethargy, diarrhea, vomiting
5. For CAH-hyperpigmentation of genitals, nipples, palm, soles, oral mucosa

Family history:
1. Consagunity
2. Siblings or relatives with abnormal genitalia, corrective surgery of genitalia, still birth,
multiple miscarriages, infertility, hernia, delayed puberty, unexplained death, need for
steroidal replacement

Birth history:
Ante-natal period
1. History of drug exposure (progestins)
2. Assisted reproduction
3. Maternal virilization
Peri-natal period
1. Salt-wasting crisis

On examination

General appearance:
2. Hyperpigmentation

Anthropometry
3. Failure to thrive

Vitals
4. Hypertension
5. Hypotension

Genitalia examination:

121
1. Prader staging
1. Labio-scrotal fold- not fused/ partially fused/fused
2. Urethral opening- 2 perineal opening/ scrotal hypospadiasis/penio-scrotal
hypospadiasis/penile hypospadiasis
2. Phallus length/clitoromegaly
3. Any cordee
4. Any palpable gonads
5. Pigmentation of scrotal skin
6. Any adhesion
7. Anal opening

Diagnosis (Scenarios)
1. Ambiguity with enlarged phallus and no palpable gonads
1. 46 XX DSDincreased Androgen
1. Fetal Adrenal(CAH/Placental Aromatase)
2. Fetal Gonad(testis/ovotestis)
3. Transpacental(Medicine/tumor)
2. 46 XY DSD with undescended testis
1. Defective androgen synthesis
2. Abnormal gonad development
3. 46XY: Hypo Hypogonadal
2. Ambiguity with enlarged phallus, unfused folds and palpable gonads-46XY DSD
1. Testicular dysgenesis
2. Testosterone Biosynthesis defect
3. Testosterone action defect
3. Female phenotype with primary 122etaphysic, lower third vagina, no palpable gonads, no
other phenotypic features and a possible positive family history suggest the following
differential diagnosis in order of likelihood:
1. Complete androgen insensitivity
2. 46,XY gonadal dysgenesis (in this case there would be a lack of the upper
two thirds of the vagina, implying AMH secretion,and thus one would not
expect Müllerian duct structures to be present), if AMH absent: Mullerian
structure
3. Defect in testosterone/DHT biosynthesis (usually autosomal recessive, so
unlikely in this familial context)
4. Rarer causes of absent virilization in a 46,XY individual such as LH receptor
gene mutations.
5. XX Gonadal dysgenesis
6. 46X Gonadal dysgenesis
4. Female with virilization at puberty
Common causes
1. 17 βHSD3 def
2. 5α Reductase 2 def
Atypical
1. PAIS
2. Partial Gonadal dysgenesis /ovotestis DSD
3. CAH(46XX)
4. Androgen secreting tumor

122
1. Male with delayed puberty
1. 46XX DSD (male) SRT( +) !SRT(-)
2. Klinefelter Syndrome
3. Hypo Hypogonadism
4. Hyper Hypogonadism

Investigations;
1. First Tier:
Glucose/17 (OH)P/S. electrolytes
2. Second Tier:
1. Testosterone/Androstenidione/PRA/ Urine steroid profile
2. If not XX: AMH/HCG stimulation test
1. Hormonal:
1. Basal gonadotropins/testosterone
2. hCG stimulation test measuring testosterone and DHT : HCG 1000-1500 x 3 days
and on day 4 T/DHT/ Androgen
3. 17 (OH)P after 36 hrs
For diagnosis of CAH after infancy (jcem 2010)

2. Imaging:
— Genitogram.
— Ultrasound.
— CT or MRI.
3. Laparoscopic study looking for gonads and biopsy.

4. Furthet tests— These will depend to some extent upon the results of the first round of tests.

1. If there is lack of the upper two thirds of the vagina it might be quite difficult to
separate 46,XY gonadal dysgenesis from CAIS/testosterone biosynthetic defect
2. If a defect in testosterone synthesis or CAIS is likely (no Müllerian duct structures
and poor testosterone response to hCG), I would recommend a urinary steroid profile
to rule out 3 –HSD deficiency, 17 –HSD deficiency, etc.

123
 3. If gonadal dysgenesis is likely (with or without Müllerian duct structures and poor
testosterone response to hCG), I would recommend an inguinal laparotomy and
gonadal biopsy

Management:
1. For growing CAH patients: (jcem 2010)

2. Emergency measures for CAH

1. Correction of fluid & electrolyte disturbances
2. Correct hypoglycemia
3. Glucocorticoids: hydrocortisone 100mg/m2/day, divided in 3 to 4 doses

3. Monitoring CAH
1. Growth: maintain at centile of MPH
2. Plasma androstenedione: maintain at 20 to 50 ng/dl
3. 17 OHP maintain at 500 to 1000 ng/dl (15-30nmol/l)
4. Serum electrolytes, BP, PRA
4. CAH: long term Outcome Issues to be addressed
1. Final height
2. Obesity
3. Fertility
4. Sexual functions
5. Need of bilateral adrenalectomy
6. Prenatal treatment
7. ? Patients right for gender preference
5. Newer Concept of Medical Management
1. Anti androgens
2. Aromatase inhibitors
3. Adrenal androgen production blockade
4. LHRH analogue and GH
5. Delayed release formulations of glucocorticoids
6. CRH antagonists
7. Gene therapy

124
Questions:

1. Approach to DS

125
2. Approach to masculinized genetalia

126
3. Hormone profile in 46 XY DSD
diagnosis
Hormones
Normal cortisol CAIS/PAIS
Increased testo(HCG) 5α reductase deficiency
Increased precursor(HCG)
Normal cortisol 17 β HSD deficiency
Decreased testo(HCG) 17,20 lyase deficiency
Increased precursor(HCG)
Decreased cortisol 17 α hydroxylase deficiency
Decreased testo(HCG) 3 βHSD2 deficiency
Increased precursor(HCG) POR deficiency
Decreased cortisol StAR deficiency
Decreased testo(HCG) SCC deficiency
Decreased precursor(HCG) DHCR 7 deficiency- (smith lemli opitz)
4. Increased risk of gonadal Tumor in XY DSD: Gondoblastoma/ Dysgenesis
5. Normal Carrying angle
6. Mixed gonadal dysgenesis: most common  45X/46XY
7. Most common community:
1. Ovotesticular DSD: Black(S. Africa)
2. Lipoid CAH: Japan/Palesyine
3. CYP17 def: Brazil
8. Ovotesticular DSD: Most common:46XX
9. Gender Reversal at puberty:
1. 17βHSD def
2. 5αReductase def
10. Maternal Virilization:
1. Placental aromatase def
2. familial glucocorticoid resistance
11. Diagnostic Ratios:
1. 5αReductase(nmol/L): T:DHT> 30
2. 17βHSD3 (nmol/L): A:T>20
12. Aromatic def: increased androgen during perinatal period, followed by sex hormone def
13. Syndromes:
1. SLO(decreased DHCR7): decreased cholesterol
2. Denys Drash
3. Fraiser
4. WAGR
5. Robinow
6. Beckwith wiedimann
14. Ovotesticular DSD:
1. u/L ovotestis(50%)
2. b/L ovotestis(30%)
3. U/L ovary with u/L testis (20%)
15. Conditions causing male-hypogonadal and female- virilization
1. 3β HSD def: males decreased adrogens
Females –peripheral conversion to active androgens
2. POR: 21OH lyase + P450c17

127
16. DSD summary

128
129
17. Gonadal development

18. Presentations

130
19. Classification

131
20. Gonadectomy age

132
 Approach to micropenis

HISTORY
Parents noted short phallus
Passes urine through tip of penis
Obesity / weight gain/penile surgery
Marked virilization at puberty: 5αR2def/17β HSD def
F/S/O decreased GH/ACTH: decreased BS/ NNJ / Midline defect
F/S/O CAH: increased pigmentation/ salt wasting

C/Exam:
1. SPL
2. Corpora Cavernosum: Normal / hypoplastic
3. Testis: Vol/ anaorchia/cryptorchidism
4. Scrotum: normal/hypoplastic
5. Signs of delayed puberty
6. Location of meatus
7. Anosmia

Diagnosis:
Micropenis due to DD

Investigation:
1. Testo/LH/FSH(testosterone(Post HCG))
2. If LH reduced or inappropriately normal: IGF-1/ IGF BP3/ GHST/ ACTH/ cortisol/FT4/MRI
pituitary
3. If LH/ FSH increased : Karyotype/gonadal Bx/ DHT
4. Functional testis- AMH/ inhibin B

Management:
1. Testosterone(25mg every 3 wks for 3 months)
2. If GHD  GH
3. If no response to hormonal Rx- surgery
4. AI: DHT gel

Questions:
1. Definition: SPL < 2.55D mean for age/ stage of sexual development
2. SPL
Age -2.55 D
Term 2.5
5 yrs 3.5
11 yrs 4
Adult 9.5
3. Microphallus= Micropenis+ hypospadiasis

133
4. DD:
1. Hypogonadotropic hypogonadism
2. Hypergonadotropic hypogonadism
3. LH receptor defect
4. Androgen Action defect
5. GH/IGF-1 deficiency
5. Syndrome:
1. Klienfelter
2. Prader-willi
3. LMBB
4. Noonan
5. Rainbow(ROR)
6. Kallman
7. CHARGE
8. Pallister Hall
9. Reed(hypohypo)

134
 Approach to cryptorchidism
History:
1. Absence of testis
2. Micropenis/hypospadiasis
3. P/H of surgery
4. At birth: increased risk—preterm/ low B.weight/eclampsia/ Twins/NNJ/ Maternal Diabetes/
smoking- in parents
5. Family history
6. Salt wasting crisis

On Examination:
Testis: normal/ectopic/retractile/not palpable(frog leg position)
Scrotum:
Hypospadiasis:
Midline defect
Hyperpigmentation
Testicular sensation

Diagnosis
1. Cryptorchidism
2. If bilateral in newborn: SWCAH

Investigations:
1. Newborn: 17 (OH)P/ Electrolyte/Karyotype
2. Anterior pituitary hormones
3. Testo/DHT/LH/FSH
4. Imaging : 44% localize
5. Laproscopy

Management:
1. Medical
1. HCG: 250-500IU twice a week for 5 wks(15-20% I)
2. GnRH: Buserelin: 1-1.2mg Intranasal daily for 4 wks
3. Surgery: By 6-12 months of life
2. Surgery: By 6-12 months of life (95%sucess)

Question:
1. Testicular Descent
1. Abdominal Phase: INSL3- LG R8/RXFP2
2. Inguinal Phase: CGRP(G.F. Nerve)
3. Frequency
1. 4% of all Boys at birth
2. 70% unilateral
3. R:L=2:1
4. 0.8% at 6 months of age

135
4. DD
1. Hypo Hypogonadism
2. Hyper Hypogonadism
3. Androgen action defect
4. GH deficiency
5. Vanishing testis
5. Malignancy
1. Increased 4-10times
2. No surgery- seminoma
3. Post surgery-embryonal Ca
6. Earliest sign of tumor: loss of testicular sensation
7. Differential diagnosis
1. Undescended testis
2. Ectopic testis
3. Retractile testis

136
 Approach to hyperparathyroidism case
Complaints:
Multiple fractures
Bone pain
Renal stone
Irritability
Polyuria
Jaw tumor

Questions:
Causes of rugger jersey spine

1. Mx of hyperphospatemeia

2. PTH assay
1. 1 st gen

2. 2 nd gen

3. 3 gen

4. Turbo –

3. CKD stages

4. What is normocalcemic hyperparathyroidism?

1. elevated ionized calcium
2. vitamin D deficiency

5. What are the indications for parathyroidectomy in end-stage renal disease?

Indications for parathyroidectomy are:
1. Severe hypercalcemia
2. Progressive and debilitating hyperparathyroid bone disease
3. Pruritus that does not respond to dialysis
4. Progressive extraskeletal calcification or calciphylaxis that is usually associated with
hyperphosphatemia.
5. Otherwise unexplained symptomatic myopathy.
6. Renal transplant recipients with persistent HPT associated with hypercalcemia and
renal insufficiency.

6. What is band keratopathy?

1. classic but unusual sign of HPT
2. irregular region of calcium phosphate deposition at the medial and lateral limbic
margins of the outer edges of the corneas
3. result of diffusion of carbon dioxide from air-exposed areas of the cornea, leaving an
alkaline environment that favors precipitation of calcium phosphate crystals
4. occurs only with a high calcium phosphate product

137
 5. slit-lamp examination
6. differs from arcus senilis: rim of clear cornea that with time completely encircles the
cornea

Approach to hypogonadism

More specific symptoms and signs

1. Incomplete or delayed sexual development, eunuchoidism
2. Reduced sexual desire (libido) and activity
3. Decreased spontaneous erections
4. Breast discomfort, gynecomastia
5. Loss of body (axillary and pubic) hair, reduced shaving
6. Very small (especially less than 5 ml) or shrinking testes
7. Inability to father children, low or zero sperm count
8. Height loss, low trauma fracture, low bone mineral density
9. Hot flushes, sweats
Other less specific symptoms and signs
1. Decreased energy, motivation, initiative, and self-confidence
2. Feeling sad or blue, depressed mood, dysthymia
3. Poor concentration and memory
4. Sleep disturbance, increased sleepiness
5. Mild anemia (normochromic, normocytic, in the female range)
6. Reduced muscle bulk and strength
7. Increased body fat, body mass index
8. Diminished physical or work performance

History:
Chief complaints:
1. Delayed puberty
HOPI
Past history
1. Learning difficulty
2. Seizures
3. Height progress
Birth History
Family history
On Enq- hypoosmia

Exam
Gen appearnance
Tall; long arms and legs, poor muscular developmet

Anthropometry
Ht:
AS
US:

138
Wt:
AS>Ht
LS
BMI
BSA
US/LS:<0.9

Gen exam
P I Cy Cl OD skin
Gynaecomastia
Cleft lip/palate
Pes cavus

L. exam:
P1
Tv:R/L
SPL

Syst exam: RS/CVS/P.abdomen/CNS

HMF: Learning disability
Cr. Nerves : anosmia/ nystagmus/s.n deafness/ color blind
Motor: spastic paraplegic/ synkinesia
Sensation:
Reflexes:
Cerebellar: ataxia

Diagnosis:
Hypogonadism
D/D:
1. Hypogonadotropic hypogonadism
2. Hypergonadotropic hypogonadism

Investigation
First Tier
1. Testosterone
2. LH

Second Tier
MRI: if LH low/inappropriately normal

Management
1. Fertility not desired:
Testosterone(Cyptonate/enanthate)
1. 75mg i.m. monthly - 200mg q 2 weeks
2. Gel 2.5 mg daily  full replacement
3. Fertility desired
1. HCG
1. 1000-1500 IU(sc)q twice wkly

139
 2. Increased aromatase – gynaecomastia
2. After 6 months FSH may be added
1. 100-150 units (sc) 3 times/ week
2. Pregnancy rate upto 90% till 1 ½ yrs
4. Pulsate GnRH: increased testis size/ earlier sperm/ similarly sperm count

140
Questions:
1. Alternative names for male hypogonadism
1. Androgen deficiency syndrome
2. Androgen deficiency in the ageing male (ADAM)
3. Andropause
4. Late-onset hypogonadism
5. Male menopause
6. Partial androgen decline in the ageing male (PADAM)
7. Testosterone deficiency syndrome
2. Physiological effects of testosterone in male adults
1. Maintains reproductive tissues
2. Stimulates spermatogenesis
3. Stimulates and maintains sexual function
4. Increases body weight and nitrogen retention
5. Increases lean body mass
6. Maintains bone mass
7. Promotes sebum production, and axillary and body hair growth
8. Stimulates erythropoiesis

3. Normal semen analysis

4. clinical features of klinefelter(1:700) 1942

1. small testis(100%)
2. gynaecomastia(60%)
3. Learning problems
4. Behavioral Problems
5. G.C.T. (50 times more common)
6. Cryptoorchidism
7. Microphallus
8. Hypospadiasis
9. Tall stature
10. Delayed puberty
11. Thyroid dysfunction
12. T1DM

141
 13. osteoporosis
5. Cause of gynaecomastia in klienfelter:
1. Decreased testosterone increased LH  E2 increased E2/testo  gynaecomastia
6. Clinical features of kallman’s syndrome
1. Hypo. Hypo.
2. Anosmia
3. Nystagmus
4. Color blind
5. S.N. deafness
6. Seizures
7. bimanual synkinesis
8. Cerbellar ataxia
9. Spastic paraplegia
10. Learning difficulty
11. Cleft lip/palate
12. Renal ageneisis/ horseshoe kidney
13. Pes cavus
7. What assessment for congenital hypogonadotropic hypogonadism (CHH) should be
done?
1. sense of smell
1. quantitative or semiquantitative method is olfactometry
2. magnetic resonance imaging
2. Genes of kallman/ IHH
hypoosmic CHH normosmic CHH
1. KAL1 1. TAC3, TACR3
2. SEMA 2. GnRHr
3. NEL 3. Kiss, GPR54
4. FGF8, FGFR1 4. SOX
5. PROKR2, PROK2 5. DAX
6. CHD7
7. WT
8. HESX

6. Prader Willi Syndrome

1. Neonatal hypotonia
2. Obesity
3. Short stature
4. Small hands/feet
5. Mental retardation
6. Hypogonadotropic/hypogonadism
7. Lauren Moon Beidel syndrome
1. Pig. Retinal dyst
2. Obesity
3. Polydactly
4. Mental retardation
5. Hypogonadism
6. Renal abdomen
7. Spastic paraplegia

142
8. Mobius(congenital oculofacial paralysis)
1. Cranial nerve palsy
2. Seizures
3. Gait disturbances
4. Mental retardation
5. Hypogonadism
6. Limb anomaly(Poland syndrome)
9. Lowe’s syndrome
1. Cong cataract
2. Hypotonia
3. Mental retardation
4. RTA
5. Hypogonadism
10. Noonan’s syndrome
1. 1 in 200 birth
2. PTPN III mutation
3. Cryptoorchidism with primary testicular failure
11. LEOPARD
1. L-Lentigines
2. E-ECG abnormality
3. O-Ocular Hypertelorism
4. P-Pulmonary stenosis
5. abnormality genetilia
6. R- Retardation growth
7. D- deafness
12. Carpenter’s
1. Obesity
2. Hypoogonadism
3. Acrocephaly
4. Craniosynostosis
5. Agenesis of hands/feet
13. Pan hypopituitarism involvement gn
1. Prop-1
14. Galactorrhea in men with prolactinoma(A Colao JCEM 2004)
1. Only 10 to 20%
2. E2 is too low to cause breast development
15. Hemochromatosis:
1. Hypogonadotrophic Hypogonadism occurs early
2. Testicular failure uncommon
16. Thalasemia and hypogonadism
1. Hypogonadotrophic Hypogonadism > Primary Testicular failure

143
144
 Approach to precocious puberty
Definition
Onset of puberty below 2 SD from mean for sex and race, for Asians females below 8yrs and males
below 9yrs
Presenting complaints
Girls
Breast development
Enlargement of Labia minora
Menarche
Pubic hair
Boys Central precocious Puberty (CPP)
Enlargement of testes
Penile growth
Pubic hair
Boys – PPP
- No testicular enlargement
General
Growth spurt apparent at onset of puberty
Enquire regarding –
1. Age of onset of sec sexual characters
2. Rate of progression of puberty
3. Sequence of evolution of secondary sexual characters
4. Any features of contrasexual secondary characters
5. Growth spurt if any
6. For adrenarche: axillary, oily skin, acne

For Etiology
1. For CNS disease-headache, vomiting, visual fields defects, seizures, gelatic sezures,
behavioral changes, head trauma, intracranial infection radiation or surgery
2. Perinatal trauma
3. Exposure to gonadal steroids
4. Features of hypothyroidism
5. For MAS: bone pain, fractures, skin lesion
6. Hyperpigmentation- CAH and glucocorticoid resistance
7. For adrenal tumor- cushingoid features
8. For boys – asymmetrical, testicular enlargement
9. For girls- mass per abdomen, spotty bleeding,

Family History;

Examination:
1. General appearance-
1. Features of hypothyroidism, Cushing syndrome
2. Hyperpigmentation
2. Vitals
3. Anthropometry

145
4. Tanners staging

5. Testicular assessment
6. SPL
7. Changes in vaginal mucosa
8. Features of contrasexual precocity
1. Clitoromegaly
2. gynacomastia
9. Dysmorphism
1. Russel silver syndrome
2. Prader willi syndrome
10. Skin –
1. Café au lait spots- MAS,
2. Acne
3. Body odor
4. Hirsuitism- modified FGS
5. Acanthosis
11. Thyroid examination
12. Systemic examination
1. Chest
2. CVS
3. Abdomen – mass
4. CNS-
1. Features of rised ICT
2. Field cuts
3. Fundus

146
Summary
3yr old girl with
Features of precocious puberty
In the form of ---
With absence of ---
Diagnosis:
A case of precocious puberty most likely
1. Central
2. Peripheral
With etiology being---
Investigations:
1. NEJM

2. Basal FSH, LH
1. Basal LH > 1.06 mIU/ml
1. Boys Sensitivity : 70%, specificity 100%
2. Girls Sensitivity : 60%, specificity 100%
3. LHRH Stimulation test: Naferlin/ Leuprolide
1. Pubertal response : Peak LH response > Peak FSH
2. Pre –pubertal: normal LH, mild increased FSH
3. LH(mean pubertal)
1. Boys :9.6 mIU/ml
2. Girls : 6.9 mIU/ml
4. Imaging:
1. Skeletal Xrays
1. Bone age assessment
2. Fibrous dysplasia
5. MRI: Pituitary 6.USG: Pelvis

147
Questions:
1. Approach to breast development before 7 yrs

148
2. Pubic hair before 7 years of age in a girl

149
3. Precocity in male:

4. Approach to differential diagnosis in male

1. Pubic hair only

D/D Investigations
1. Precocious adrenarche 1. Bone age
2. LOCAH 1. PA- less than 2 SD advance
3. Exogeneous testosterone in bone age
4. Adrenal tumor 2. 17 OHP
5. Glucocorticoid resistance 3. USG abdomen
6. Insulin resistance 4. CECT abdomen

1. Pubic hair with increased phallus with symmetrical increase in both testicular volume
D/D Investigations
1. Central Precocious puberty 1. Bone age
2. Leydig tumor 2. Testosterone
3. Testotoxicosis 3. LH-basal and stimulated
4. 4.

150
 1. Pubic hair with increased phallus with asymmtercial increase in testicular volume
D/D Investigations
1. CAH with testicular adrenal rest 1. 17 OHP
tumor 2. USG scrotum
2. Testicular tumor 3.
3.

1. Pubic hair with increased phallus with normal/reduced testicular volume

D/D Investigations
1. Virilizing CAH 1. 17 OHP
2. Adrenal tumor 2. Serum cortisol
3. Glucocorticoid resistance 3. ACTH
4. DHEAS
5. Testosterone

6. Familial Testotoxicosis: Familial male precocious puberty

1. Autosomal dominant
2. Gain of function mutation of LHR
3. Testosterone in pubertal range
4. LH- low both basal and stimulated
5. Female- asymptomatic
6. Testis: small as compared to degree of virilization
7. Treatment:
1. Ketoconazole
2. Spironolactone + testolactone(best)
3. Bicalutumin+ anastrazole

7. Females: Approach to diagnosis

1. Thelarche only
D/D Investigations
1. Isolated premature thealrche 1. Bone age
2. Exogenous estrogen 2. USG pelvis
3. Central precocious puberty 3. TSH
4. MAS 4. LH- basal and stimulated
5. Primary hypothyroidism 5. Skull x-ray –if MAS suspected
6. Ovarian cyst

151
1. Thelarche with pubic hair
D/D Investigations
1. Central precocious puberty 1. Bone age
2. Ovarian follicular cyst 2. USG pelvis
3. Ovarian tumor 3. LH- basal and stimulated
4. Insulin resistance 4. Blood sugar-F/PP

5. Pubic hair only

D/D Investigations
1. Isolated precocious adrenarche 1. Bone age
2. NCCAH 2. 17 OHP
3. Glucocorticoid resistance 3. Testosterone
4. Insulin resistance 4. DHEAS
5. ACTH
6. Blood sugar-F/PP

7. Pubic hair with virilization

D/D Investigations
1. Virilizing adrenal tumor 1. 17 OHP
2. Virilizing ovarian tumor 2. DHEAS
3. CAH- salting wasting 3. Testosterone
4. CAH-3beta HSD 4. ACTH
5. Glucocoticoid resitance 5. Blood Sugar fasting
6. Insulin resistance
7. Aromatase deficiency

1. Premature adrenarche
1. Boys less than 9 yrs
2. Girls less than 8 yrs, asian girls < 7yrs
3. Male:female ratio 1:10
4. Isolated premature adrenarche-
1. increase of 17αhydroxylase
2. Decrease in SULT 2 A1- it will cause increase in DHEA level
5. DD
1. NCCAH
2. GC resistance
3. Insulin resistance(upto 45% may develop PCOS)
4. Cushing syndrome
5. Increase HSD11B1 activity?
6. Virilization tumor: adrenal/ gonadal

2. Normal sequence of adrenarche

I II III
1. Normal zona 1. Detectable androgen 1. Features of pubarche

152
 reticularis maturation synthesis 2. 10-12yrs
2. 6-8yrs 2. 8-10yrs
3. DHEAS < 50mcg/dl 3. DHEAS > 50mcg/dl

1. Treatment objectives:
1. Detect/treat underlying lesion
2. Arrest of secondary sexual characters until appropriate age
3. Attainment of normal height
4. Psychological aspect/reduction of risk of sexual abuse
5. Preserve fertility
6. ? Risk of Ca Breast

1. Differentiating progressive precocious puberty

153
1. Indications for treatment:
1. Rapid advance in
1. Secondary sexual characters
2. Growth
3. Bone age
2. Sustained elevation in gonadal steroids
T > 0.75 ng/ml
E2 > 10 pg/ml
3. Menarche in girls < 9 years
4. Psychological factors

2. Medroxy Progesterone Acetate: 5-20 mg twice/day, oral, gluco-corticoid action : H-P-A

suppression
3. Cyproterone acetate: 100 mg/m2/day Progestational, antigonadotropic action and Suppresses
ACTH – Cortisol
4. LHRH Analogues
1. Selective, highly specific : medical gonadectomy by down regulating GnRH receptor
2. Suppression of LH, FSH   gonadal steroids
3. Blocks release of LH/FSH in 1–2 wks of treatment
4. Gonadal steroids  in 2- 6 weeks
5. Regression of secondary sexual character in 6-12 months
6. Bone age advancement controlled
7. No effect on BMD or BMI (long term)
8. Height gain 3-10cm average 5cm
9. Goal-target height, age of puberty reached
10. Takes 1 yr to resume spontaneous axis: Pulsatile LH(4 months), menarche (18
months)
11. No benefit of GnRH agonist with aromatase inhibitor :

154
5. Management of peripheral precocious puberty

1. Ovarian cyst- MPA

2. MAS- MPA, aromatase inhibitor
3. Male precocious puberty- MPA with ketoconazole, flutamide
4. If secondary central precocious puberty- GnRH agonist
6. Monitoring:
1. Sec sexual characters : takes 6 months
2. Growth rate : reduces below CA
3. BA : advance slows down
4. USG Pelvis :  in size of uterus/ovaries
5. FSH, LH : 3rd generation assay
6. Target Gonadal Steroid : T < 0.2 mg/ml, E2 < 5pg/ml
7. Impact on cessation of therapy:
8. Resumption of puberty in 6 months to 2 years
9. Ovulation documented in 90%, 2 yrs after menarche

7. Adult height depends on:

1. Age of onset of precocity
2. Advancement of BA
3. Rate of progression of puberty
4. Age at onset of treatment

8. Premature Thelarche
1. MC: Infantry to 3 yrs
2. Upto 15% may progress to central precocious puberty
3. Management: careful follow-up; growth velocity; X-ray: bone age
4. DD:
1. Fibroadenoma
2. Abcess
3. Haemmorhagic cyst
4. Metastasis

9. Pubic hair of infantry

1. Usually atypical location: scrotun/ mons pubis
2. Resolve spontaneously

155
10. C.P.P.
1. Boy< Girl
2. Boys: Idiopathic 10-50%
3. Girls: Idiopathic 90%
4. Familial: upto 25%
5. Etiology
1. Structural lesion ---cyst(pineal/suprasellar), Sep to optic dysplasia, neurofibromatosis
2. Insult- head trauma/hydrocephalus
3. Genetic-GPR54
6. Investigations:
1. GnRH stimulation test
2. MRI sella
3. USG pelvis

11. McCune Albright syndrome/Triad: (Arg201 cys/His), increased GSα, increased cAMP
1. Precocious Puberty(F>M): Gonads> Adrenals, parathyroid, pituitary, thyroid
2. Polycystic fibrous dysplasia
3. Café au lait spots ---irregular ―coast of maine‖
4. Others: Hepatomegaly; cardiac; sudden death
5. Increased FGF23(from fibrous cells)- hypophosphatemia
6. Treatment:
1. MPA- disappointing
2. Aromatase inhibin- testolactone: disappointing
3. Newer generation aromatase inhibitor
1. Anastrazole-poor
2. Lentrazole-good response
4. SERM: Tamoxifen- good response
5. Pure estrogen receptor antagonist- falsodex(under study)
12. Ovarian Tumor: M.C. cause of P.P.P.- 156etaphysi cell tumor
13. Testicular tumor: Leydig (3 % of all testicular tumor); Ravdy sertoli cell tumor
14. Germ cell tumor (non-gonadal)—
1. Sites: Liver, lung, mediastinum, pineal gland, basal ganglia, Hypothalamus, thalamus
2. Marker: A.F.P; β HCG; Pregnancy specific β1 glycoprotein
15. Hypothyroidism (Van Lvyk grumbach syndrome)
1. Girls: estrogenic manifestations
2. Boys: Macroorchidism without virilization
3. P.P. without delayed bone age

156
16. Etiology

1. Overview

157
158
 Approach to delayed puberty
Definition:
1. Failure of onset of sec sexual characters in girls : 13 years, Boys : 14 years
2. Primary amenorrhea : 16 years
3. Failure of progression of puberty in 4 years from its onset
14 years old male
1. Short Stature noticed for noticed for last 2 to 3 years
2. Lack of development of secondary sexual characters
3. Features of adrenarche- pubic hair(females), axillary hair both sexes
HOPI
4. For Kallman syndrome- anosmia, family history
5. Shorter than friends and peers- turner syndrome, MPHD
6. Recent decrease in growth velocity- acquired growth hormone deficiency
7. Parents are average in height
8. Onset secondary sexual characters, puberty in parents
9. Features of turner syndrome
10. Headache, visual field defects, polyuria-intracranial tumor
11. For prolactinoma- galactorrhea
12. Features of malabsorption- abdomen pain, diarrhea, steatorhhea
13. For RTA- polyuria, proximal muscle weakness bone deformity, bone fracture, renal stones
14. For hypothyroidism-constipation, cold intolerance, dry skin
15. Features of cushing syndrome
16. For autoimmunity- alopecia, vitiligo, adrenal insufficiency
17. For pro-convertase deficiency, hypo-pigmentation, red hair
18. Obesity-prsder-willi syndrome, LMBB, PHP1a
19. adrenal insuffieciency- proconvertase deficiency, DAX-1 mutation, autoimmunity
20. mental retardation/ Average in school performance
21. excessive physical activity
22. features of steroid synthesis defect- hypertension, adrenal insufficiency
23. history of intracranial surgery or radiation
24. exposure to drugs
25. for gonadal failure- cryptorchidiam, gynaecomastia, testicular torsion, surgery, radiation,
mumps in childhood
16 yr old female
1. Delayed breast development
2. Delayed onset of menses
3. Presence of axillary and pubic hair

HOPI
4. For Kallman syndrome- anosmia, family history
5. Shorter than friends and peers- turner syndrome, MPHD
6. Recent decrease in growth velocity- acquired growth hormone deficiency
7. Onset secondary sexual characters, puberty in parents
8. Parents are average in height
9. Features of turner syndrome
10. Headache, visual field defects, polyuria-intracranial tumor
11. For prolactinoma- galactorrhea
12. Features of malabsorption- abdomen pain, diarrhea, steatorhhea

159
13. For RTA- polyuria, proximal muscle weakness bone deformity, bone fracture, renal stones
14. For hypothyroidism-constipation, cold intolerance, dry skin
15. Features of cushing syndrome
16. For autoimmunity- alopecia, vitiligo, adrenal insufficiency
17. For pro-convertase deficiency, hypo-pigmentation, red hair
18. Obesity-prsder-willi syndrome, LMBB, PHP1a
19. adrenal insuffieciency- proconvertase deficiency, DAX-1 mutation, autoimmunity
20. mental retardation/ Average in school performance
21. excessive physical activity
22. features of steroid synthesis defect- hypertension, adrenal insufficiency
23. history of intracranial surgery or radiation
24. exposure to drugs
Examination:
General appearance
Anthropomentry
25. Height : 143 cm, just below the 5th percentile, heightage
26. MPH : 25th percentile
27. US/LS : 1 (if<0.9 eunuchoid)
28. Arm span (if AS> Ht+5: eunuchoid)
29. Weight : 32 kg weightage
Vitals

General examination
1. Features of turner syndrome
2. Fetures of Cushing syndrome
3. Features of Prader willi syndrome
4. Features of LMBB
5. Features of PHP1a
6. Gynacomastia,
7. galactorrhea,
Systemic examination
RS
CVS
CNS: Fundus and visual field
Abdomen
Summary:
1. 17 yr old female with
1. Delayed onset of puberty, menses with
2. Positive findings of
3. Absent features of
Diagnosis:
Delayed puberty with most probable eitiology being
DD
1. Hypogonadotropic, hypogonadism
1. Mutation of:KAL, FGFR1, GnRH, GPR54, FSHβ, FSHR, LHβ, LHR, Leptin,
LeptinR, PC1
2. MPHD, PROP-1, LHX-3, HESX1, Pit1
3. CDGP

160
 4. CNS lesion
5. Systemic illness
6. RTA
7. Cushing’s syndrome
8. Primary hypothyroidism
9. Hyperprolactinemia
10. DAX1
2. Hypergonadotropic, hypogonadism
1. Gonadal failure – surgery, trauma, radiation, galactosemia, fragile-X, Previous
infection(mumps)
2. LH/FSH recptor deficiency
3. Aromatase deficiency(females)
4. Steroid synthase deficiency
5. Turners syndrome(female)
6. Klienfelters syndrome(male)
7. autoimmune
DD of primary amenorrhea
1. Normal breast development
1. Uterus present:
1. PCOS
2. Outflow obstruction
2. Uterus absent
1. 46XX: mullerian development
2. 46XY: A.I.S.
2. Delayed Breast development
1. FSH increased: gonadal dysgenesis: 46XX/45X/46XY
2. FSH(N/decreased) Hypo hypo

Questions:
1. Management objectives
1. Determine eitiology
2. Induce and maintain secondary sexual characters
3. Induce pubertal growth spurt
4. Avoid psycosocial, complexes
5. Ensure normal libido and potency
6. Attain fertility
7. Maintain bone health
2. Elevated gonadotropins
1. Gonadal failure – surgery, trauma, radiation, galactosemia, fragile-X, Previous
infection(mumps)
2. LH/FSH receptor deficiency
3. Aromatase deficiency(females)
4. Steroid synthase deficiency
5. Turners syndrome(female)
6. Klienfelters syndrome(male)
7. autoimmune

161
3. low or normal gonadotropin
normal growth Late onset growth Early onset growth
1. isolated retardation retardation
gonadotropin 1. CNS 1. CDGP
deficiency involvement 2. MPHD
2. athletes 2. Systemic disease 3. Syndromes
3. psychosocial 3. RTA
4. NCCAH 4. Other endocrine
causes

4. Indications for therapy

1. CDGP if child more than 12 yrs
2. Hypogonatropic hypogonadism
3. Child more than 11 yrs
5. CDGP management
Boys Girls
1. Testosterone 50mg i.m. 3 weekly 1. E2 5mcg OD for 6 months
for 6 months 2. 4-6months break
2. Then break for 4-6 months 3. If no spontaneous estrogen E2
3. If no spontaneous testosterone production then repeat
induction then repeat 1. If no spontaneous puberty in next
4. If no spontaneous puberty in next one yr
one yr 2. Then diagnose hypogonadotropic
5. Then diagnose hypogonadotropic hypogonadism
hypogonadism
Other agents: 3rd gen aromatase inhibitorletrozole (male)
3. Management of hypogonadotropic or hypergonadotropic gonadism
1. Once diagnosis is confirm
2. If CDGP regimen fails
Boys Girls
1. Testosterone 50mg i.m. 3 weekly 1. E2 5mcg OD
2. Increase every 6 months 2. Increase every 6 months
3. Till a dose of 250mg i.m. 3 weekly 3. Till a dose of 20mcg OD
4. Monitor mid-cycle and end-cycle 4. If breakthrough bleeding or
testosterone, tanner staging withdrawal bleeding after
reaching 15mcg OD
5. Start cyclical progesterone
D15-D25

6. Turner features:
g. Gonadal dysgenesis (95%)-
h. Short(100%)
i. Short, webbed neck
j. Fish mouth
k. Multiple nevi
l. Intestinal telangiectasia
m. Hypertelorism

162
 n. Epicanthus
o. Ptosis
p. Prominent low set posteriorly rotated ears
q. Recurrent otitis media
r. High arch palate
s. Micrognathia
t. Low hair line
u. Congenital lymphedema
v. Keloids
w. Shield chest
x. Hypoplastic nipples, wide spaced
y. Cubitus valgus
z. Short 4th metacarpal
aa. Turned out hypoplastic finger nail
bb. Celiac disease
cc. Coarctation of aorta
dd. Bicuspid aortic valve
ee. Horseshoe kidney
ff. Motor dysfunction
gg. Increased US/LS

7. Pituitary Transcription factors:

hh. Pit 1: GH(-), Prolactin(-), TSH (-), ACTH(+), Gn (+), Gn(-), ACTH(+)
ii. Prop 1
jj. LHX3: Gn(-)
kk. LHX4: Gn (+/-)
ll. HESX1: SOD(+) isolated GH  Panhypopitutarism
mm. SOX2: anopthalmia, Gn(-)
nn. DAX1: adrenal failure with Gn(-)
8. Bouncher- Necchaeusen syndrome:
9. Kalman syndrome:
oo. XL-KAL; AD: FGFR1, NELP
pp. Associates- cleft lip, hearing loss, color blindness, abnormal eye movements,
unilateral renal agenesis, synkinesis
10. CDGP:
qq. M.C: cause of delayed puberty
rr. FH: female: late menarche; male: significant gain in height late teens
ss. Boys=girls
tt. Spontaneous puberty:
i. Boys- by bone age of 13 yrs
ii. Girls- by bone age of 12 yrs

163
164
 Approach to Rickets
Ms , yr old female
Symptomatic since the age of 7-8 yrs
Presented with:
1. Wrist swelling / deformity
2. Bowing of the legs…. progressive outward deviation of……
HOPI:
1. Onset and progression of deformity
2. Enlargement of head
3. Chest deformity
4. Slowing of linear growth
5. Waddling gait (proximal myopathy)
6. Bony pains, fractures
7. Failure to thrive
8. Abdominal pain, loose motion, steatorrea- for celiac disease, IBD
9. Oliguria, weight loss, for CRF
10. Jaundice for liver failure
11. Drugs-anti-convulsants, antacids
12. Outdoor activity and sun exposure
Rarely:
1. grand mal seizures --- hypocalcemia related
2. carpal pedal spasms
3. delayed milestones
4. delayed tooth eruption
5. dental caries
6. cardiac failure ------ hypocalcemia related
7. hypotonia
8. polyuria, hyocalemic paralysis, deafness- for RTA
9. in infants-sun exposure and calcium intake in mother
For etiology:
1. No poor wound healing / night blindness / bleeding tendencies
2. No polyurias / graveluria / renal stones
3. No h/s/o inflammatory myopathy / arthritis
4. No anti convulsant intake

Diet history:
1. Calcium, calorie and protein intake
2. Milk intake < 20 ml per day (no egg / no meat diet )
3. Calcium intake < 200mg per day
4. Vit D supplementation in infancy
5. Foods rich in vit D, egg yolk, sea water fish, liver oil, mushrooms
6. Use of foods high in phytates

Personal history
1. Dark skin color
2. Sun exposure poor
3. loose stools on milk intake
4. No definite steatorrhea

165
Family history
1. Hypophosphatemic rickets
2. RTA
3. Skeletal dysplasia
4. OI
Social history
1. House type
2. Psychosocial issues
Birth history
1. Non consanguineous marriage
2. Vit D supplementation during pregnancy
3. Prematurity
4. birth weight 3 kgs
5. Normal perinatal period: No neonatal seizures
6. Prolonged excessive breast feeding, weaning
7. no failure to thrive
8. No delayed dentition

Development history
1. Normal development till ……… yrs
2. Menarche 12 yrs: has normal cycles (3/30 Regular)

Summary
10 year old girl presented with short stature and knock knees
With positive findings of ---
Exam:
General appearance- malnourished, irritable
Vitals
Pallor, icterus, cyanosis, clubbing
Wt: 9.8 kgs (5th centile); weightage
Ht:75 cm (<5th centile); heightage
MPH= 166 cm….. Short stature may be a feature in hypophosphataemic rickets
US:LS
1. Head:
1. Circumference
2. frontal bossing
3. Easy depression of soft parieto occipital region (craniotabes)
4. Soft persistant anterior fontanelles, posterior fontanelle
5. delayed tooth eruption
6. enamel hypoplasia
7. Head sweating
8. Cataract
9. Chevostek sign
10. alopecia

11. Thorax:

166
 1. rachitic rosary
2. Harrison’s sulcus
3. Pectus carinatum
4. kyphoscoliosis,

12. Abdomen
13. Dysmorphic features
14. Upper limbs:
1. Metaphyseal swelling
15. Lower limbs
1. Genu varus- ICD
2. Genu valgus- IMD
3. Genu recurvatum
4. Wind swept deformity of knees
5. Metaphyseal swelling
6. Bony tenderness +
1. No e/o hemangiomas /soft tissue masses/ sebaceous naevi/ fractures.
2. No e/o neuro cutaneous markers.
Systemic examination:

1. Chest – respiratory infection

2. CVS – heart failure
3. Abdomen- pot belly, visceromegaly, renal mass
4. Neurology:
1. hypotonia
2. Restlessness/irritability
3. significant Proximal myopathy
4. carpal pedal spasms
Summary
1. 10 year old girl presented with short stature and knock knees
2. With positive findings of ---

Diagnosis:
Rickets
1. calcepenic
2. phosphopenic
3. With most probable etiology being---
1. Nutritional
2. RTA
3. CKD
4. CLD
5. Skeletal dysplasia---(MD, SEMD, pseudochondroplasia, blounts disease, ED)
6. VDDR(if early onset)
7. Hypophosphatemic rickets

Investigations
4. Biochemical investigations:

167
 1. Initial
1. Calcium,
2. alkaline phosphatase – maybe normal in protein energy malnutrition, burnt-out disease, blount
disease, skeletal dysplasia
3. phosphate- nutritional deficiency is rare, if low suspect hypophophatemic rickets
4. Liver functions
5. Renal functions
6. Plasma 25 hydroxyvitamin D (25OHD)
1. Second tier
7. VBG- RTA
8. Serum parathyroid hormone (PTH)- if normal suspect hypophosphatemic rickets, if elevated
then VDRR
9. Plasma 1,25(OH)2D3
10. Urine calcium, phosphate, creatinine
11. Tubular reabsorption of phosphate (TRP)
12. Tubular maximum for phosphate reabsorption (TmPO4/GFR)

1. Radiological investigation
X- rays of wrist and knee
1. Xray wrist- rachitic changes: epiphyseal widening, 168etaphysical cupping, fraying, healing
line, fractures, fuzziness of provisional calcification zone; diffuse osteopenia
2. Secondary hyperparathyroidism: intracortical tunneling, bullet digits
3. Hypophophatemic rickets—thick cortex and increased density
4. RTA- coarsening
5. Skeletal dysplasias –metaphyseal abnormalities, with spine showing platyspondyly, cuboid
vertebrae
6. Bone age 4.5 yrs.
7. Xray knee- Fraying of lower femoral epiphyses s/o rickets. No e/o thick cortices or coarse
trabeculae.

Slit lamp examination- No e/o cataract/cystine crystals in cornea .

No e/o glycosuria.

168
Questions:
1. Clinical features as per different age groups.
1. During infancy, irritability, sweating, seizures,jitteriness, cardiomyopathy, delayed
milestones, delayed dentition, craniotabes, delayed closure of anterior fontanelle and
bossing of the skull can be seen
2. In the older child, waddling gait, Harrison sulcus, rachitic rosary, genu valgum, genu
varum (intercondylar distance more than 5cm) or windswept deformity are known to
occur.
3. In adolescence, seizures and bone pain are the major features one would encounter.

2. Classification of rickets:
Calcepinic Phosphopenic
Short stature - -/+
Onset 2nd year of life
Limb involvement Predominantly lower limbs
involved
Features of Vit D def myopathy, bone pain, tetany

Alkaline phosphatase High Marginally elevated

PTH High Normal – usually
High – mutations of Klotho
Vit D Low Normal
3. Healing phases:
1. 4 th week: ALP downward trend
2. 6 th week: line of healing.
4. Type1 VDDR
1. AR, 12q13
2. Presents in first 2 yrs like nutritional rickets
3. Clinical and radiological features like rickets
4. Low 1,25 OHD
5. Proximal weakness, delayed motor development, significant growth retardation
6. Treatment- calcitriol with calcium and phosphate

5. Type 2 VDDR
1. AR
2. Mutation: LBD(-) receptor negative
3. Mutation: DBD(-)receptor positive
4. Alopecia in severe cases
5. Hypocalcemia in severe cases
6. Presents in early infancy
7. Maybe lethal in perinatal period
8. Treatment high dose calcitriol with high dose calcium

6. Blounts disease/ tibia vara

1. Defective development of tibial growth plate
2. Progressive
3. no change with age or medical treatment

169
 4. common in young males, overweight children, Africans
5. treatment surgery

7. Discuss the histologic features of osteomalacia.

The two diagnostic histologic findings
1. widened osteoid seams
2. increased mineralization lag time: administering two short courses of oral tetracycline several
weeks apart, measuring the distance between the two fluorescent tetracycline bands
3. Depending on the cause of the osteomalacia, hyperparathyroid bone changes may also be seen
4. bone biopsy remains the gold standard
5. Vitamin D deficiency in healthy hospital staff of north India …… Osteoporos Int. 2004
1. With 25(OH) D level of 20 ng/ml as a cutoff, 80 % subjects were diagnosed to be
vitamin D deficient/insufficient
6. Vitamin D deficiency in pregnant women of north India….. Am J Clin Nutr. 2005
1. Mean maternal serum 25(OH)D was 14 ng/mL
2. Mean cord blood 25(OH)D was 8.4 ng/mL
3. PTH rose above the normal range when 25(OH)D was <22.5 ng/mL
4. 84 % women had 25(OH) D values below that cutoff
5. Adolescent girls 90% (< 20 ng/ml), pregnant females 75% (< 20 ng/ml)…. Clin
Endocrinol (Oxf) 2009
6. 60,000 U and two doses of 120,000 U vitamin D₃ had a beneficial effect on infant
anthropometry, the larger dose also improving Cord Blood ALP and maternal
25(OH)D…..Br J Nutr 2012
7. Calcium absorption

170
8. Calcium excretion

9. Hypophosphatasia

171
 10. Management:
1. Hypoposphatemic rickets
1. Joulies solution (30.4 mg) of inorganic phosphate/ml.
1. 136g dibasic sodium phosphate and 58.8 g phosphoric acid in 1 litre
of water
2. 3.66g disodium hydrogen phosphate and 1g sodium dihydrogen
phosphate dissolved in 60 ml water gives 1g elemental phosphorous
2. Nutritional rickets(stoss therapy) Ref
1. Cholecalciferol-1.5lac units in infancy, 3 lac units in childhood(over 6
weeks) followed by maintenance dose with adequate milk intake and sun
exposure
2. APEG: stoss therapy is not recommended for children less than 3 months of
age; for older children a more conservative approach of a single initial dose
of 50,000 to 150,000 IU is recommended
3. Calcium DRI(IOM)
EAR RDA ULI
0-6months 200 (AI) 1000
6-12 months 260(AI) 1500
1-3 yrs 500mg 700mg 2500
4-8yrs 800 1000 2500
9-18yrs 1100 1300 3000
20-50yrs 800 1000 2500
51-70yrs(M) 800 1000 2000
51-70(F) 1000 1200 2000
>70 1000 1200 2000
Pregnancy and 1100/800 1300/1000 3000/2500
lactation (<18/>18)

1. Vit D- AAP (wagner 2008)—all children 400 IU

2. Vit D- AAP, LWES(misra 2008)—all children 400 IU except upto 800 IU in premature, darkly
pigmented and who reside at higher latitudes (particularly above 40°)

3. Vit D(DRI)- IOM

EAR RDA ULI
0-6months 400 (AI) 1000
6-12 months 400(AI) 1500
1-3 yrs 400mg 600mg 2500
4-8yrs 400 600 4000
9->70yrs 400 600 (except 800 for 4000(ULI not known
above 70) for 14-18yrs)
Pregnancy and 1100/800 1300/1000 3000/2500
lactation (<18/>18)

4. Vit D(endocrine society 2011)

suggest For 25OHD >/= ULI treatment
30ng/ml
0-6months 400 1000 1000 2000

172
 6-12 months 400 1000 1500 2000
1-3 yrs 600 1000 2500 4000
4-8yrs 600 1000 3000 4000
9-18yrs 4000 4000
19-70yrs 600 1500-2000 4000 10000
>70 800 1500-2000 4000 10000
Pregnancy and 600 1500-2000 4000 10000
lactation

11. RTA

173
 APPROACH TO SHORT STATURE
Chief Complaints
1. Poor height gain
2. Poor weight gain

HOPI:
1. Onset- when did they notice,
2. Comparison with peer and classmate
3. Appetite/ gross diet
4. any documented growth velocity,

174
5. shortest in class
6. whether any younger siblings have overtaken him in height
7. delayed puberty

Secondary causes:
H/o hypothyroid symptoms
H/o bony pain, deformity, PMW for rickets also ask for sun exposure and milk intake
H/o headache, vomiting, visual complaints to suggest SOL (high ICT)
H/o polyuria, polydipsia, nocturia, renal stone for RTA
H/o Weight gain, abdominal striae, Proximal Muscle Weakness, easy bruising – Cushings syndrome
H/o Carpopedal spasm, perioral numbness – Pseudohypoparathyroidism (also in rickets during
adolescents)
H/o Significant head injury
H/o cranial SOL, surgery, irradiation
H/o CNS infections – TBM
Sun exposure/ physical activity
History suggestive of cortisol insufficiency, hypothyroidism, delayed puberty- MPHD
H/o delayed puberty – can occur in hypothyroidism, systemic illness, SOL (craniopharyngioma),
panhypopitutarism, celiac disease, most important CDGP in boys and TURNERS SYNDROME in
girls, rarely Zinc deficiency causing stunting and delayed puberty, noonans syndrome, PHP1a (Gn
resistance)
– all except Isolated GHD

rarely precocious puberty in CongenitalHypothyroidism, CAH

H/o parental relationship – psychosocial dwarfism – functional

H/o Scholastic performance – MR in RSS, Downs, Noonans,

Any bony deformity- skeletal dysplasia
In females history suggestive of turners syndrome, deafness, sinusitis
H/o chronic systemic disease – (SSRRCCHP)
CLD - jaundice,
CKD-pedal edema, dialysis, hypertension
IBD-chronic abdominal pain, diarreohea
Celiac disease – abdominal pain, steatorrhoea, diarrhea, anaemia
CHD-cyanotic spells, effort dyspnea
RS -Bronchial asthma, cystic fibrosis – ayurvedic drugs / steroids, nocturnal symptoms

BIRTH HISTORY:
Consanguinity –
1. GH gene mutation AR, AD, XR,
2. Achondroplasia – 10% AD (90%-sporodic)

Antenatal: fever, rash during pregnancy – TORCH infections, smoking, alcohol, PIH

Natal: FTND - Breech delivery?? forceps??( birth trauma)

Postnatal:

175
Birth wt – IUGR – substance abuse
whether catched up or not (15% don’t), RSS, chromosomal causes
Micropenis
undescended testes
prolonged jaundice – CH(indirect), GHD (cholestatic)
Edema of hand and feet - turners
seizures – hypoglycemia
feeding difficulties, failure to thrive, umbilical hernia, constipation- CH
Delayed milestones –
Motor – GHD, rickets, LMBS
Mental – CH, PHP, PWS

Family history – FSS- family history of short stature, CDGP- delayed shaving in father, delayed
menses in mother, delayed height gain in either parents, other affected siblings - achondroplasia, GHD

Personal history : psychosocial history

diet history –
1. Calcium intake per day
2. Calorie intake per day
3. Protien intake per day
4. Iron intake per day
5. Sun exposure

Summary
1. 16 yeqr old female
2. Physiological/ pathological: Short stature since 5 yrs
3. Delayed puberty
4. Features of hypothyroidism
5. No features of …..

GENERAL EXAMINATION:

Appearance
Malnutrition
Vitamin deficiencies
ADHD
MR

Anthopometry
Height - ht percentile, ht age, US,LS – ratio, arm span
arm span (>5cm in boys after 11yrs and >2cm in girls after 14 yrs is significant)
AS>HS – disease of vertebrae, spinal irradiation, scoliosis, marfans’,
HS>AS – Achondro,hypochondroplasia, TS??
GHD will have normal body proportions
Short stature
1. proportionate – Endocrine except hypothyroidism, rickets and genetic causes.
2. Disprop –

176
 Decreased US/LS - Short trunk in MPS, spondyepi dysplasia, CDGP (at pubertal
age), inadequate spine growth like irradiation, caries spine
Increased US/LS – Achondroplasia, rickets,hypothyroidism, ??turners
syndrome

Weight, wt percentile, wt age, (undernutrition – WA<HA)

BMI – obesity and short stature – cushings, GHD, hypothyroidism, PHP
MPH and target ht

Vitals :
Pulse, resp,
BP(percentiles)

General examination:
Pallor
Icterus
Cyanosis,
clubbing,
edema

Anemia – celiac, giardia, hypothyroidism, IBD, systemic disease esp. CKD, malnutrition
Icterus – CLD
Cyanosis – CHD, cystic fibrosis
Clubbing – CHD, CLD, IBD, TB
PE – CKD, malnutrition, hypothyroidism, turners??,
LA – TB, systemic illness??
Pulse – brady in hypothyroidism
BP – hypertension in CKD

Dental age
Gynaecomastia – on treatment with GH
Genitalia
SMR- sexual maturity rate – Tanners stage - B, P or P, TV
Micropenis
Cryptochidism
Ambiguity
Dysmorphic features:

1. GHD: Prominent forehead, frontal bossing, depressed nasal bridge, depressed midline
development(midfacial hypoplasia) hypertelorism, cleft lip/palate, crowding of teeth, single
central incisor, limited elbow extension, puffiness of face(chubbiness), high pitched voice,
Truncal obesity, normal body proportions, immature doll like face, delayed fontanelle closure,
protuberant eyes, mandible and chin underdeveloped, blue sclera, unilateral ptosis, depressed
nasal bridge, eroding of teeth
2. Turners stigmata –ptosis, hypertelorism, short neck, webbed neck, low hair line, cubitus valgus,
widely spaced nipples, pigmented nevi, short metacarpal, edema, mesomelia, strabismus,
clienodactaly

177
3. Russel silver: clienodactaly, triangular facies, café au lait spots, downturned mouth, small limbs
and hands, delayed dentition, undescended testis
4. Cornelia delange: long eyelashes, deafness, microcephaly, mental retardation, external genitalia
def
5. Seckel syndrome: craniosynostosis, bird facies, clienodactaly , disclocation of radius head, mental
retardation.
6. Blooms syndrome: dolicocephaly, malar hypoplasia, facial telengectasia, mental retardation
7. Johnson blizzard: hydronephrosis, imperforate anus, undescended testis, hypolplastic ala nasai
8. Laurence moon bardet biedel syndrome: polydactaly, syndactaly, retinitis pigmentosa, obesity,
spasticity
9. Downs syndrome
10. AHO phenotype – round face, central obesity, short 4th metacarpal, MR, hypocalcemia
11. Skeletal dysplasia:
12. kyphoscoliosis – Turners, ??PWS,
13. Rachitic features – deformity, knocked knees, bow legs, widening of wrist, pectus, rosary,
harrison sulcus, double malleoli, delayed dention
14. Cushingoid features???
15. Hypothyroidism- coarse facies, dry skin,

Malnutrition – Pellagra rash, bitots spot, xerosis,

Thyroid palpation – goiter

System examination:

CVS, RS, ABD

CNS – field cuts, PMW, myoedema, delayed relaxation of reflexes, calf hypertrophy
fundus :papilledema, optic atrophy must in suspected GHD

Summary
16. 16 year old femqle
17. Physiological/ pathological: Short stature since 5 yrs
18. Delayed puberty
19. Features of hypothyroidism
20. No features of …..

DIAGNOSIS
Case of physiological/pathological short stature, with etiology being:

DD:
1. Physiological:
1. CDGP:
2. Familial
2. Pathological:
1. Primary hypothyroidism
2. MPHD/ GHD – genetic or acquired
3. Chronic illnesses

178
 4. Turners syndrome
5. Cushings syndrome
6. PHP
7. RTA
8. IUGR related:
9. Syndromic
10. Malnutrition
11. Skeletal dysplasisa
12. Idiopathic

INVESTIGATIONS:
1. First tier
1. Hemoglobin, counts, ESR,
2. FBS, Cr, K, Ca, PO4, ALP, Alb, LFT
3. Urine routine and pH
4. stool microscopy,
5. T4 and TSH
6. Xray skull – lat view
7. Bone age –
1. Severe delay- hypothyroidism,
2. Significant delay in GHD, celiac, hypogonadism,
3. mild delay in CDGP, chronic illness
4. Appropriate in FSS, TS, downs, skeletal dysplasia, ISS
5. Second tier
1. TTG with IgA (if malabsorption suspected)
2. VBG (if RTA suspected)
3. Karyotype in girls(if turners syndrome suspected)
4. stool fat if needed
5. Skeletal survery - Xray spine, pelvis, hands for achondroplasia – only if suspected
6. Delayed puberty workup as per need (FSH if needed – if bone age >11 yrs for turners)
7. GH stimulation test – priming if needed (with normal T4)
8. 8 am cortisol (if MPHD suspected)
9. Genetics consultation if syndromic short stature suspected

Questions
1. Jaundice in Hypothyroidism
Hypothyroidism: indirect hyperbilirubinemia.

2. Jaundice in GHD
1. GH stimulates the synthesis of bile acids
2. major determinants for the induction of canalicular bile secretion.
3. Cholestasis resolves with hormonal replacement.

3. Final height outcome in hypothyroidism after levothyroxine treatment

Poor because of early fusion of the epiphyses with the metaphysis

179
4. Diagnosis of GHD
1. Growth hormone stimulation test
2. IGF-1
3. IGF-BP3
4. 12/24 hr growth hormone
5. 24hr urinary growth hormone

5. Growth hormone research society guideline (for evaluation of GHD)

1. Short stature
1. < -3SD
2. < -1.5 SD for SDH
2. Intracranial SOL/ radiation
3. MPHD
4. Features of GHD

6. Pitfalls of GH testing
1. Cut off – controversial
2. Safety issues
3. Antibody- monoclonal/ polyclonal
4. Altered in puberty/malnutrition
5. Individual variation
6. If -30 min or zero minute is high, subsequent values can be low

7. IGF-1 testing:
1. Lower diurinal variation
2. Low sensitivity
3. Higher specificity
4. If normal rules out GHD
5. If low need to do GH testing
6. Needs processing for removal of IGFBP3

8. MRI
1. If suspecting intracranial SOL
2. Polyuria
3. MPHD
4. Enlarged/ shallow sella on skull x-ray
5. Before starting growth hormone therapy

9. GH dose
1. 20-35 mcg/kg/day HS
2. Initially GV 10-15cm/yr gradually reduces
3. Stop treatment if GV less than 2 cm/yr or bone age 16yr in boys and 14 yrs in girls

10. Monitoring
1. 3- 6 monthly
2. Look for bening intracranial hypertension in first month of therapy
3. Growth response- height, weight, head circumference, pubertal status, bone
age(annually)

180
 4. IGF-1, IGF-bp3 for dose optimization
5. T4 on follow up – subclinical hypothyroidism may be unmasked
6. T4, cortisol – evolution of MPHD
7. Side effects – BIH, edema , arthralgia, SCFE, scoliosis, insulin, resistance, lower T4
with normal T3

11. Management of CDGP( reference IJPE 2012)

1. To be started after bone age more than 12 yrs
2. Testosterone 50mcg im 3 weekly for 6 months
3. E2 2.5mcg OD for 6 months
4. Ox androlone 0.05 mg/kg/day, till androgen level reach pubertal level for 3-12
months. Increases growth velocity but not final height
5. Aromatase inhibitor- letrozole 2.5mg OD with testosterone for 6 months. Slight
increase in adult height. Expensive, no strong data
6. Growth hormone no data for benefit in final height(growth velocity was better with
ox androlone). FDA approval if predicted height less than 160 cm. if CDGP is
associated with FSH growth hormone is useful. Expensive. no strong data for CDGP
alone.
7. If no onset of puberty testosterone may be repeated for 3 months. If still no onset of
puberty likely hypogonadotropic hypogonadism

12. ISS (JCM 2008)

1. Definition: height < -2SD without evidence of systemic, endocrine, nutritional or
chromosomal abnormality
2. If short for MPH i.e. < - 1.5 SD exclude FSS
3. Growth velocity less than 4 cm per year in FSS, growth velocity >/= 4cm/yr in CDGP
4. Bone age delay > -2SD, in FSS BA approx 1 yr delay in CDGP BA approx 2 yr delay
5. All routine test normal,
6. GHD, must be excluded
7. IGF-1 normal or decreased
8. IGF-1 generation test- growth hormone @ 0.1 U/kg for 5 days – IGF increases twice
9. SHOX mutation present in 5 %
10. MRI not needed

13. Management of ISS

1. Indication
1. Axological : height < - 2.25 SD, bone age delay > 2 yrs, age 5 yrs to puberty
2. Psychosocial
2. GH treatment
1. 35-50 mcg/kg/day
2. Avg height gain with 4 to 7 yr treatment is 3.5 -7.5 cm
3. Monitor with IGF-1
3. GH treatment and gonadotropin RH agonist
1. Effective if used in the last 3 yrs
2. Significant side effects
4. IGF-1
5. IGF-1 with IGF BP3

181
 6. GH and Aromatase inhibitor: used for atleast 2 yrs in peri-pubertal age. Expensive no
strong data
7. Oxandrolone increases GV no effect on final height

14. Defining response of treatment in ISS in 1st year(JCEM 2008)

1. Height SDS changed > 0.3-0.5
2. GV increase by > 3cm per yr
3. GV SDS changed >1 SD

15. IUGR/ SGA management(JCEM 2007)

1. 90% catch up 2 yr
2. Indication(FDA)
1. Age> 2yrs
2. No catch up growth by 2 yr
3. Height SD < - 2.5
3. Upto 70mcg/kg/day
4. GH therapy (pediatrics 2009)
1. Mean height gain 6 cm after 8 yrs of therapy
5. Before puberty GH 35mcg/kg/day
6. Early puberty
1. If height <140 cm then GH and GnRH
2. If height >140 cm then GH

182
16. IUGR syndromes

17. Russel Silver syndrome(hormone research pediatric 2010)

1. Presents as SGA
2. mean height gain on treatment 1.4 SDS
3. did not reach adult height
4. most height gain peri-pubertal

18. Prader- willi syndrome(JCEM 2010)

1. Low IGF-1, poor response on GH stimulation
2. Dose 20-30mcg/kg/day
3. Treatment for duration 6.9-11.5 yrs
4. Adult height gain male 1.9SDS female 1.8 SDS
5. All reach target height
6. Mortality related to lymphoid hyperplasia, obesity, volume overload

19. Noonans syndrome(EJE 2008)

1. Dose 50 mcg/kg/day
2. PTPN 11 mutation – it impacts GH response
3. Mortality associated with higher GH dose(JCM 2012)
4. Increased mortality due to bone tumor CVS disease and CNS disease

183
20. Syndromic short stature

184
21. Turners syndrome(JCEM 2003)
1. Dutch trial, 8.5 yrs mean duration, height gain 11.9-16.9 cm with a dose of 45-90
mcg/day
2. GH with oxandrolone showed height gain over 7.5 yrs
3. E2 treatment
1. If not on GH therapy at 12 yrs
2. If on GH treatment at 13 yrs
3. Can be started at any time after 3 yrs of GH therapy
4. GH + E2 started at 12 yrs should additional height gain of 5 cm(NEJM 2011)

22. Other aspects of turners syndrome(Bondi 2008)

1. CVS- coaractation of aorta bicuspid aortic wall aortic dilatation
2. Renal- malrotation, duplication, horseshoe kidney
3. Eye-strabismus, far sightedness, color blindness
4. Ear -hearing loss, sinusitis, otitis media,
5. Dental- crowding abnormal crown, enamel, dentine; early secondary dention
6. Dyslypidemia
7. Autoimmunity: 24% hypothyroidism, 6% celiac disease

23. Follow-up monitoring Turner’s

1. All ages, BP, CVS, eyes, ear every 2-5 yrs; echo/MRI whenever can be done without
sedation; if normal repeat after 5 yrs if abnormal repeat every 6 month to one yrly
2. Age < 10yrs TPO/ TTG every 2 yrs; Psychiatry, dental, ortho
3. Age > 10yrs TPO/ TTG every 5 yrs, yearly- FBG, LFT, RFT, lipids, psychiatry

24. Celiac disease:

1. HLA DQ2/DQ8…to rule out celiac disease
2. Intraepithelial lymphocytes with t-lymphocytes mediated autoantibody
3. Marsh classification
1. Infiltrative
2. Hyperplastic
3. Hyperplastic crypts with villous atrophy
4. Atrophic
4. Typically presents at 2 yrs(after weaning), they have abdominal pain, poor height and
wight gain, dylipidemia,
5. Extra intestinal manifestation
1. Iron-def anaemia
2. Short stature
3. Delayed dentition, enamel hypoplasia
4. Delayed puberty
5. apathos ulcer
6. dermatitis herpetiformis
7. arthritis
8. osteopenia, hypocalcemia
9. osteoporosis,
10. cerebral calcification
11. raised liver enzymes
12. psychiatric illnesses

185
 13. deficiency of iron, zinc, folic acid, vit d
6. associated conditions:
1. Type 1 DM,
2. turners syndrome
3. William syndrome
4. APECED syndrome
7. DD of Celiac disease IBD, IBS, cystic fibrosis
8. Treatment
1. Lifelong GFD- avoid wheat, barley and rye
2. Daily dose more than 10mg glutein is harmful
3. Supplement iron calcium vit B, zinc and fibre
4. If refractory glucocorticoids may be needed
9. Response to treatment
1. GI symtoms improve in 4 weeks
2. Biochemical, height parameters resolve in 6-12 wks
3. Antibodies normalize in 6 months

25. Histocytosis X, LCH

1. Hypothalamus, skeleton, skin, lung
2. DI> GHD> HH
3. Precocious puberty
4. accelerated growth despite growth hormone deficiency
5. hypothalamic obesity

26. Summarize normal growth velocity for children until the pubertal growth spurt.
1. First 6 months: 16 to 17 cm
2. Second 6 months: approximately 8 cm
3. Second year: just over 10 cm
4. Third year: approximately 8 cm
5. Fourth year: 7 cm
6. Later childhood until puberty (5 to 10 years): growth averages 5 to 6 cm/year

27. Summarize growth velocity during the pubertal growth spurt.

1. Maximum growth rate is 11 to 13 cm/year
2. Total growth 25 cm
3. In girls, growth spurt occurs early in puberty (breast Tanner stage II).
4. Growth spurt is later in boys (pubic hair Tanner stage III-IV, testicular volume 12-15
mL)

28. When is GH therapy discontinued?

In children with GH deficiency, the point of diminishing benefit of therapy correlates with skeletal
maturity rather than chronologic age or duration of therapy.
Therapy often is discontinued at
1. Bone age of
1. 15 years (96% of growth) or 16 years (98% of growth) in boys
2. 14 years (98% of growth) in girls.
2. Some patients with severe deficiencies may require lifelong hormonal replacement.

186
3. Skeletal dysplasias

4. What other syndromes are considered indications for GH therapy?

GH is now approved by the U.S. Food and Drug Administration (FDA) for the treatment of short
stature in the following conditions:
1. Chronic renal insufficiency before transplant
2. Turner’s syndrome (45,XO or mosaic variants)
3. Acquired immunodeficiency syndrome–related wasting syndrome
4. Prader-Willi syndrome
5. Noonan’s syndrome

187
 6. Short stature due to intrauterine growth retardation in the absence of catch-up
growth
7. Idiopathic short stature in boys with predicted adult height less than 63 inches
and girls with predicted height less than 59 inches (normal GH secretion)
Indications 2 through 6 do not require demonstration of GH deficiency
GH for treatment of idiopathic short stature remains controversial

188
Approach to adult –recurrent fractures and muscle weakness

-----yr male/female
History

Chief complaints:

1. Bone pain and bone tenderness

2. Multiple fragility fractures ---long bones, vertebrae, ribs
3. Loss of height
4. Proximal musle weakness
HOPI:
Pain-
1. Onset/ progress/sites
2. relation to moments/aggravating and relieving factors
3. tenderness
4. loss of function(movement)/ weight loss
5. inability to move/unable to work
fractures-
6. incidentally detected on radiograph
7. no preceding trauma
8. Loss of height
On enquiry
9. Proximal muscle weakness
10. Obstructed labor
11. Late Dentition, dental caries and dental abscess
Negative history :
Swelling/tumour anywhere in the body/ skin naevi
Rule out :
1. Malabsorption (Failure to gain height, recurrent diarrhea, abdominal pain)
2. Hyperparathyroidism (Polyuria, Nephrolithiasis, Abdominal pain, irritable mood)
3. Cushing’s Syndrome (Striae, plethora, recurrent bruises,DM, HTN)
4. Hypophosphatesia (foot pain, premature loss of temporary or permanent teeth, joint pains)
5. Flourosis-(water supply from shallow souce, similar history in other family members and
neighbours)
6. RTA-polyuria, muscle weakness, nephrocalcinosis
7. Renal phosphate leak- aminoglycosides/cysplatin/tenofovir/heavy metals like cadmium,
antacids containing Mg, Al, Zn
Drug History : H/o intake of calcium and Vitamin D, PO4, without response
For renal phosphate leak: aminoglycosides/cisplatin/tenofovir/heavy metals/antacids(Mg,Al,
Zn)
Family History :
1. Similar illness (to r/o AD, AR and XL hypophosphatemic rickets- 80% of familial cases)
2. Short stature, skeletal deformity suggestive of rickets / neurofibromatosis
3. Neurofibromatosis
Diet History :

189
1. Calcium
2. Sun Exposure
Personal history:
1. Menses
2. Physical activity
3. Smoking
4. Alcohol

Summary:
1. 50yrs old male
2. Recent onset bone pain and recurrent non-traumatic fractures
3. With no features suggestive of….

Examination:
1. Appearance –
1. Pain
2. Unable to sit comfortably
2. Anthropometry
Ht : Wt :
3. Vitals
4. General Examination :
1. Pallor, icterus, cyanosis, clubbing
1. Skin(e/o neurocutaneous markers) - hemangiomas /soft tissue masses/ naevi/ café au
lait/neurofibroma/nodules
2. Oral cavity- gum tumours, sinus tumors
3. Teeth (XLH/enamel hypoplasia, dental abcess, caries)
4. Features of cushing syndrome,

Skeletal Examination :
1. Appendicular skeleton- bow legs, bone deformity, malunited fractures, bone tenderness
2. Xial skeleton: kyphoscoliosis, spine tenderness

R/S :
Look for evidence of restrictive lung disease
Chest expansion, single breath count

PA: potbelly,

CNS :
Proximal myopathy with preserved reflexes: power/reflexes
Gait (Waddling)
Nutrition, tone, power, reflexes

Summary :
___ year M/F comes with H/o recurrent fractures/bone pain/proximal weakness since last ___ years
with ??loss of height, not responding to calcium and vitamin D supplements, with/without
nevi/hemangioma/soft tissue tumour

190
Probable diagnosis: Metabolic Bone Disease Osteomalacia probably secondary to hypophosphatemia

Differential diagnosis :
1. In absence of documented hypophophatemia
diagnosis For against
1. Osteomalacia –phosphopenic Bone pain, myopathy, fractures, improvement with PO4
spine deformity, height loss
2. Osteomalacia –calcpenic Bone pain, myopathy, fractures,
poor vitamin D status
3. hyperparathyroidism Bone pain, myopathy, fractures Polyuria, nephrolithiasis
4. hypophophatesia Bone pain, myopathy, fractures foot pain, premature loss of
teeth, joint pain (CPPD)
5. fluorosis Bone pain, myopathy, fractures Water source - shallow
tubewell, no similar complaints
in family members or
neighbours
6. RTA Bone pain, myopathy, fractures polyuria

b. in presence of documented hypophophatemia

diagnosis for against
1. Osteomalacia –oncogenic Recent onset, rapidly
progressive
2. ADHR
3. XLHR
4. ARHR
5. Exposure to aluminium
6. fluorosis
7. renal PO4 wasting- Cd,
aminoglycosides, cisplatin,
tenofovir
8. HHRH Low PO4, osteopenia High 1,25 (OH)D, Ur Ca
9. NPT2 mutation Low PO4, osteopenia High 1,25 (OH)D, Ur Ca,
nephrolithiasis
10. XLRH(Dent’s disease) Low PO4, osteopenia
11. prox RTA Low PO4, osteopenia
12. fanconi

Investigations:
1. First tier – Ca/PO4/ALP/ALB/PTH/25(OH)D
2. Second tier- iCa, urinary PO4 and creat/HCO3, Mg, FGF-23
3. Calculate
1. TRP= 1- (Ur.PO4*Sr. creat)/(Sr. PO4* Ur. Creat) ; Normal value=78-98%
2. TmP/GFR
4. Imaging
1. X-ray –osteopenia/ dense bone/ pseudo-fracture/coarse trabaculae

191
 2. Bone scan – super scan(multiple fracture)
3. Octreotide scan – In111
4. DOTANOC PET
5. FDG PET
6. Whole body MRI

Management:
1. PO4 – 15-60mg/kg/day usually 1-4gm /day
2. 1,25 OH D - 15-60ng/kg/day usually 1-3mcg/day
3. Surgery if localized
4. RFA – if surgery not possible
5. Octreotide – if expressing somatostatin receptor

Target
Parameter Patients value Response
PO4 Low Increase PO4
High Decrease PO4
ALP Low
High Increase PO4
PTH Low
High Increase 1, 25 OHD
Ur. Cal/Cr Low
High Decrease 1, 25 OHD
Sr. Ca Low Increase Ca supplement
High

192
Questions:
1. Mechanism of FGF 23 excess renal phosphate wasting

ARHR- DMP1/ENPP1
Normal 1,25D-9-52pg/ml

2. PO4 in circulation ?
1. 20% of the plasma inorganic phosphorus is protein bound,
2. 80% circulates as free phosphate ions HPO4 or H2PO4

3. Hypophosphatemia compensation ?
1. stimulates calcitriol synthesis via the calcium and phosphorus(duodenum and
jejunum) absorption in the intestine and enhanced mobilization of calcium and
phosphorus from bone
2. hypophosphatemia is a potent stimulator of an increase in maximal tubular
reabsorption of phosphate (TmP/GFR) by NaPT2a/2c
3. resultant increased serum calcium inhibits PTH secretion
4. low PTH subsequently increases urinary calcium excretion and increases tubular
reabsorption of phosphate (NaPT2a)
5. normal serum calcium levels are maintained and serum phosphorus levels are
returned to normal.

193
4. PO4 reabsoption: 80% of the filtered load is reabsorbed predominantly along the proximal
nephron.

5. Factors influencing Pi reabsorption in the proximal renal tubule.

Stimulate renal Pi reabsorption :
1. GH
2. IGF-I
3. Insulin
4. epidermal growth factor
5. thyroid hormone
6. calcitriol
7. dietary phosphate depletion

Inhibit renal Pi reabsorption

1. PTH (via cAMP-dependent inhibition of NPT2)
2. PTHrelated protein (PTHrp)
3. Calcitonin
4. atrial naturetic factor
5. TGF
6. Glucocorticoids

6. Definition of low phosphate <2.5mg/dl

7. Spurious low phosphate –paraprotenemia, repiratory alkalosis, post meal
8. Refeeding syndrome – low phosphate, potassium and magnesium
9. Low TMP GFR-
1. elevated PTH
2. Elevated FGF-23
3. Primary renal tubular process
10. Secondary causes of fanconi syndrome- multiple myeloma, Wilsons disease, cystinosis
11. Conditions associated with TIO- Ca prostrate, small cell carcinoma of lung, hematological
malignancy, neurofibromatosis, epidermal naevi syndrome, polyostotic fibrous dysplasia
12. Localization of TIO (NIH series) - 16/31 i.e. 61% localized
13. Failure to improve with Vit D therapy
1. Malabsorption
2. Liver disease
3. Renal disease
4. Ca deficiency

194
APPROACH TO NON TRAUAMTIC OSTEOPOROTIC VERTEBRAL/NECK OF FEMUR
FRACTURE

An old aged Male/female presented with H/o vertebral fractures/ hip fracture

Aim : to r/o primary osteoporosis vs secondary causes

H/o recurrent fractures/ bony pains/ proximal myopathy

H/o striae/ plethora/ recurrent bruises/ exogenous steroid intake
H/o polyuria/ abdominal pain/ nephrolithiasis/ constipation/ vomitting/ altered behavior/ irritability
H/o hyperthyroidism
H/o anaemia/ neuropathy/ kidney disease/ recurrent infections (e/o multiple myeloma)
H/o erectile dysfunction/ amenorrhoea/ decreased shaving frequency/ fatigue/ increased abdominal
girth
H/o recurrent diarrhea/ failure to grow/ other nutrient deficiencies (e/o malabsorption)
H/o swelling or tumour anywhere in the body

Drug History : Exogenous steroid intake

Heparin
Anti epileptics
Anti tubercular
Chemotherapy (Cyclosporine/ Tacrolimus/ Methotrexate)
Aromatase Inhibitors/ GnRH analogues
Warfarin
Aluminium containing Antacids
Proton Pump Inhibitors
TZDs

Examination: General Examination :

Ht : Wt :
Vertebral Tenderness, vertebral pain
Skeletal Examination :
E/o potbelly, kyphoscoliosis, bow legs, bone deformity
R/S :
Look for evidence of restrictive lung disease

195
Questions:
1. Radiation exposure
1. DXA: 1-10μSv
2. Natural background: 7 μSv
3. Spine radiograph: 300-400 μSv
4.
2. Least significant change
1. 2.8 x PE
2. Lumbar spine 4%
3. Femoral neck 6%
3. Explain the pathogenesis of GIOP.
Affect three phases of bone remodeling
1. Reduced absorption of calcium
2. Bone formation is impaired by
1. apoptosis (cell death) of existing osteoblasts
2. decreased recruitment of new osteoblasts
3. apoptosis of osteocytes
4. bone resorption is initially increased through various mechanisms
1. decreased production of sex steroids and osteoprotegerin
4. Who should be considered for pharmacologic therapy for GIOP?
American College of Rheumatology (ACR) recommends
1. Anyone who will receive or has received ≥ 7.5 mg/day of prednisone for at least 3
months
2. anyhigh-risk patients
National Osteoporosis Foundation recommends:
Anyone on ≥ 5 mg/day of prednisone for at least 3 months

196
Approach to Carcinoid syndrome
Management

Questions

1. DD of flushing

197
Endocrine radiology
Radiographs

1. Hyperparathyroidism
2. Jaw tumors
3. Acromegaly
4. Cushing’s syndrome
5. Rickets
6. Osteomalacia
7. Flurosis
8. Supra sellar calcification
9. Renal osteodystropy
10. Nephrolithiasis
11. Pancreatic calcifications
12. Calcification at L2 vertebra
13. Charcot’s foot
14. Vertebral fracture
15. Genu valgus
16. Genu varus
17. Wide carrying angle
18. Osteognesis imperfect
19. Dense bones
20. Paget’s disease
21. Osteoporosis
22. Thyroid mass
23. Genitogram
24. Calcified adrenal glands
25. Multiple myeloma
26. Normal sella
27. Bone age
28. Atypical fracture of femur
29. Fibrous dysplasia
30. LCH

198
Radiographs
1. Hyperparathyroidism –
1. Primary, sec, tertiary –same features of PTH excess – Bone resoprtion, osteosclerosis
is also seen in secondary only.
2. Primary hyperparathyroidism
1. Specific X-rays needed – Hands A-P view, skull lateral view, long bones,
spine, pelvis, KUB
2. General features
1. Rarefaction of bones -osteopenia
2. Prominent trabecular pattern
3. Loss of cortical definition
4. Sub-periosteal bone resorption of the outer cortex at insertion of
ligaments and tendons – phalanges – middle and prox phalanges
radial aspects symmetrically of 2nd and 3rd digits, medial metaphysic
of humerus and tibia, undersurface of distal clavicle, trochanters and
tubrosities
5. Subarticular resoption - Resorption of subarticular bone surfaces –
wide joint spaces with irregular joint margins and osteolysis –
acromioclavicular (tapering of distal one third of clavicle) ,
symphysis pubis and sacroiliac articulations
6. Osteoporosis
7. Brown tumors – osteitis fibrosa cystic – radiolucenies/lytic lesion –
central, slightly expansile, lightly septated – Classic sites – mandible,
pelvis, ribs, femora. < 2% of cases.
8. Pathologic fractures
9. Deformities

3. X-Ray hands
1. Tufting of terminal phalanges (cortical resorption) – acro-osteolysis, loss of
silver line on the terminal end
2. Classical and earliest: Sub-periosteal resorption of phalanges later
metacarpals along the radial aspects of the index, middle and ring fingers-
symmetric fraying, irregular and lace-like appearance
3. Brown cysts of metacarpals
4. Resorption of sesamoid – small size
5. Squaring of metacarpals
6. Intra cortical tunneling
7. Soft tissue calcification

4. Skull
1. Diffuse granular deossification - Salt and pepper appearance or pepper
pot skull – the texture of the bone appears granular
2. Definition of both inner and outer tables in lost
3. Punched out lesions
4. Erosion of dorsum sella
5. Loss of lamina dura – resoprtion of cortical bone around the tooth socket
6. Brown tumors - well defined
7. Ill defined cliniod processes

199
 5. KUB
1. Nephrolithiasis
2. Nephrocalcinosis

6. Vertebrae
1. Osteoporosis- rarefaction, trabecular accentuation, endplate concavities , later
fish mouth shape
2. Vertebral fractures

7. Knees – Chondrocalcinosis – menisci

8. Shoulders – Resorption of distal clavicle subchondral bone- inferior and lateral
margin.
9. Pelvis - geographic lyric lesions, thin cortex, sub articular resorption, widening of SI
joint
10. Long bone -brown tumor, lyric and sclerotic with cortical thinning, well defined
margin (geographic lesson) benign.

2. Jaw tumors
1. DD of lytic lesion
2. Brown tumor
3. DD of ossifying lesion
4. Ossifying fibroma

3. Acromegaly
1. GH excess
1. GH excess after epiphysial fusion and closure of growth plates –Acromegaly
– skeletal growth is mainly in bone width, irregular thickening of the cortex,
ectopic bone formation- spurs, bony excrescence at muscle tendon insertions
2. GH excess before epiphysial fusion – Increased linear growth –gigantism
2. D/D for acromegaly :
1. Pachydermoperiostitis – abundant periosteal new bone formation
2. Familial
3. Other D/D: Phenytoin long term therapy, lipodystrophies
4.
3. Enlargement of distal extremities with spade-like hands, squaring of phalanges,
thickening of the skin, coarse facial features, prominent PNS
4. Clubbing present
5. No signs of endochondral bone formation, normal sella, phalangeal tufts not widened,
mandible normal, joint spaces normal
6. Specific X-rays : Skull A-P and lateral view, Sella cone down view, hands, heel,
spine
7. Stimulation of periosteal bone formation- skull, long bones, vertebrae
8. Skull
1. Thickened calvaria
2. Enlarged sella with double floor appearance, ballooning of sella
3. Enlarged sinuses –Prominent paranasal sinuses and increased pneumatization of
mastoid air cells

200
 4. Prominent spuraorbital ridges and zygomatic arches
5. Protrusion of mandible – Prognathism of mandible – elongated, enlarged and
protruded, widening of the mandibular angle, malocclusion
6. Wide separation of teeth with hypercemantosis of teeth
7. Occipital protruberance overgrowth

9. Hands and feet

1. Enlarged sesamoid – Sesamoid index > 40 in men and >32 in women and increased
number of sesamoids
2. Heel pad thickness > 25 mm in men and >23 mm in women – soft tissue
quantification
3. Spurs and bony protruberances, 'Arrow head' distal phalanges,
4. Periosteal new bone formation
5. Enlarged distal phalangeal tufts – spade like deformity
6. Widened shafts - Squared phalanges and metacarpal bones
7. Beak like osteophytes at metacarpal heads
8. Widened articular spaces – cartilage overgrowth
9. Thickened soft tissue thickness at midphalanges > 27 mm

10. Spine
1. Increased vertebral body size – increased A-P and trans diameter without increase in
height in lumbar spine
2. Increased height of intervertebral disc space
3. Extensive anterior and lateral osteophytes
4. Thoracic kyphosis

11. Peripheral joints -hips

1. Wide joint space
2. Osteoarthritis
3. Bony excrescences at sites of ligaments and tendons

4. Cushing’s syndrome
1. Specific X-Rays : Spine, CXR
2. General features
1. Osteoporosis – reduced bone density
2. Thinning of bone cortices
3. Pathologic fractures – vertebrae, ribs, pubic rami
4. Deformities
5. Osteonecrosis of femoral and humeral heads –exogenous steroids

3. Spine – D-L spine - Vertebral fractures – wedge, biconcave or crush with callus at
end plates, Osteoporosis, biconcave deformities

4. Pelvis – Osteonecrosis of femoral heads, initially lytic later sclerotic

5. CXR
1. Rib fractures – multiple fractures with hypertrophic callus anterior or
posterolateral costal segments

201
 2. Increased cardiac size –fat, mediastinal widening due to fat or thymic tumor
3. Lung mass –ectopic ACTH, TB, Pneumonia, metastasis from adrenal
carcinoma

5. Rickets –
Growing bones – Inadequate mineralization of bone – growth plate is rickets i.e. before epiphyseal
fusion. Tell active/ healing also
1. X-Rays – Rapidly growing ends of bones – Growth plates – increased uncalcified osteoid –
lucency
2. Wrists, knees, hips –proximal femur, ankles – increased lucency between metaphysis and
epiphysis. Absent zone of provisional calcification
3. rachitic rosary anterior ends of ribs – swelling of costochondral junctions bulbous
enlargement of costochondral junctions
4. Widening of metaphysial growth plates, splaying, fraying (piant brush appearance) and
cupping (cup like) of metaphysic
5. Irregularity of epiphyses-fraying
6. Generalized osteopenia
7. Coarse trabecular changes
8. Healing stage – Space between epi and metaphysis reduces
Bowing deformities, fractures, scoliosis, pseudofractures

1. Differential for leg bowing in children:

1. developmental or congenital bowing
2. Blount disease
3. osteogenesis imperfecta

2. Differential for widening of the growth plate(splaying)

1. scurvy
2. delayed maturation due to illness
3. growth hormone excess
4. hyperparathyroidism
5. hypothyroidism
6. Osteopetrosis

3. Differential for flaring of the metaphysis:

1. anaemia(s)
2. fibrous dysplasia
3. storage diseases
4. chronic lead poisoning
5. Schmid metaphyseal dysplasia - deficiency of COL10A1

4. Healing:
1. first evidence: is a reappearance of the provisional zone of calcification
2. healing progresses: the metaphysis becomes mineralised from the shaft toward the
epiphysis, ultimately resulting in radiographic continuity of the shaft with the
provisonal zone of calcification

202
5. Differential diagnosis
1. Cupping- trauma/ dysplasia/scurvy
2. Fraying DD hypophosphatasia/chronic stress/ decreased copper
3. Splaying
4. Wide growth plate
5. Looser zone
6. Uncalcified subperiosteal osteoid
7. Radiolucent metaphyseal bone-healing
8. Rachitic rosary
9. Bowing
10. Triradiate
11. Croniotabes

6. Rickets Mimics
1. Hypophosphatasia
2. Metaphyseal dysplasia(SCHMID)

7. Changes in diaphysis
1. Coarse trabecular
2. Cortical thining
3. Loozer’s zone
4. Curvature of shaft of long bone

8. Osteomalacia –
1. Inadequate mineralization of bone after growth complete and post epiphysial fusion
2. Adults – pseudofractures/ Looser zones/ Milkman syndrome/ increment fractures –
Insufficeincy fractureshealing with uncalcified osteoid, fibrogenic imperfect ossium
1. Linear translucencies
2. Bilateral symmetrical – Predictable locations- Femoral necks, pubic and
ischial rami. Ribs, axillary margins of scapulae
3. Perpendicular to the cortex, concave surface
4. Absence of surrounding sclerosis or callus
5. Also seen in other bone softening disorders – Paget’s disease, fibrous
dysplasia, rickets, hypophosphatasia
6. Surrounding sclerosis or callus
3. Decreased bone density/increased bone density(hypophosphatemia)
4. Coarse trabecular pattern
5. Deformities
1. Triradiate pelvis, protrusion acetabulae deformity, bowing of femur and
tibiae, kyphoscolisosis, sterna abnormalities
6. Loss of cortical definition

7. Fluorosis- >2 ppm – tooth enamel mottling and generalized increase in bone density
1. Diffuse Osteosclerosis – generalized increase in density more in axial skeleton than
appendicular skeleton
2. Ligament calcification – interosseous membrane calcification
3. Sacrospinous ligament calcification and sacrotuberous ligament calcification

203
4. Supra-sellar calcification – Causes
1. Craniopharyngioma
2. Meningoma
3. Dermoid cyst
4. Germinoma
5. Renal osteodystrophy
1. Hyperparathyroidism – Tufting of terminal phalanges, phalangeal resorption – sub-
periosteal resorption of the radial aspects of the phalanges
2. Sclerotic bones – Osteosclerosis – vertebrae, pelvis
3. Rugger jersey spine – sclerosis of the end plates of vertebrae and normal lucency in
the midvertebral bodies
4. Soft tissue calcification – ocular, arterial, cartilaginous, soft tissue
5. Osteomalacia – Looser zones – wide, straight bands of translucency perpendicular to
and abutting the bony cortex, usually symmetric with narrow area of sclerosis

6. Nephrolitiasis

7. Pancreatic calcification

8. DD of calcification at L2 vertebra

1. Charcot’s foot
1. Initial plain x-rays are negative for a few
days up to 3 weeks
2. Only finding in acute COA is soft tissue
swelling
3. Chronic
Atrophic—
1. bony resorption and little
fragmentation
2. Pencil pointing or sucked
candy deformities
3. Metatarsal heads and shafts
Hypertrophic/Proliferative—
1. bony proliferation and
destruction of joints,
fragmentation and new bone

204
 formation
2. More common type
3. Larger joints of the foot
(mid-foot and rear foot)
1. Osteophytes, subchondral sclerosis and
narrowing of joint spaces
2. Forefoot lesions include
demineralization, bone destruction &
periosteal reaction—mimicking
uncomplicated osteomyelitis

4. Vertebral fracture

Osteoporosis
Site: mid thoracic, thoraco lumbar
Very uncommon site: above T4
Vertical trabeculae prominant

5. Genu valgus

6. Genu varum

7. Wide carrying angle

8. Osteogenesis imperfecta
1. Multiple fractures
2. Different age of healing

205
 3. Diaphyseal
4. DD:
1. Battered baby syndrome – metaphyseal fractures

9. Dense bones
1. Fluorosis
2. Prostate Ca with osteoblastic metastasis
3. Osteopetrosis: Skull radiographs
typically show
1. thick dense cranium with basal
osteosclerosis
2. under-pneumatisation of the
paranasal and mastoid sinuses
3. alternating dense and lucent
bands
4. Renal osteodystrophy
5. Paget’s disease

6. Paget’s disease
1. Thickened disorganized trabecular and cortical pattern –radiologic features depend on stage of
disease and bone affected
1. Lytic stage ----mixed stage –lysis + osteoblastic ----- sclerotic stage
2. Features
1. Changes in bone density –Patchy sclerosis – Thickened cortex
2. Coarse trabeculae
3. Bone expansion
4. Increased or decreased density
5. Subarticular extension
6. Deformity – bowing
7. Osteosclerosis -disorganized
8. Pathologic fractures
9. Pseuodfractures
3. Sites
1. Pelvis
2. Femur
3. Skull – Marked calvarial or vault thickening, cotton wool opacities –fuzzy poorly defined
areas of sclerosis
4. Tibia
5. Spine Vertebra –Ivory vertebra/ picture frame vertebra -Lumbar
6. Proximal long bones

7. Osteoporosis
1. DXA early
2. General radiologic features – Late feature – Spine - Increased radiolucency, reduced vert body
density, cortical thinning, altered trabecular patterns –prominent vertical trabecular pattern,
fracture deformity

206
8. Thyroid mass - cervico thoracic sign

9. Genitogram
1. retrograde cystography is performed after
insertion of an 8-F Foley catheter in the
anterior perineal orifice
2. followed by controlled-pressure
retrograde injections along the urethro-
vaginal route

1. persistent urogenital sinus and a normal

vagina (arrow)
2. presence and the size of the vagina
should be carefully assessed, along with
the presence or absence of the cervical
imprint on the vaginal dome
(arrowheads), which are usually present
in CAH because mullerian structures
differentiation is not impaired
3. configuration of the urethra (small arrow)
indicates a male type urethra.
1. Oblique view of genitogram shows the
elongated, but female-type urethra
2. contrast pooling in the right inguinal
region (arrow) indicating free
communication between the uterus and
the peritoneal cavity
3. consistent with at least one patent
fallopian tube
4. The vagina is distended by contrast

5. Calcified adrenal glands

1. Wolman’s disease – punctuate calcification with hepatoslenomegaly
2. Adrnal hemorrhage
3. ACC
4. Neuroblastoma
5. myelolipoma

6. Multiple myeloma

7. Normal sella
1. AP – 17 mm, depth – 15 mm, width – 16 mm
2. True lateral view

207
8. BONE AGE assessment
1. X-Ray of left hand with wrist – Carpals, epiphysis of distal radius/ ulna, epiphysis of phalanges
2. Congenital hypothyroidism: Epiphysis of femoral head, tibial epiphysis
3. Delayed bone age
1. Normal –within 2 SD
2. Mild delay – Systemic disease, GHD
3. Moderate delay - CDGP
4. Severe delay – Hypothyroidism

9. Atypical fracture of femur

10. Fibrous dysplasia

11. LCH
1. 80% to 100% of LCH patients
2. Skull, the long bones, and the flat
bones
3. Painful swelling
4. irregularly marginated lytic lesions of
bone
5. Peripheral sclerosis: sign of initial
healing

6. Chondrocalcinosis

208
DD
1. Hemochromatosis
2.

209
CT scan
1. Adrenal mass
2. Thyroid neoplasm
3. Basal ganglia calcification
4. Pancreatic calcification
5. Carcinoid with hepatic metastasis
6. Pancreatic mass
7. Emphysematous pyelonephritis
8. Mediastinal mass
9. Fibrous dysplasia
10. Lung tumor
11. Skull metastasis

1. Adrenal mass – contrast arterial, venous and delayed phase

1. Unilateral
1. Adenoma
1. <10 HU
2. < 4 cm
3. absolute percent washout > 60%,
4. relative percent washout > 40%
5. Smooth
2. Pheochromocytoma
1. calcification – 10%
2. Heterogenous
3. Well defined/fat planes +/-
4. Involvement of vessels
5. Sensitivity 95%, specificity70%

210
 Genetic testing
1. Catecholamine secreting abdominal paraganglioma-sequence of mutation testing;
SDHB>SDHD>VHL
2. Most common cause of inherited paraganglioma of head and neck are PGL- order of testing
recommended; SDHD>SDHB>SDHC>VHL&RET
3. >40 YEARS –SDHB mutation
4. Malignant disease –SDHB

1. Carcinoma –
Contrast-enhanced imaging often demonstrates heterogeneous, predominantly irregular peripheral
enhancement with central nonenhancing areas secondary to hemorrhage or necrosis
1. heterogenous lesion –
1. hemorrhage – increased attenuation
2. necrosis- attenuation
3. calcification in 30% – high attenuation
2. often larger than 6 cm
3. hepatic, lung and lymph node mets
4. invade other organs
5. involvement of renal veins and IVC - 9% to 19%
6. bilateral in 2- 10 %

211
 2. Metastasis – Primary from
1. Lung
2. Kidney
3. Colon
4. Breast
5. Esophagus
6. Pancreas
7. Melanoma
3. Myelolipoma/lipoma
4. Lymphoma
5. Adrenal cyst
DD –
1. cystic ACC
2. cystic pheochromocytoma
3. bronchogenic
4. retroperitoneal cyst

212
 1. Old Hemorrhage
Incidentaloma
1. Cushing’s syndrome – 5%
2. Pheochromocytoma – 5%
3. ACC – 4.7%
4. Primary hyperaldosteronism – 1.5%

DD of adrenal lesion greater than 4 cm:

1. ACC
2. large ACA
3. myelolipoma
4. adrenal metastasis of another cancer
5. pheochromocytoma
6. adrenal cyst
7. ganglioneuroma
8. sarcomas
9. lymphomas

1. Bilateral
1. Tuberculsosis
1. Early tuberculous adrenalitis
–bilateral adrenal
enlargement with a central
necrotic area of
hypoattenuation and a
peripheral enhancing rim
2. In the healing stage - adrenal
glands become calcified and
atrophic

2. Histoplasmosis
1. Most characteristic –
1. bilateral symmetrical
enlarged
2. low density areas of
focal hemorrhage and
necrosis
3. peripheral
enhancement
Range of CT findings
1. Minimal enlargement with faint
flecks of calcium
2. Moderate enlargement with focal low
attenuation nodules
3. Massive enlargement with large areas
of necrosis or dense calcification
Changes are bilateral and symmetrical
Adrenal gland shape usually preserved
Rx:

213
1. AmpB: .5mg/kg/day in 4 divided
doses , to be given slowly in glucose
solution over 4-6 hours
Total dose -3-4 gm
2. liposomal AmpB 3-5 mg/kg/day
3. Itraconazole: 200 mg BID
4. voriconazole
5. posaconazole

6. Metastasis
1. Lung
2. Breast
3. skin (melanoma)
4. kidney
5. thyroid
6. colon

7. Pheochromocytoma

8. Old hemorrhage

9. Lymphoma
1. Homogenous
2. Less enhancing

10. BMAH

214
1. Thyroid neoplasm
Normal thyroid – 125 HU, homogenous
1. Encasement and narrowing of surrounding structures – trachea, carotids
2. Extent in to superior mediastinum
3. Extension into veins - IJV
4. Vocal cord paralysis
5. Tear drop sign- compromised vascular lumen
6. PTC – lymph node calcification
7. Calcification:
1. Micro – PTC
2. Macro – MTC

8. Basal ganglia calcification

1. age-related calcifications
2. toxic
1. carbon monoxide poisoning
2. lead poisoning
3. mineralizing microangiopathy
4. radiation therapy
5. chemotherapy
6. radiation therapy
7. chemotherapy
3. infectious
1. TORCH
2. CNS tuberculosis
3. AIDS
4. neurocysticercosis
5. CNS toxoplasmosis
4. metabolic
1. hyperparathyroidism
2. Hypoparathyroidism
3. Pseudo hypoparathyroidism
4. Hypothyroidism
5. Fahr disease

215
5. Pancreatic calcification

6. GI carcinoid with hepatic metastasis

1. Most commonly involves – ileum
2. Desmoplastic reaction – pulls mesentry

7. Pancreatic neoplasm
Pancreatic phase scan:
Tracking method Simple time based Look for
Arterial Aorta > 100 HU 15 -35 sec Hypervascular
tumor - insulinoma
Pancreatic After 6 sec 35-55 sec Adeno Ca
Portal After 13 sec 60-80 sec Metastasis

1. Glucagonoma
1. Large
2. Tail
3. Metsastais
4. 80% - malignant
2. Gastrinoma
1. Triangle
3. VIPoma

4. Non functional
1. 90% - malignant

216
 5. Insulinoma: 0.5 to 0.6 mm sections in arterial phase
1. arterial phase: hypervascular
tuomar like insulinoma
2. Pancreatic/portal phase -
pancreas bright, lesion iso intense
3. Hypervascular/small
4. 85% functional
5. 15% non functional
6. 10% malignant
Labs:
1. symptoms, signs,or both with
glucose < 55mg/dl
2. insulin > 3.0 μU/ml (18 pmol/l)
3. C-peptide > 0.6 ng/ml (0.2
nmol/l)
4. proinsulin > 5.0 pmol/l
5. β-hydroxybutyrate < 2.7 mmol/l
6. increase in glucose > 25 mg/dl
after glucagon

1. Emphysematous pyelonephritis (EPL)

Classification:
Grade I: involving pelvis
Grade II: involving parenchyma
Grade III A:-perinephritic space involved
B:- Paranephritic space involved
Grade IV: B/L involvement or solitary kidney with EPL

2. Anterior/superior mediastinal mass

DD
1. Thymoma
2. Thymic carcinoid
3. Parathyroid adenoma

217
 Fibrous dysplasia

4. Lung tumor
Endocrine manifestations
1. Cushing’s syndrome
2. SIADH

1. Skull metastasis

218
MRI
1. Pituitary mass
2. Empty sella
3. Hypothalamic mass
4. Grave’s opthalmopathy
5. Adrenal mass
6. Vertebral fracture
7. Diabetic muscle infaction
8. Biconcave vertebrae
9. AVN femur
10. Mucormycosis
11. Foot osteomyelitis
12. Charcot’s foot
13. Septo-optic dysplasia

T1W
1. white matter – white; grey matter – grey
2. bright – fat , acute blood, melanin, melanin, high protein fluid, soft calcification, posterior
pituitary

T2W
1. white matter – grey; grey matter – white
2. bright – subacute blood, fluid, pituitary tumor
FLAIR – T2W with fluid suppred
FATSAT/STIR – T1W with fat suppresed
DWI-
Chemical shift -In phase out phase – 2.2 msec in, 4.4 msec out

1. Pituitary mass
1. T2 hyperintense – heterogenous or homogenous, Cystic changes
2. Hemorrhage – T1 hyper intense, confirm with gradient-echo (GRE) images – hypo
intense
3. DWI -
4. Cavernous sinus invasion
5. Optic chiasm splayed
6. Encases but does not narrow ICA (check caliber)
7. Ventricles compressed
8. figure of 8/ snowman appearance
9. posterior pituitary bright spot
10. Dynamic scan
1. 8 – 15 sec scans, 8-10 times
2. Delayed phase enhancement and washout
11. Contrast:10 ml gladonium

12. DD
1. Craniopharyngioma

219
 1. Cystic, calcification
2. Major component suprasellar
3. T1 hyperintense – protein rich
machenanry fluid
4. Bimodal age

1. Meningoma
1. T2 hypo/isointense
2. Dural tail sign
3. ICA encased and compressed
2. Ratke’s cleft cyst
1. T1 hyperintense
3. Arachnoid cyst
1. Like CSF - T1 hypointense, T2 hyperintense, FLAIR - suppresed
2.
4. Epidermoid cyst
1. T1 hypointense, T2 hyperintense, FLAIR –not suppresed
5. Dermoid cyst
1. T1 hyperintense
2. Midline
6. Apoplexy
Radiology: Clinical features:
Rim enhancement Headache
Heterogenous Common – PP Hemorrhage
Vasospasm due to hypotension

7. Hypophysitis
Radiology: Clinical features:
Enlarged pituitary Young females –late pregnancy or post
Thick stalk (> 3 mm) partum
Enhanced on Gd contrast (more than F:M – 9:1
cavernous sinus) ACTH or TSH deficiency with normal Gh
Empty sella – later or Gn
Size usually < 6 cm3 Pituitary Ab upto 70% of cases
Homogenous, rarely heterogenous

2. Wilson Hardy classification

1. Extension
2. Suprasellar extension
1. 0: none
2. A: expanding into suprasellar cistern

220
 3. B: anterior recesses of 3rd ventricle obliterated
4. C: floor of 3rd ventricle grossly displaced
3. Parasellar extension
1. D: intracranial (intradural); specify (1) anterior (2) middle, or (3)
posterior fossa
2. E: into or beneath cavernous sinus (extradural)
4. Invasion / Spread
5. Floor of sella intact
1. I: sella normal or focally expanded; tumor <= 10mm
2. II: sella enlarged; tumor >= 10mm
6. Sphenoid extension
1. III: localized perforation of sellar floor
2. IV: diffuse destruction of sellar floor
7. Distant spread
1. V: spread via CSF or blood-borne

221
1. Empty sella

1. DD
1. Idiopathic
2. Sheehahan’s
3. BIH
4. Vasculotoxic snake bite
5. Previous radiation,
surgery or chemotherapy
6. Tumor apoplexy
2. Elster rule – normal pituitary
gland height
1. Child – 6 mm
2. Male and post
menopausal female – 8
mm
3. Child bearing female –
10 mm
4. Pregnant female – 12
mm

1. variable clinical conditions:

1. asymptomatic arachnoid pouch
2. severe intracranial hypertension
3. rhinorrhea
4. hypopituitarism
5. hyperprolactinemia
2. symptomatic intracranial hypertension:
CSF shunting

3. Hypothalamic mass
1. Hamartoma
1. T1 isointense, T2 isointense

222
 2. Non enhancing
3. Arises between tuberum cinerum and
mamillary bodies

1. Granulomatous lesion

1. LCH
2. Sarcoidosis
3. Wegener granulomatosis
4. Tuberculosis
5. Germinomas
6. Leukemia
7. autoimmune
infundibuloneurohypohysitis

8. Grave’s opthalmopathy
1. Sequence of muscle involvement – IMSLO
2. Extra orbital fat involved
3. Coke bottle sign
4. DD
1. Orbital pseudotumor
2. Sarcoidosis
3. Pseudotumor
4. Metastasis

9. Adrenal mass
1. Adenoma
2. Carcinoma –
1. ACCs appear isointense to hypointense relative to liver parenchyma on T1-
weighted images and hyperintense relative to liver parenchyma on T2-
weighted images
2. hemorrhage - high signal intensity on T1-weighted images
3. necrosis - high signal intensity on T2-weighted images
4. On chemical-shift MRI, the presence of intracellular lipid can cause regions
of signal loss (<30% of lesion) on out-of-phase images relative to in phase
images

3. Pheochromocytoma
1. Identify> 95% of tumors; Sn 93-100% for adrenal tumor

223
 2. Superior to CT for extraAdrenal tumors
3. T1-signal similarly to liver, kidney, muscle
4. T2- bright because of increased vascularity
5. Chemical shift- opposed phase: no signal loss
6. SN(extra adrenal, mets, recc)-90%
7. SP: 70%
4. Myelolipoma/lipoma
5. Metastasis

10. Vertebral fracture

1. Osteoporosis
1. Below T4
2. Multiple vertebrae
3. Flute sign – T2 bright line
4. Inphase outphase (↓)
5. Chronic – marrow fat and fluid
filled cavity
6. T1 hypointense fracture line
7. Preservation of trabeculae on CT
scan

2. Multiple myeloma
1. Variegated appearance
2. T1-weighted sequence lumbar
spine: diffuse permeative low
signal
3. T2-weighted STIR: diffuse high
signal

3. Metastasis
1. Above T4
2. Posterior surface convex
3. Pedicle or posterior elements
involved
4. Soft tissue mass or swelling
5. Epidural mass
6. DWI – restriction
7. Inphase outphase (↑)

4. Acute
1. Edema in T2 fat suppressed images
2. Symptomatic
3. Responds to percutaneous
vertebroplasty or ballon
kyphoplasty
5. Chronic
1. No edema
2. Asymptomatic

224
1. No benefit with procedures

225
 11. Diabetic muscle infarction
T1-WI:
1. enlargement or fullness
2. obscured fascial planes
3. Involved areas : isointense
4. tiny foci of hyperintense signal
consistent with foci of hemorrhage
T2-WI:
Increased signal within the affected muscle
consistent with intra-muscular edema and
inflammation

Absence of a

c
Management
1. Resolves by itself
2. Bed rest
3. Adequate analgesia
4. Tight metabolic control
5. Gentle Physiotherapy after the initial
phase
6. In case of large necrotic masses,
conservative resection of necrotic
debris indicated.

226
7. Biconcave vertebra
1. DD
1. Severe osteomalacia
2. Severe osteoporosis
3. Sickle cell disease – H shaped vertebra
4. Gaucher’s disease

8. AVN femur
1. Double line sign

9. Mucormycosis

10. Foot osteomyelitis

STIR and T1W images in Charcot arthropathy with a plantar ulcer (asterix) and osteomyelitis of the
cuboid

Contrast enhanced images with and without fat saturation: Enhancement of the cuboid bone and
adjacent soft tissues on postcontrast images, with the plantar ulcer, makes osteomyelitis very likely

227
11. Charcot’s foot

No osteomyelitis in chronic
Charcot arthropathy as there
is no marrow edema

Ghost sign: Indicative of

arthropathy with
osteomyelitis
Poor definition of the
margins of a bone on T1-
weighted images, which
become clear after contrast
administration

12. Septo-optic dysplasia (De Morsier syndrome)

1. "point down" appearance of

the lateral ventricular frontal
horns on coronal images
2. absent septum pellucidum
3. hypoplastic pituitary stalk
4. hypoplastic optic chiasm/optic
nerves and globes

228
USG
1. Thyroid mass
2. Parathyroid mass
1.
1. Thyroid
7 -12 Hz, linear probe

1. Parathyroid adenoma –
USG--65%sensitive, 95%specific
Sestimibi 45-90% sensitive; 98% specific
10 Hz probe
Adenoma: hypoechoic(sonolucent)
Thyroid: echo dense, 75% of adenoma
Non- invasive technique localize in repeat
surgery
Disadvantages
1. Operator dependent accuracy
variable
2. Fail gland is in tracheoesophageal
groove
3. Failgland is in anterior
mediastinum
4. Will pick up only dominant gland
(generally) in multigland hyperplasia

229
 Nuclear Medicine
1. Thyroid scan
2. Parathyroid scan
3. MIBG
4. WBI scan
5. MDP bone scan
6. Gastric emptying
7. FDG PET
8. DOTANOC scan
9. Octreoscan
10.

1. Thyroid scintigraphy with Tc99m pertechnetate –

2-5 mCi i.v. – scan at 20 minutes.
Normal uptake via NIS – Thyroid, salivary glands, gastric mucosa, lactating breasts, oral mucosa and
nasal mucosa. T 1/2 -6 hours.
Excreted by kidney and ureter
Most commonly used agent for thyroid scan – short t1/2. Cheap, easily available, only gamma, no
beta rays, ideal photon wavelength for sharp images, least radiation and I123 not easily available as
needs on-site production. Taken up by NIS – pertechnetate is analog of iodine.
1. Increased radiotracer uptake in diffuse symmetric homogeneous distribution in thyroid both lobes
without cold nodules and absent uptake in salivary glands - Depends on clinical setting –
D/D –
1. Graves’ disease (Thyrotoxic, Eye signs)
2. Recovering phase of thyroiditis (History,
usually TSH elevated)
3. Iodine deficiency – Increased NIS
expression
4. Some cases of Hashimoto’s thyroiditis -
hypothyroidism

5. Reduced uptake
1. Thyroiditis

230
2. Unilateral uptake

3. Absent tracer uptake in thyroid bed with normal salivary gland uptake – D/D based on clinical setting
1. Thyrotoxic patient – Thyroiditis, iodine induced
thyrotoxicosis, factitious thyrotoxicosis
2. Total thyroidectomy status –benign or malignant
condition
3. Post RAI ablation
4. Drugs – T4, ATDs – decrease uptake, Iodine
contrast, amiodarone, iodine
5. Congenital thyroid agenesis

6. Absent tracer uptake in thyroid bed, salivary gland and gastric bed-NIS defect

1. I123: 0.1-0.6mCu- scan between 4 to 24 hrs

2. Risk of thyroid malignancy if dose > 20 rad

1. Parathyroid imaging
99 Tech Parathyroid scan(sestamibi)
1. Early: 20 min
2. SN: 45-90%, SP: 98%
3. Concentrated in mitochondria
4. Neg scan: decrese chances for successful
surgery (93% vs 100%)

2. SPECT-CT
1. Increase SN:85%

3. Whole body MIBI scan

MIBG

1. Agents: I133/I 123

2. Alternatives: FDG PET/ F-flurodopamine/f-dihydropheylalamine/octreoscan
3. Useful: small tumor/unsual location
4. SP for Pheo approximately 100%
5. Other tumors: chemodectomas, non-secretory paragangliomas, carcinoid, MCT; Mets: SN123I (70%)
6. SN: 123I(95%)> 131I (85%)
7. T ½ 123I: 13 hr; 131I : 8.2 days
8. Adv of 123: increase SN/ increase dose/ SPECT possible

231
9. Block thyroid: SSKI-100mg BD x 7 days
10. Normal uptake: normal adrenal gland (75%), myocardium, spleen, liver, bladder, lung, salivary gland,
colon, cerecellum
11. Adverse effects: thrombocytopenia
12. Scan time: 24hrs 48 to 72hrs

I131 scan: whole body radioiodine scan

1. Preparation
1. Stop LT4 for 1 month OR recombinant TSH
2. 5 miCu of I131 and scan after 48 hrs
3. SPECT/CT may be done
2. Ablation
1. 50 to 200 miCu
2. once safe level achieved patient may be discharged
3. steroid cover required if metastasis to brain spinal cord or lung

Bone scan(MDP)

4. Indications
1. Metastasis

2. Fibrous dysplasia

3. Paget’s disease

232
 1. Preparation
1. 20miCu Tc99
2. Scan after 3 hrs
3. Whole body projection taken
4. SPECT/CT may be done
2. Localize:
1. Increase blood flow
2. Increase rate of bone formation
3. Super scan: increased tracer uptake in axial and appendicular skeleton,
reduced soft tissue uptake, poor or absent renal images, prominent
costochondral junction and 'tie' sign in sternum
1. metabolic bone scan
2. fluorosis

Gastric emptying scan

233
1. FDG PET
1. Preparation:
1. 10miCu F18DG
2. Scan at 60min
3. If SUV max>2.5 suggestive of malignancy, acute fracture
1. Insulinoma

2. Pheochromocytoma
1. 6-F flurodopamine PET(NIH): good for mets
18
2. F fluro dopa: mets
18
3. F dihydro P.A.
11
4. C hydroxyephedrite
11
5. C epinephrine
6. FDG PET: undifferentiated tumor; SDHB
―warburg effect‖= SDHB loss tumor cells shift from oxidative phosphorylation to aerobic
glycolysis increase glucose requirement

4. Ga68 DOTANOC PET

60 minutes after injecting 150 MBq 68 Ga DOTANOC
1. Indications
1. Cushings syndrome

2. Tumor induced osteomalacia

234
3. Carcinoid/GI NET

2. Physiological uptake
1. Pituitary
2. Liver
3. Spleen
4. Adrenal
5. Kidney, Ureter
6. i.v. canula insertion site
1. SUV-propotional to receptor expression
2. Lesions picked up:
1. Tumor
2. Fractures
1. Images
1. Max uptake images
2. Coronal images
3. CT images

4. Octreoscan(somatostatin receptor scintigraphy)

1. Uses: metastatic pheochromocytoma

235