ENDOCRINE DISORDERS

ADRENAL GLAND DISORDERS

Adrenal Gland A&P

2 glands on top of each kidney w/ 2 parts:

o adrenal cortex = produces steroid hormones (glucocorticoids, mineralcorticoids, adrenal androgens)
o adrenal medulla = produces E/NE
ACTH/ cortisol are released in pulsatile pattern in response to stress, exercise, surgery, hypoglycemia

DISEASE

CAUSE

Addisions Disease
(Hypocortisolism)
Primary Adrenal
Insufficiency

Dysfxn/ absence of
adrenal cortices
2.6:1 F:M ratio
onset = 3050 y/o

Secondary Adrenal
Insufficiency

Acute Adrenal
Insufficiency
(Adrenal Crisis)

Congenital Adrenal
Hyperplasia (CAH)

SIGNS/SYMPTOMS

Autoimmune adrenalitis
M/C
Adrenal hemorrhage
Metastatic malignancy/
lymphoma
Infection: TB, CMV, fungi
Amyloidosis
Hemochromatosis
Congenital Adrenal
Hyperplasia (CAH)
Familial glucocorticoid def &
hypoplasia
Drugs ketoconazole steroid

Exogenous glucocorticoid
therapy= M/C/C
Defect in hypothalamuspituitary axis
ACTH def

Occurs in pts w/ Addisons

Disease precipitated by:
o Infection
o Surgery
o Dehydration to due salt
deprivation, vomiting,
diarrhea

Autosomal recessive trait

deficiency in enzymes
necessary for synthesis of
cortisol = dec cortisol level

LAB/DX

Weakness, fatigue, anorexia, wt

loss
Hyperpigmentation= diffuse
tanning over nonexposed/exposed areas,
most prominent over jts/
posterior neck
Dizziness, orthostatic
hypotension
N/V
Salt craving
Amenorrhea
Loss of axillary/ pubic hair

Usually chronic & nonspecific

manifestations
Weakness, lethargy, easy
fatigability, anorexia, nausea,
myalgia, menstrual disturbances,
wt loss, hypotension, skin
changes
Hx of steroid therapy
Hypotension
Fever
Dehydration
Abd pain
N/V/ anorexia
Weakness
Depressed mental status
Hypoglycemia
Shock/ coma death in
untreated patients
@ birth female w/ ambiguous
external genitalia
primary amenorrhea

TREATMENT

Low AM cortisol level < 3

mcg/dL @ 8 am = diagnostic
Hyponatremia
Hyperkalemia
Normocytic normochromic
anemia
Azotemia
DX = ACTH stimulation test
no change in cortisol level
from baseline
CT scan of abd evaluate
adrenal glands
Decreased DHEA levels
Plasma ACTH level high
(usually >200)

Hyponatermia
Normocytic normochromic
anemia
ACTH provocation test
Plasma ACTH will be
normal/ low

Eosinophil count usually

high
Hyponatremia/ hyperkalemia
or both present
Dx made by ACTH
stimulation test
markedly elevated ACTH >
200

increased levels of ACTH

adrenal hyperplasia
high level of AM 17
hydroxyprogesterone

Life long glucocorticoid

therapy
Hydrocortisone BID
Fludrocortisone AM to
replace mineralcorticoid
component
Pt should wear alert
medical bracelet

** double/ triple steroid doses

during stressful situations
(cold/fever), trauma, surgery

Life long glucocorticoid

steroid therapy
Hydrocortisone oral only

** double/ triple steroid doses

during stressful situations
(cold/fever), trauma, surgery

IV hydrocortisone
IVF
Correction of
hypoglycemia w/ glucose
IV
Broad spectrum ABx

prednisone replacement
life long

Common in infancy/
childhood

Cushings Syndrome
(Hypercortisolism)
(consideredCushings
Diseasewhen specific type
of Cushings syndrome is
due to excessive pituitary
ACTH secretion from
pituitary adenoma)

M/C = 21hydroxylase

lack of development of
secondary sexual characteristics

Pituitary adenoma (Cushings

Disease)= M/C 70%
non pituitary neoplasm
(ectopic ACTH) 1520%
M/C seen in pts w/ SCC of
lung
iatrogenic overuse of steroids
adrenal neoplasm
(adenoma/carcinoma)
nodular adrenal hyperplasia
tertiary hypercortisolism

central obesity effecting

face, neck, trunk, abd
moon faces/ buffalo hump
easy to bruise, facial plethora,
red purple striae, acne
hirsutism
HTN
Hyperglycemia
Gonadal dysfxn inc androgens,
amenorrhea, infertility, dec
libido
Poor concentration/ depression
Muscle weakness
Osteoporosis
Renal calculi from steroid
induced hypercalcemia

Elevated cortisol
CBC elevated H&H, RBC
Low potassium
Fasting hyperglycemia
TO DIAGNOS
o Elevated AM cortisol
o Dexamethasone
suppression test
cortisol > 5 mcg/dL
o 24 hour urine collection
for free cortisol = high
o Midnight salivary
cortisol test elevated =
diagnostic
Pituitary MRI
Chest CT to r/o SCC
Abd/ pelvic CT to r/o adrenal
tumor

Cushings disease
removal of pituitary
adenoma
Ectopic ACTH syndrome
spironolactone,
ketoconazole, metyrapone,
aminoglutethimiate
Adrenal adenoma
unilateral adrenalectomy or
laparoscopic adrenal
surgery
Adrenal carcinoma
mitotane, ketoconazole,
metyrapone &
aminoglutethimiate RAD/
chemo not successful poor
prognosis

** untreated Cushings is
frequently fatal

Hirsutism/ Virilism

Hirsutism:excessive
terminal hair growth that
appears in male pattern in a
female
Virilism:increased
muscularity, deepening of
voice, clitoromegaly

Hyperaldosteronism

Excessive secretion of
aldosterone inc Na
reabsorption/ loss of K+/
H+

Excessive adrenal/ ovarian sex

hormones
High levels of DHEA,
DHEAS, testosterone
Idiopathic familial
PCOS, menopause, androgen
producing ovarian tumors
Cushings syndrome
Adrenal carcinoma/ tumors/
CAH
Anabolic steroids, danazol,
minoxidil, progesterone
Severe insulin resistance,
hypothyroidism, acromegaly

Primaryadenoma of
hyperplasia of adrenal gland
o Adenoma 40%
o Idiopathic 60%
Secondary
o Stimulation is
extraadrenal

Increased hair on face, chin,

chest, abd
Acne
Alopecia
Anovulation/ infertility,
amenorrhea
Decrease in breast size/ adipose
tissue
Increase muscle mass
Male pattern baldness,
deepening of voice, enlarged
clitoris

Increased serum testosterone,

DHEA, DHEAS
Pelvic sonogram r/o
PCOS/ ovarian tumor
CT of drenal r/o
adrenal mass
FSH: LH ratio > 2 (high in
PCOS)
17 hydroxyprogesterone
r/o CAH
24 hour urine for free
cortisol r/o
Cushings syndrome

Primary
o HTN (>140/90)
o Hypokalemia
o Fatigue, weakness
o HA
o Polydipsia/ polyuria
o Facial flushing

PRIMARY
EKG LVH due to
uncontrolled BP
High plasma aldosterone &
low plasmia renin activity
Persistent hypokalemia
HTN w/o edema

tx underlying cause
oophorectomy (for ovarian
tumor)
spironolactone/ vanique
cream (for hirsutism)
finasteride
OCPs
Metformin (PCOS)
Clomiphene (infertility)
Laser therapy, waxing,
bleaching excess hair

Adrenolectomy (unilateral)
if adenoma found
Spironolactone (treatment
of choice) = correct
hypokalemia/ control BP
prior to surgery
Cure rate is > 70%

Aldosterone renin ratio

>30 in upright position =
diagnostic of primary
CT of abd/ pelvic check
for adrenal mass
Adrenal vein sampling =
GOLD STANDARDto dx
usually performed if CT neg
SECONDARY
High PRA

Pheochromocytomas
= Adrenal Tumor

Rare produces/
secretes
catecholamines
Female = males
All ages (mostly in
youngmid adult life)

Mechanism unknown
10% hereditary
usually tumor located in
adrenals
associated w/ vonhippelLindau (VHL) syndrome,
multiple endocrine Neoplasia
type 2 (MEN2),
neurofibromatosis type 1

triad= palpitation, HA, episodic

diaphoresis
RULE OF 10 10% not
associated w/ HTN, 10% extraadrenal, 10% occur in children,
10% involves both adrenals,
10% have mets disease
Paroxysmal sx which may last
minutes to hour
adrenal rush fight/flight
response
tremors, anxiety, paresthesia
abd pain & vomiting, secondary
to ischemic enterocolitis

Adrenal mass discovered

incidentally

congenital defect on pituitary

development, empty sella,
encephalocele,
panhypopituitarism, genetic
abnormalities
Achrondoplasia
Craniopharyngioma

Adrenal Incidentalomas

Asymptomatic

HTN > 140/90

LVH w/ dilated
cardiomyopathy
Facial flushing
EKG = sinus tachycardia
plasma catecholamines &
metanephrines
24 hour urine collection for
catecholamines,
metanephrines,
vanillylmandelic acid
(VMA)
serum chromagranin A
(CgA) = elevated normal =
low @ 8 am/ high in
afternoon & 11 pm
CT/ MRI abd/ pelvic r/o
adrenal mass
MIBG I131 or I123 scan
useful to determine if mass is
pheo or exraadrenal mass

Focused work up needed

tx based on cause
if no surgery warranted
monitor w/ CT scan q 612
months x 5 years

Consult w/ peds/ adult

endo & neurosurgeon
Surgical resection of
pituitary tumors
GH recombinant
replacement therapy (SQ

Laparoscopic
adrenalectomy
Oral antihypertensive
started1014 days before
surgery
o CCB preferred
o Phenoxybenzamine
(C/I in pregnancy)
o ACE (2ndline/ comb
w/ previous) or BB
Lifetime surveillance
required
o Recheck plasma
metanephrines 2 wks
post up/ then yearly
for 10 years
o Monitor BP

ANTERIOR PITUITARY
DISEASE

CAUSE

Growth Hormone
Deficiency

1 in 4,000

SIGNS/SYMPTOMS

Children growth failure,

short stature, low growth
velocity for age, pubertal
stage
Adults non specific sx =
fatigue, dec strength/ exercise
intolerance, increase wt/

LAB/DX

Low GH/ IGF1

GH stimulation test (4 types,
must do 2 to confirm dx)
Xray to assess bone age in
children
DEXA scan for osteoporosis

TREATMENT

~600 adults dx each

year
M>F

Cranial radiation
Sarcoidosis
Larons syndrome
Tumor, surgery
head trauma

difficulty losing wt, anxiety,

social isolation, dec libido,
impaired sleep
Some are asymptomatic

EKG to look for reduced EF at

rest/ exercise
MRI (or CT) of pituitary to r/o
tumor

weekly): Humatropin,
Genetropin

Close monitor by endo,

assess ht/ wt/ growth
velocity

Increased CV mortality/
metabolic syndrome
cardiac/ lipid monitoring

THYROID DISORDERS
Anatomy & Histology of Thyroid Gland

Control of Thyroid Fxn

Fxn of Thyroid Hormone

Located in neck: 2 lateral lobes connected by thin isthmus

Size: 1020 g in normal adults
Rich in blood supply
4 PTH glands that lie behind & recurrent laryngeal nerve
develops during 3rdweek of gestations & hormone synthesis beings at ~11 wks of
gestation
o hormone promotes growth, development, regulates # of homestatic fxn (energy
& heat)
produces T3/ T4
contains 5965% of element iodine
o cretinism severe mental retardation that occurs in children who live in
iodinedef regions that are left untreated during early childhood
Hypothalamic pituitarythyroid axis
o Hypothalamus = command center for endocrine system receives input from
cerebral cortex, from environment (EX = increased cortisol at night) & FB from
organ it controls

Releases TRH(thyrotopin releasing hormone) which regulates pituitary

TSHsecretion
o Anterior pituitary releases TSH(thyroid stimulating hormone or thyrotopin)
in response to TRH
o Thyroid gland releases T 3/T4in response to TSH

T3 is more potent/ active hormone, T4 must be converted to T3 in

periphery
(+) FB = low levels of T3/T4 is sensed by hypothalamus increased secretion of
TRH from hypothalamus
() FB = increased levels of T3/T4 inhibit secretion of TRH form hypothalamus &
TSH from anterior pituitary
Increased metabolism of all body tissues (excluding retina, spleen, testes, lung)
increased rate of use of glucose, fat, protein
o High cholesterol in hypothyroidism/ low cholesterol in hyperthyroidism
Increase in O2 consumption increased vasodilation changes in skin temp, HR,
BP
Increase GI motility/ production of GI secretion diarrhea

THYROID FXN TESTS

THYROID FXN TESTS

Tremors
BEST THYROID FXN SCREENING TEST
Clinical uses = Initial test for suspected thyroid ds, follow pts on hormones, used w/ T4 to
manage pts w/ graves
HIGHincreased dose of levothyroxing
LOW decreased levothyroxin
METABOLICALLY ACTIVE HORMONE
Ordered when TSH is abn to determine the thyroid hyper or hypo fxn
Used to dx Hashimotosin hypothyroidism or autoimmune thyroiditis

Specific for Graves dsin hyperthyroid

Used to dx hyperthyroidwhen T SH is low & T4 is still normal

Used in thyroid ds when pt has protein abnormalities

TSH

Free T4 (FT4)
Antithyroid
peroxidase Ab
Anti
thyroglobulin Ab
Thyroid
Stimulating Ab
T3
FTI

DISEASE

CAUSE

Hypothyroidism
Slowing down of
metabolic processes
23% prevalence
mean age = 50
10:1 F to M ratio
PRIMARY= thyroid
failure
SECONDARY=
pituitary TSH deficiency
TERTIARY=
hypothalamic deficiency
of TRH

Myxedema Coma

End stage of untreated

hypothyroidism

SIGNS/SYMPTOMS

In US
Hasimotos
thyroiditis
Worldwide
Iodine Deficiency
Drugs that block thyroid
hormone synthesis (lithium,
amiodarone, PTU, interferon)
RAI therapy iatrogenic
34 months after tx
Totally thyroidectomy
Excessive iodine intake
Neck radiation
Postpartum thyroiditis
Sub acute thyroiditis
Congenital

Precipitated by sepsis,
cardiac ds, respiratory
distress, CNS ds, cold
exposure, drug use,
noncompliance w/ tx

LAB/DX

Fatigue
Cold intolerance
Dry skin, brittle nails, hair
loss
Weight gain
Weakness
Hoarse voice
Joint aches
Constipation
Puffy face/ hands non pitting
edema
Menstrual irregularities
(amenorrhea/
oligomenorrhea)
Decrease libido/ infertility
Depression, impaired
memory/ concentration

AMS = hallmark
Progressive weakness
Stupor
Hypothermia
Hypoventilation
Shock
Death

On PE delayed reflexes,
bradycardia, coarse hair,
periorbital swelling, CTS,
Goiter
Primary
o Labs = high TSH/ low
Free T4, T3 variable
Secondary
o TSH normal/ low, free
T4 low, TRH high
Tertiary all three are low
(+) thyroid peroxidase Ab +/
thyroglobulin Ab
Hashimotos
Hypercholesterolemia

TREATMENT

Markedly elevated TSH &

FT4/Te
Hypoglycemia
Hyponatremia

Start tx if TSH >10, TSH>5

+ (+) TPO Ab, or TSH > 2.5
Levothyroxine (LT4)
gold standard/ standard of
care
o Once daily, in AM on
empty stomach & wait
12 hrs before eating/
taking other meds
o Start dose = 1.1.6
mcg/kg in adults
o Elderly = start w/ low
dose if CV risk present
Recheck TSH in 46 wks &
adjust dose appropriately
Side effects of med= allergy
to coloring dye, overdosing
hyperthyroidism
arrhythmia (afib),
osteoporosis
Cytomel (synthetic T3)
Armour
Thyroid
ACUTE
MEDICAL
EMERGENCY
Tx in ICU
LT4 IV, warm blankets, lyte
replacement

Hypothyroidism in
Pregnancy

HYPERTHYROIDISM

o
o

DISEASE
Graves Disease

F>M
Mean age = 2040 y/o
M/C/C primary
hyperthyroidism

High mortality in elderly w/

underlying pulmonary/ CV
ds

Antithyroid drug therapy

o PTU/ Methimazole
o +/ propranolol to
control tachy/ HTN
SubTotal Thyroidectomy
o Pretreat pt w/ antithyroid meds until
euthyroid to avoid
thyrotoxic crisis
o Thyroid
supplementaiotn
following w/ LT4
Radioactive Iodine
Therapy (RAI) I 131
causes progressive
destruction thyroid
o Pretreat pt w/
methimazole & d/c 35
days prior
o C/I in pregnancy/
breastfeeding
o Repeat 2nddose in 6
months if needed

Fetla thyroid develop at 1113 wks gestation

1sttrimester TSH = 12,5, 2ndtrimester = 0.2 3.0, 3rdtrimester = 0.33.0
check labs TSH, free T4, Free T3, TPO AB, thyroglobulin AB to r/o hypothyroidism
TX = Levothyroxine
Check TSH every 4 wks during first half of pregnancy
If planning pregnancy need to adjust LT4 w/ a TSH <2.5
If pt becomes pregnant increase LT4 by 2530% as soon as they miss a period/ have (+) pregnancy test
Fetal risks if untreated = premature birth, low birthweight, miscarriage, low IQ babies
Hyperactivity of thyroid gland (excess thyroid fxn)
CAUSES
Graves ds (diffuse toxic goiter)= M/C o
Toxic adenoma (Plummers disease) o
Toxic multinodular goiter
Sub acute Thyroiditis
Primary Increased T4/T3, decreased TSH/TRH
Secondary increased T4/T3, TSH, decreased TRH
Tertiary increased T4/T3, TSH, TRH

CAUSE

Cause unknown
Thought to be autoimmune
o Tlymphocytes become
sensitized to Ag w/in the
thyroid gland &
stimulate Blymphocytes
to synthesize Ab to these
Ag
Stress is thought to be a
trigger
15% have strong familial
predisposition

SIGNS/SYMPTOMS

Hyperactivity, irritability
Heat intolerance/ sweating
Palpitations
Fatigue
Wt loss w/ increase appetite
Diarrhea
Insomnia
Oligomenorrhea/ loss of
libido
Tachycardia/ Afib
Tremors
Goiter
Warm, moist skin
Muscle weakness
Lid lag
Eyes bulging outwards
Graves Ophthalmopathy
sensation of grittiness, eye
discomfort, excessive
tearing, diplopia possible
o Tx= refer to endo,
artificial tear drops,
subtotal

LAB/DX

Elevated FT4
Elevated T3/T4
Suppressed/ low TSH
Elevated thyroid uptake
scanshows hyperactivity
TPO AB might be elevated
Elevated TSHreceptor Ab &
TSI = specific
MRI/ CT of head/ neck
check for ophthalmic
involvement

TREATMENT

Thyrotoxic Crisis
Thyroid storm

Acute exacerbation of all sx

of thyrotoxicosis
May be life threatening

Precipitating Factors:
Stressful acute illness
Thyroid surgery
Infection
Childbirth
trauma

Fever/ flushing/ sweating

Marked tachy (afib)
Agitation/ restlessness/
delirium
N/V/D
Jaundice

Subacute Thyroiditis

thyroidectomy/RAI if
severe
Graves Dermopathy
thyroid acropathy (form of
clubbing), preitibial
myxedema

Acute inflammation of the

thyroid
Age 3050
M/C women

Most likely due to viral

infection mumps,
coxsackie virus, influenza,
adenovirus

Fever
Sore throat
Enlarged thyroid w/ neck
soreness
Initial sx of hyperthyroidism:
palpitation, sweating,
agitation
3 phases: hyperthyroid,
hypothyroid, recovery

Labs usually consistent w/

hyperthyroidism (& only
useful if not previously dx)
o Elevated T3/T4 & FT4,
dec TSH
CBC might show mild
leukocytosis w/ left shift
Non specific LFT abn
Possible hypercalcemia

On PE = exquisitely tender
thyroid gland
High T4& T3
Low TSH
Low thyroid uptake scan
Elevated ESR >100

Some pts will spontaneous

relapse
Rare to fluctuate btwn
hypo/hyperthyroidism due to
changes in fxn of activity of
TSHR AB
High mortality/ 20% enter
coma
PTU in large dose (PO/
NGT)
Potassium iodine
IV corticosteroids
Propranolol IV/ PO to
control tachy
Cooling blanket/
acetaminophen to control
fever
Acetaminophen
Prednisone
Monitor TSH/ Free T4 q 24
wks
Sx usually improve
spontaneously
LT4 if become hypothyroid

OTHER FORMS OF THYROIDITIS

o Hashimotos thyroiditis(chronic autoimmune): (+) thyroglobulin AB, (+) TPO AB & can progress to hypothyroidism

Associated w/ virtiligo, RA, Addisons ds, DM type 1, hypoparathyroidism, pernicious anemia

o Silent Thyroiditis/ Postpartum thyroiditis:5% of women 36 months postpartum
o Drug induced:IFN alpha, interleukin 2, amiodarone
o Acute thyroiditis:due to acute bacteria/ fungal infection & radioactive thyroiditis after RAI I131 tx

Sick Euthyroid Syndrome

Acute & severe illness can

cause abnormalities in TSH/
thyroid hormone levels, in
the absence of underlying
thyroid disease
Major cause = release of
cytokines
Severe illness, caloric
deprivation, major surgery

Consider in pts w/ low T4 &

low FT4 w/o thyroid ds
Free T3 is low = LOW T3
SYNDROME

Tx controversial
Observation unless there is
historic/ clinical evidence
suggestive of hypothyroidism

Thyroid Nodules

Present in 47% of adults in

US
4:1 F:M
thyroid CA rare

THYROID CA

DISEASE

Chronic thyroiditis:
Hasimotos
Dominant portion of MNG
Thyroid, parathyroid,
thyroglossal cyst
Agenesis of thyroid lobe
usually left
Postsurgical reminiance
hyperplasia/ scarring
Post RAI hyperplasia
Benign adenoma (Hurthle
cells)

Papillary Throid CA (PTC)

M/C

Thyroid sonogram
distinguish btwn cyst vs.
solid
Radionuclide scan
identify hot vs cold
o Hot= absorb iodine/
non cancerous
o Cold= non fxn (no
absorption) 5% CA
Needle bx/ FNA for nodules
> 10 mm

PTC= 7090% of all thyroid

CA

SIGNS/SYMPTOMS

FTC = mets common to neck

nodes, bone, lung

PTC thyroglobulin (used as

marker for recurrence/ mets)

Results of bx/ FNA depict tx:

o Malignant = refer to
surgery
o Unsatisfactory FNA =
repeat bx
o Benign = monitor w/
thyroid US
o Follicular neoplasm =
radioanuclide scan to
check hot vs. cold
Benign nodules may regress
spontaneously

TREATMENT

Undifferentiated
(anaplastic) carcinoma

LAB/DX

Follicular Thyroid CA
(FTC)

Medullary Thyroid CA
(MTC)

Exposure to neck/ head radiation

Fhx of medullary thyroid CA
Children, young, adults, male
RF: hx of head/neck radiation, <20/ > 70 y/o, male, increased nodule size (>4cm), new/ enlarged neck mass, vocal cord paralysis, iodine
deficiency, fhx of MEN2/ thyroid CA
c/o hoarseness/ dysphagia, exposure of head/ neck radiation, fhx of medullary thyroid CA, children, young adults, males suggestive

CAUSE

95% present as thyroid lump/

nodule
most benign / asymptomatic

Not associated w/ radiation

exposure
Disease of parafollicular
ccells production of
calcitonin
More aggressive than PTC/
FTC
Extends to cervical lymph
nodes early & distance mets
later (bone, brain, liver,
adrenal medulla)
Familial can be associated
w/ MEN 2 A & MEN 2B

Flushing
Diarrhea
Fatigue
Cushings syndrome

Older pts
Least common

s/sx of pressure/ invasion =

recurrent laryngeal nerve
palsy (hoarseness)

MRI of neck to r/o mets

Total/ near total

thyroidectomy
High risk pts RAI of
residual thyroid remnant
LT4 replacement w/ TSH
btwn 0.10.5
F/U whole body scan,
monitor thyroglobulin Ab q 6
months initially then yearly
for recurrence/ mets
Total thyroidectomy
(RAI & chemo not effective)
calcitonin levels used to
monitor if residual disease is
present after tx of detection
of recurrence

Very resistant to therapy

MOST AGGRESSIVE
rapid growth w/ compressive
sx

Poor prognosis/ death

anticipated w/in 612 months
of dx
Total thyroidectomy

DISEASES OF PARATHYROIDS

Calcium

Parathyroid Hormone

Vitamin D

Calcitonin

DISEASE
Hypercalcemia

CAUSE

Results from excessive Ca2+

finlux into ECF
Hyperparathyroidism/
malignancy = 90%
o Malignancy = M/C/C in
hospitalized pts
o Occurs w/ far
advancement
Various vit d related
problems
Disorders associated w/ rapid
bone turnover
Thiazides
Renal failure
Familial causes (rare)

Critical to our survival important role intracellular/ extracellular metabolism

Serum total Ca = ~9.5 (4.5 is bound to serum protein, 0.5 circulated as insoluble
complexes, 4.5 circulates as free/unbound/ionized calcium)
Total serum Ca2+ can change w/o a change in ionized Ca2+ serum must be
adjusted for abnormal albumin levels
ALWAYS CORRECT FOR ALBUMIN
Regulated by Intestine, Kidney, Skeleton & PTH, calcitriol, calcitonin
Produced by 4 parathyroid glands (behind both thyroid glands)
Serum ionized Ca2+ concentration is continuously monitored by PTH glands
Targets Kidneys inhibits renal Ca2+ excretion, phosphate/ bicarb reabsorption,
PCT production of active vitamin D
Targets skeleton immediately mobilizes Ca2+ from skeleton via activation of
osteoclasts (overtime osteoblasts stimulated)
Targets gut increasing intestinal absorption of Ca2+ through its ability to inc renal
synthesis of vitamin D
Inactive form is made to active form (calcitriol) in kidney
Regulated by PTH increases in PTH stimulate calcitriol production
Primary action of calcitriol = regulate intestinal Ca2+ absroption
Produced by thyroid gland in response to hypercalcemia
Directly inhibits osteoclast fxn
Overall not important to human phys

SIGNS/SYMPTOMS

Usually asymptomatic unless

severe CNS, renal, GI,
cardiac

**stones, bones, abd moans, &

psychic groans**
Stones = renal, polyuria,
polydipsia, uremia
Abd gorans =
constipation,
indigestion, peptic ulcer,
pancreatitis
Bones = osteitis, bone
pain, fx
Psychic moans =
lethargy, fatigue,
depression

LAB/DX

Usually found on routine labs

Next look at PTH level

TREATMENT

Initial tx may be started w/o

specific dx
GOALS correct
dehydration (fluds), enhance
renal calcium excretion,
inhibit accelerated bone
resorption
Tx underlying disorder
parathyroidectomy, low
Ca2+, d/c certain meds,
chemotherapy, tx of sarcoid,
avoid vit d, bisphosphates

Hyperparathyroidism

Age at dx = 5256 y/o

3:1 F:M ratio
21 in 100,000

primary
o 85% from single
parathyroid adenoma
() FB on parathyroid is
lost
o 15% from multiple
gland hyperplasia
increase in cells
o <1% from parathyroid
carcinoma
secondary initiated by
another organ (M/C kidney)
Tertiary bone disease

Asymptomatic
Possible non specific sxs

Often discovered incidentally

on labs w/ hypercalecemia
noted
PE noncontributory
Labs total/ ionized Ca2+,
albumin levels, PTH
Imaging studies used to
guide surgeon once surgical
therapy decided
o Sestamibi scan
o U/S of neck
o CT/MRI

renal ds reduced
circulating vit d levels due to
decreased nephron mass

most will have osteitis

fibrosa

decreased vitamin d/
hypocalcemia
persistent
hyperparathyroidism

deficient PTH activity which

causes dec ionized Ca2+
M/C/C = thyroidectomy
Autoimmune
Congenital
Metal overload

Increased neuromuscular
excitability
Chvosteks sign twitching
of upper lip after tapping on
facial nerve below zygomatic
arch
Trousseaus signcarpal
spasm after inflating a cuff
on upper arm above SBP for
23 min

Hypocalcemia
Labs PTH, vit D, calcium,
magnesium, phosphorus

Renal Osteodystrophy

affects 90% of dialysis pts

Hypoparathyroidism

PITUITARY ADENOMAS

Primary
o Mild = observe
o Parathyroidectomy for
sx/ severe
Secondary
o Medical management
o Correct vit d deficiency
For underlying CKD
reduce PTH levels = dietary
phosphate restriction,
phosphate binders, calcium
supplementation limited,
calcitriol
Indications for surgery=
bone pain/ fx, pruritus,
calciphylaxis, extraskeletal
nonvascular calcifications,
elevated PTH despite med
therapy, refractory
hypercalcemia/
hyperphosphatemia
f/u calcium labs x several
months after surgery
calcitriol 0.51 mcg daily
calcium carbonate
supplementation 13 grams
daily
phosphate restriction
Calcium + vit d
supplementation/ diet rich in
calcium containing foods
Parathyroidectomy/ perform
auto transplantation
Treat underlying cause if
possible
Necessary to wear bracelet
that ID them as having
disorder

NonFunctional Adenoma= 10% of all pituitary adenomas

o Can be w/ or w/o sx, but all labs are normal
o If no sx = monitor q 612 months & repeat MRI yearly
Microadenomas = < 1 cm
Macroadenomas = > 1 cm
Clinical manifestations= temporal field defects (unilateral/ bilateral), decrease visual activity, diplopia, ptosis, HA
Labs= Prolactin, GH, IGF1, AM cortisol, ACTH, 24 hr urine for free cortisol, FSH,LH,TSH, FT4, testosterone

DISEASE

CAUSE

Pregnancy/ lactation

SIGNS/SYMPTOMS

Prolactenoma

Prolactin hypersecretion
M/C/C of microadenomas in
brain
F>M
85% have long term
remission, 15% have
recurrence

Women= amenorrhea/
oligomenorrhea,
galactorrhea, infertility, dec
libido, wt gain, mild
hirsutism
Men= dec libido, low
testosterone, impotence,
infertility, dec muscle mass,
visual changes,
gynecomastia, dec energy,
osteoporos

** Prolactinmaintains
lactation, decreases reproduction
fxn, suppresses sexual drive

Somatotropinoma
(GH Secreting Adenomas)

Leads to excessive IGF1

2ndM/C pituitary tumor
Mean age 4050 y/o
M=F
Uncommon
15%

almost always due to

pituitary adenoma
40% due to mutation of alpha
subunit of stimulatory
guanosine triphosphate
binding protein
Gigantism prepubescent
adolescent before fusion of
epiphyses of long bones
Acromegaly(adults only)

Extremity enlargement,
hands bulky w/ moist
handshake, prominent
mandible
Carpal tunnel syndrome
Arthralgia/ degenerative
arthritis
Hypertrophic
cardiomyopathy
Glucose intolerance/
hyperinsulinema
HA, visual loss (bitemporal
hemianopsia)
Dec libido, impotence,
irregular menses, amenorrhea
Obstructive sleep apnea
Sx develop insidiously
~510 yrs

LAB/DX

TREATMENT

Visual exam/ visual fields by

confrontation
Breast exam glactorrhea/
gynecomastia
Beta hCG r/o pregnancy
Prolactin (PRL) > 100
ng/mL(normal is <20
ng/mL)
Labs= PRL, TSH,
testosterone, LH/FSH, LFT,
BUN/ Cr
MRIof pituitary w/ & w/o
contrast confirm dx

Elevated GH/ IGF1

elevated(best test)
o Not dx b/c of episodic
secretion & short life
Abnormal 2 hr GTT
High serum insulin
Glucose Suppression test
most specific
o GH > 2ng/mL =
diagnostic (in healthy
pts GH is suppressed
below 2)
MRI of pituitary r/o tumor

Cushings Disease

Benign microadenomas (<10

mm or 1 cm)

Insidious onset
Central obesity
Moon faces

AM cortisol/ ACTH
24 hr urine collection for
free cortisolhigh

Long life management/ f/u

Dopamine Agonists
o Cabergoline
o
Bromocriptine
(FIRST LINE)
Repeat PRL x 1 month after
med initiation & MRI in 612
months
Transsphenoidal pituitary
adenomectomy 2ndline/ pts
intolerable to meds, mass too
large
Radiation therapy 3rdline
Transsphenodial
microsurgery = FIRST
LINE
Dopamine antagomist
cabergoline/ bromocriptine
Somatostatin analogs
(Ocetreotide LAR/
Lanreotide)
Radiation 3rdline need to
be followed q 6 months for
GH/ another anterior
pituitary fxn
Recheck GH/ IGF1 levels
46 wks after surgery (add
drug if still high)
o GH < 2 f/u GH &
IGF1 q 6 months to 2
yrs q yearly
At risk fro colon CA early
colonoscopy
Transsphenoidal resection
of pituitary adenoma
FIRST LINE

More common in F
Onset age = 2040
Accounts for 70% of
cushings syndrome

Excess ACTH by tumor from

anterior pituitary tumor

Plethora
Thin extremeties
Easy bruising/ purple striae/
hyperpigmentation
Acne, hirsutism
Supraclavicular fat pads
Myopathy
HTN, IGT, depression

rare

Thyrotropin Secreting
Pituitary Adenoma

Gonadotropin Secreting
Pituitary adenomas

Androgen Secreting
Tumors
(Ovaries or adrenal)

Very rare

Adrenal cause of amenorrhea

Sx of hyperthyroidism w/
goiter
DOES NOT have systemic
manifestaitons of Graves ds
(ophthalmopathy or
dermopathy)
Visual changes (w/ large)
Sx of hypogonadism

Wt loss
Anorexia
Bloating
Back pain

o > 125 mg/dL in 24 hr

diagnoistic
Low doseover night 1 mg
dexamethasone suppression
test > 5 ng/mL is diagnostic
Highdose dexamethasone
suppression test
o Differentiate btwn
cushings ds & ectopic
ACTH or adrenal tumor
o > 50% = pituitary (need
MRI)
o <50% = ectopic ACTH
(CT chest/ abd rec)
Midnight salivary cortisol
test
MRI of pituitary to r/o
pituitary adenoma

High TSH, FT4, FT3

MRI to look for tumor

Transsphenoidal Surgery
Somatostatin agonist
normalize TSH/ FT4
Radiation therapy
Radioactive iodone therapy
or thyroidectomy
Surgery
Radiation (if needed)

Surgical resection

Desmopressin (synthetic
vasopressin)
Monitor q 612 months
Pt edu avoid dehydration/
water intoxication

Increased FSH & normal/

high LH
Increased alpha subunit
Elevated serum estradiol
High testosterone > 200
ng/dL & DHEAS > 700
ng/dL
Ct scan to confirm dx

Radiation Therapy
o Pt w/ persistent/
recurrent after surgery
Ketaconazole or Metyropone
o Block adrenal steroid
synthesis
o Used if surgery is not an
option

DIABETES INSIPIDUS (DI)

excretion of tasteless urine

Inability of kidneys to produce concentrated urine b/c lack of hormone vasopressin/ lack of response to hormone
Deficient ADH action passage of large amounts of very diluted water
Two kinds: C entral/ Neurologic & Nephrogenic

DISEASE
Central/ Neurologic DI

Failure of pituitary to secrete

ADH

CAUSE

Autoimmune
Hypophysectomy
Surgery
Idiopathic
Familial
Tumors/ cysts

SIGNS/SYMPTOMS

polyuria, polydipsia, nocturia

colorless urine, dehydration
infants irritability, crying,
growth retardation,
hyperthermia, wt loss

LAB/DX

History water drinking

patterns, urinary behavior,
family hx
Exam is usually normal
Labs CMP, UA, urine
sodium, serum/ urine

TREATMENT

Nephrogenic DI

kidneys failure to response to

circulating ADH

Interruption to blood supply

from head trauma
3rdtrimester pregnancy
chronic renal disease
hypokalemia
hypercalcemia
protein starvation
sickle cell
Sjogren
Lithium toxicity
Other meds
Congenital defect

METABOLIC BONE DISEASE

Osteoblasts

Fxn of bone

DISEASE

CAUSE

Osteoporosis

silent thief
skeletal disorder
characterized by
compromised bone strength,
predisposing to inc risk of fx
M/C metabolic bone ds in US
Primary= reduced bone
mass/ fx in postmenopausal

osmolality (SG < 1.005,

urine osmolality < 300)
Water Deprivation Test
Vasopressin Test
MRI of pituitary w/ & w/o
contrast r/o tumors

Tx underlying cause if
possible
Diuretic/ salt restriction
Monitor q 612 months
Pt edu avoid dehydration/
water intoxication

Located on surface of bone/ osteoid

Synthesize/ secrete components of bone matrix
Can give rise to osteocyteswhen cell is encased by osteoid matrix that
it synthesizes itself
o Actively involved w/ maintenance of bony matrix
Responsible for bone resorption
o Lie in resorption craters (Howship lacunae) on
bone surfaces/ in deep cavities (cutting cones)
o Secrete protons, proteases, proteoglycandigesting
enzymes acid hydroxyapatite crystals releasing Ca2+
Derived from macrophages

Osteoclasts

children enuresis,
anorexia, linear growth
defect
high volume of daily urine

M/C/C = aging, high dose

corticosteroid admin,
alcoholism, smoking, sex
hormone deficiency
RF:white, female, early
menopause/ late menarche,
amenorrhea, postmenopausal
state, thin build/ small
stature, smoker, ETOH,
immobility, family hx, use of
systemic steroids, heparin,

Provides rigid support to extremities & protects vital organs

Assure normal locomotion & strong site attachments for muscle
Provide large reservoir of ions such as Ca2+, Mg+, Phosphorus
Houses hematopoietic elements

SIGNS/SYMPTOMS

LAB/DX

Usually asymptomatic until

fractures occur
Loss of height

Osteonecrosis of the jaw

possible complication of
bisphosphate usage

PE low body wt (BMI

<19) + signs
Labs calcium, phosphate
PTH normal alk phos
normal unless fx
xray
DXA scandetermines bone
density of lumbar spine/ hip
o Est/ confirm dx, predict
future fx risk, assess
changes in bone mass

TREATMENT

Prevention= adequate
Ca2+/ vitamin D intake,
exercise, tobacco use, ID/ tx
alcoholism, d/c steroids asap
or use at minimal dose
Estrogen Treatment used
for prevention available
PO/transdermal
Weight bearing exercise
Endocrine consult
Vertebroplasty/ kyphoplasty

or older men/ women

(Senile)
Secondary= bone loss
resulting form specific
disorder (hyperthyroidism,
immobilizaitons,
hypervitaminosis A)

thyroxine, anticonvulsants,
chemo, lithium

Measure in women > 65,

men > 70, F/M 5070
w/ known RF
o T 1 to 2.4 = osteopenia
o
T < 2.5 =
osteoporosis o
T<2.5 + fx = severe
** repeated q 23 years w/
normal levels, or 12 yrs in
those undergoing tx

Pagets Disease

2ndM/C bone ds
focal disorder of bone
remodeling characterized by:
o accelerated rate
bone turnover
o disruption of normal
architecture of bone
o gross deformity of
bones
unusual < 40 y/o
rare < 25 y/o
M:F = 3:2 ratio

Vitamin D Deficiency

Absorbed via diet/ sun

liver kidney to become
active vitamin D
Fxn increase Ca2+
absorption in SI/ kidney,
insulin secretion,
immunomodulation, bone
resorption/ remodeling

chronic slow viral infection

of bone
paramyxovirus/ measles
familial clusters of disease

Inadequate sun exposure

Poor vitamin d intake
Malabsorption
Darker skin interferes w/
cutaneous synthesis
Synthesis in skin declines w/
age
Medications
(anticonvulsants,
glucocorticoids)

asymptomatic 7090%
bone pain = M/C compliant if
they do complain
skeletal deformity
fx
hat size increases
bones near to surface may
feel hot
complications
o CNS: compression of
nerves, deafness, HA
o Rheum: OA, gout
o Cardiac: CHF
o Metabolic:
hyperuricemia, gout
o Neoplastic:
osteosarcoma,
fibrosarcoma,
chondrosarcoma
Often silent
Children = bowing of legs
Adults = chronic muscle
aches/ pains

increase alk phos level

bone turnover
incidental finding on routine
xray
o pelvis, femur, skull,
vertebrae = M/C
involved

Low vitamin D levels (25

OH)D
Elevated PTH levels

Meds for bone formation

vitamin D, bisphosphates,
PTH
Meds to reduce resorption
bisphophates, SERM
(raloxifene), calcitonin,
Forteo
Prognosis= good if detected
early fx may lead to chronic
pain, disability, death
pt eduprevention, RF,
DXA scan, benefits of
exercise, no smoking, limit
EToh
GOALS relieve sx/
prevent complications
Physical therapy
Bisphosphates
Acetaminophen/ NSAIDs
Calcitonin (only if
bisphophates C/I)

Various methods
No standard tx regimen
exists
Ergocalciferol (vitamin d2)
= most widely used form of
vitamin d
o Stimulates calcium/
phosphate absorption
from SI

(activates osteoclasts &

induction of osteoblasts)

Rickets

Minimal amts of vit d in

human breast milk

Occurs in children w/ open

growth plates
Vitamin d deficiency
M/C/C
Hereditary= x linked
hypophosphatemia
Lack of sun exposure
Occurs in adults w/ closed
epiphyses
Lack of sun exposure
Lack of vitamin D intake
Certain surgeries
Celiac sprue
Chronic pancreatitis

Osteomalacia

Bulbous knobby
deformities of knees, ankles,
costochondral jxn (rachitic
rosary)
Dental abnormalities
Impaired/ poor linear growth
fractures

Bone pain
Muscle weakness
Loosers zones/ Milkmans
pseudofractures

o Promotes calcium
release form bone into
blood
prevention
o breast feeding
vitamin d supplementation

Prevention
o Inadequate sun
exposure/ aging,
pregnant, lactating =
8001000 IU daily + sun
o Malabsorption = 50000
IU vit D2 q weekly
o Interactive meds =
50000 IU vit D2 q 1,2,or
4 weeks
Vitamin d supplementation
+/ UVB radiation (tanning
bed or portable UVB device)
Braces
surgery

REPRODUCTIVE & GONADAL DISORDERS (MALE/FEMALE)

Gonadal Hormone production

Evaluation of Male Gonadal Fxn

Hypothalamus releases GnRH is secreted in pulses q 90120 min stimulates

LH & FSH
o In men LH stimulates testosterone production & FSH
spermatogenesis
Testosterone, DHT, DHEA, estradiol produced by testes
95% of testosterone is produced by leydig cells (the rest is
produced in adrenal/ peripheral tissues)
60% is bound to sex hormone binding globulin (SHBG)
2% is not bound to protein
total testosterone DHT via 5 alpha reductase enzyme
DHT induces formation of prostate & external male
genitalia, pubic hair
o In women LH causes ovulation & FSH stimulates ovarian follicle
maturation
DHT reduces LH pulse frequency
Estradiol reduces LH pulse amplitude
Androgen deficiency during 23 months of fetal development ambiguous
genitalia

Semen Analysis 3 samples over 23 month pd

Check AM total & free testosterone
Sex hormone binding protein/ globulin
Check LH & FSH & Prolactin
** low testosterone w/ low/ normal LH & FSH hypothalamic or pituitary
hypogonadism
** low/ normal testosterone w/ high LH & FSH gonadal failure (primary)
Testosterone Therapy IM testosterone enanthate, androderm patch, testim,
androgel, axiron
o Check CBC, LFT, PSA before starting therapy
o w/o tx until male reaches 13
o C/I w/ prostatic carcinoma
o Adverse rxn: erythrocytosis (polycythemia), gynecomastia, priaprism,
acne, aggressive behavior, worsening sleep apnea, CV risks
o Monitor PSA/ DRE initially & then yearly due to increase risk for
prostate CA
LH cause ovulation & FSH stimulates ovarian follicle maturation
Follicular phaserelease of GnRH stimulates secretion of FSH binds to
ovarian granulosa cells thecal androgen to estrogen conversion & follicular
maturation secretion of estradiol pituitary LH surge
Luteal phaseLH surge release of mature oocyte corpus luteum
secretes progesterone, estradiol, & inhibits androgen suppression of GnRH/
FSH corpus luteum dissolves & menstruation occurs

General labs to evaluate testicular fxn

TX of Hypogonadism

Female Reproductive Endo/ Infertility

DISEASE

CAUSE

Polycystic Ovarian
Syndrome (PCOS)

M/C/C of chronic
anovulation

Leydig cell aplasia= defective development of testicular Leydig cells

caused by mutation of LH receptor
Prepubertal androgen deficiency poor secondary sexual development
o Fail of penis to enlarge, small testes, failure of marked rugae
characteristics of puberty due to failure of scrotum to develop
o Voice remains high pitch, decrease muscle mass, decrease axillary/
pubic hair
o Absent/ sparse facial, chest, upper abd, back hair
Deficiency after puberty dec libido, ED, low energy/ decrease facial & body
hair growth

Accumulation of
incompletely developed
follicles in ovaries due to
anovulation
Associated w/ increased
ovarian androgen production
LH > FSH = testosterone
production
Genetic link

SIGNS/SYMPTOMS

Menstrual abnormalities
oligomenorrhea or
amenorrhea
Hyperandrogenism acne,
hirsutism, male pattern
baldness/alopecia
Infertility
Insulin resistant
Central obesity
Metabolic syndrome
DM type 2

LAB/DX

High total testosterone

High DHEA/DHEAS
High total insulin
Low SHBG
High LH/FSH ratio
US polycystic ovaries

TREATMENT

Life style modifications

appropriate diet/ exercise
COCPS
Spironolactone
Metformin for insulin
resistance
Clomiphene citrate/ low dose
gonadotropins
Complications:infertility,
risk for endometrial CA, risk
for type 2 DM/ gestational

Primary Amenorrhea

Secondary Amenorrhea

Cryptomenorrhea

HYPOTHALAMIC
AMENORRHEA

Functional Hypothalamic
Amenorrhea

Sleep apnea

Gonadal gysgenesis (turners

syndrome)
Hypothalamic pituitary
insufficiency
Androgen insufficiency
Imperforate hymen
Outflow tract disorders
Anorexia
Pregnancy M/C/C
PCOS
Premature ovarian failure
Wt related amenorrhea
Hyperprolactinemia
Exercise related
hypopituitarism

No menses by age 16 but

normal growth/ secondary
sex characteristics OR
No menses & no onset of
puberty by age 14

Outflow obstruction of
menstrual blood flow
Imperforate hymen
Transversevaginal septum w/
functioning uterus
Isolated vaginal agenesis w/
functioning uterus
Isolated cervical agenesis w/
functioning uterus

No menses for more than 3

cycyles in a women who has
previously cyclic menses OR
No menses for 6 months if
previous cycles irregular

Intermittent abd pain

Possible difficulty w/
urination
Possible lower abd swelling
Bulging bluish membrane at
introitus

History
Physical exam
TSV sonogram

GENERAL WORK UP
FIRST R/O PREGNANCY
Progesterone w/draw test
(Provera 10 mg x 510 days)
o (+) = anovulation
o () = estrogen deficiency/
outflow tract abn

inc FSH/ LH =
ovarian failure

low/ normal
FSH/LH = CNS
pituitary dysfxn

now W/D bleeding

w/ E & P test =
outflow tract
infection
Check TSH, FT4
Check LH/FSH
Measure prolactin
o High prolactin, normal
TSH/FT4 = MRI of
brain to r/o pituitary
adenoma
o High/ NL prolactin w/
high TSH/ low FT4=
primary hypo
Check DHEA, DHEAS &
total testosterone
o High = PCOS, androgen
secreting tumor

DM, CV disease,
dyslipidemia, hepatic
steatosis, obstructive sleep
apnea, HTN
Treat medical condition
OCPs
Progesterone alone
REFERALLS ESP > 30
Y/O
Reassurance

Those who desire pregnancy

Bromocriptine
suppress secretions of
prolactin
o Clomid induces
ovulation
o Gonadotropins
FSH/LSH
Surgical intervention needed

Genetic, endocrine, anatomical causes (developmental defects, brain tumors, infiltrative ds I.E = Sarcoidosis, hemochromatosis, lymphoma)
Check serum estradiol or progesterone withdraw test
o (+) = use it q 3 months to avoid endometrial hyperplase
o () = may need HRT
Low/ low normal FSH/ LH
Malnutrition
Reversible
anovulation
Excessive exercise

M/C/C of amenorrhea

Exercise Induced
Amenorrhea

Amenorrhea associated w/
eating disorders

Could be primary or
secondary

PITUITARY
AMENORRHEA

Sheehan Syndrome
(postpartum
hypopituitarism)

OVARIAN
AMENORRHEA

Premature Ovarian Failure

(before age 40)

OTHER CAUSES
AMENORRHEA

Psychological stress
Dysfxnal release of GnRH
women who participate in
competitive sports:
gymnastics, ballet,
marathons, running,
swimming/diving
Anorexia Nervosa mean age
= 1314
Bulimia

TRIAD = eating disorder,

amenorrhea, osteoporosis

Exercise severe
depression of GnRH low
estradiol level

A.N = body wt < 85%

normal age/ ht
Usually normal body wt w/
bulimia

Hypothalamic suppression
severe dec in GnRH low
LH/FSH low estradiol

Psychiatric referral
Need to gain weight

Genetic Causes: GnRH receptor gene mutation LH/FSH def

Endocrine causes:
o hyperprolactemia high PRL suppresses GnRH secretion 50% w/ pituitary tumor
o Craniopharyngioma
Anatomic causes: Autoimmune disease (lymphocytic hypophysitis), pituitary necrosis, heehans syndrome
labs FSH/LH, PRL, TSH,
Pituitary inability to secrete
Inability to breast feed
Replacement of deficient
gonadotropins
hormones
Fatigue
AM cortisol, ACTH,
Watch for minor illnesses
Postpartum pituitary
Wt loss
GH/IGF1
ischemia/ necrosis
can lead to crisis & may
Lack of menstrual bleeding
*** all hormones are low =
Severe HTN
require adjustment of
Loss of pubic hair/ axillary
panhypopituitarism
hormones
hair
CT/ MRI of pituitary r/o
Low BP
tumors
Hypothyroidism
hypocortisolism
**Dx based off clinical evidence
of hypopituitarism w/ hx of
postpartum hemorrhage
Ovarian failure cause by depletion of ovarian follicles
Clinical picture of amenorrhea & FSH > 40 IU/L
Causes: Premature ovarian failure, menopause, autoimmune destruction, iatrogenic ovarian injury causing POF (chemo, radiation, torsion w/
surgery)
Possible genetic
Irregular periods/ skipping
low estradiol < 50 pg/mL
Hormone replacement
Depletion of ovarian follicles
periods, amenorrhea
therapy
FSH > 40
Support
RF: age, family hx
Hot flashes
Complications= infertility,
Night sweats
osteoporosis, psych:
Vaginal dryness
depression/ anxiety
Irritability/ mood swings
Dec libido
Thyroid Disorders Hyper/Hypothyroidism
Outflow Tract Disorders, Ashermans syndrome
o Mullerian agenesis M/C/C of primary amenorrhea normal ovaries & female sexual charactertistics shortened or absent vagina & NO
UTERUS
o androgen insensitivity syndrome (AIS) minimal sexual hair, male karyotype w/ mutation of androgen receptor on x chromosome,
normal testicular development (but not external male sexual structure= female phenotype)

Precocious Puberty

congenital outflow obstruction Transvaginal septum & imperforated hymen, present of cyclic lower abd pain/ amenorrhea, presence
of uterus needs to be surgically corrected
o Ashermans Syndrome intrauterine adhesions (from uterine surgery) menstrual disturbances, infertility, recurrent spontaneous
abortions

Dx via hysteroscopy & () w/draw bleeding w/ estrogen & progesterone test

OBGYN ovulation needed & tx w/ lysis of adhesions & HRT

Post infection (mumps), Post radiation, Post chemo
Contraceptive related
o Post pill amenorrhea failure to resume menstruation w/in 6 months after d/c of OCP due to disruption of hypothalamic pituitary
ovarian mechanism
o Mirena IUD
o Depo Provera amenorrhea after 1styear of use this is reversible
Puberty onset before age 8 in girls/ 9 in boys
Develop tall stature during childhood but become short as adults due to early epiphyseal fusion of long bones
Central/ complete/ true precocious puberty (CPP) early/ premature activation of maturation of hypothalamic GnRH production
o M/C idiopathic
o CNS tumors
Incomplete isosexual precocious puberty/ precocious pseudopuberty/ peripheral precocious (PPP) ectopic gonadotropic secretion
(nonGnRH produced)
o Less common
o Presence of sex steroids is independent of pituitary gonadotropin release & w/o involvement of GnRH

CAUSE

GIRLS
o Follicular cysts
o Granulosa/ theca cell
tumors
o Adrenal rest trissue
o Exogenous estrogen
admin
o Hypothyroidism
o McCuneAlbrigth
Syndrome
BOYS
o Gonadotropin secreting
tumor
o Autonomous androgen
secretion

SIGNS/SYMPTOMS

GIRLS
o Breast/clitoris
enlargement
o pubic/ axillary hair
o menarch 23 yrs after
breast enlargement
o pubertal growth spurt
BOYS
o Testicular enlargement
o Growth of penis/
scrotum
o Appearance of pubic
hair
o Pubertal growth spurt

LAB/DX

Kallmanns Syndrome

1 in 10,000 86,000 ppl

M>F

Congenital
Idiopathic

Decreased sense of smell

Men= decreased libido, ED,
dec muscle strength
Women= amenorrhea

TREATMENT

High early morning

testosterone in boys
High estradiol levels in girls
High DHEA/DHEAS
Low LH/FSH
17OH serum progesterone
r/o CAH
TSH r/o hypothyroidism
Beta hCG
GnRH stimulation test w/
leuprolide (LH/FSH will be
elevated in CPP)
Xray of hand to determine
bone age
MRI of brain r/o pituitary
tumors
Pelvic sonogram, US testes,
CT pituitary r/o tumors

Low GnRH
Low testosterone
Low FSH

CPP
o GnRH analog only tx
(Lupron, Histrelin,
Nafarelin acetate)
PPP(depends on cause)
o Medical
o Surgical
GOAL= suppress episodic
secretion of gonadotropins
Refer to peds endo
f/u q 46 months to ensure
progression of puberty has
been arrested
GnRH agonist can be
stopped once age appropriate
puberty is reached

Klinefelters Syndrome

M/C cause of genetic

hypogonadism
1 in 5000 male births

Normal/ low testosterone

High LH/FSH
High estradiol
Azoospermia
Chromosomal analysis 47,
XXY

low/ normal testosterone

high LH/FSH
46 XY karyotype

testosterone replacement
therapy

Diminished facial/ body hair

Persistent gynecomastia
Small/ firm testes
Insufficient libido/ infertility
Abnmoral skeletal
proportions
Intellectual impairment/
lower IQ
Dyssocial behavior
Inc risk for COPD,
extragonadal germ cell
tumors, CVA, glucose
intolerance, primary
hypothyroidism, breast CA
short statue
webbed neck, hypertolerism,
cubitul valgus, unusual chest
shape (usually sunken chest
pectus excavatum)
congenital cardiac anomalies
cryptorchidism

appear during puberty

small penis
decreased axillary/ pubic hair
empty scrotum

very low testosterone

markedly high LH/FSH
46 XY karyotype on
chromosome analysis

testosterone replacement
therapy
implantation of testicular
prostheses for cosmetic
purposes

testosterone deficiency
during 3rdtrimester of
pregnancy
failure of testes (one or both)
to descent in scrotum
spontaneous descent occurs
during 1styear of life

unable to palpate testis in

scrotal sack
unilateral M/C

found on PE

surgery by age 2
complications inc risk of
inguinal hernia, torsion,
testicular CA, infertility

familiar form of muscular

dystrophy
Type 1 80% affected males
are associated w/ primary
testicular failure

No therapy to prevent
progressive muscular atrophy
Testosterone therapy
indicated only if testosterone
low

One extra X chromosome

mostly XXY
Abnormal development of
seminiferous tubules,
azoospermia, abnormal
leydig cells

Noonans Syndrome

Inherited autosomal
dominant
have mutation in PTPN11
gene on chromosome 12
associated w/ seminiferous
tubular size w/ or w/o
sclerosis, diminished or
absent germ cells & leydig
cell hyperplasia
embryonic development

Bilateral Anorchia
(Vanishing Testes
Syndrome)

1 in 20,000 males
3% of phenotypic boys that
undergo surgery to correct
uni or B/L cryptorchidism
are found to have absence of
1 or both testes

Cryptorchidism

Myotonic Muscular
Dystrophy

Progressive muscle weakness

& atrophy of face, neck,
hands, LE muscles
Testicular atrophy noted in
adult hood

Testosterone replacement
therapy: 200 mg IM q 24
wks
Prognosis
o Pt feel better w/
androgen replacement
o Personality defects do
no improve & they
require long term
psychiatric counseling

Autosomal dominant

Androgen insensitivity

mutation of androgen
receptor
gonadal tumor

Initially testosterone
secretion is normal &
secondary sexual
characteristics develop
After puberty the
seminiferous tubular atrophy
results in dec in testicular
size infertility
completeMale, XY w/ testes,
full breasts but primary
amenorrhea (mix of male/
female characteristics)
incomplete vary isolated
infertility to ambiguous
genitalia & hypospadias

high LH
variable FSH
high testosterone level

peds endo referall

surgery
psychiatric counseling

LIPID DISORDERS

Cholesterol

LDL

HDL

DISEASE
Hyperlipidemia

CAUSE

Hypercholesterolemia

familial (primary) caused by

genetic abnormalties
acquired (secondary) from
DM, alcohol use,
hypothyroidism, obesity,
sedentary lifestyle, renal/liver
ds, drugs (estrogen, thiazides,
BB)
lifestyle
genetic

soft, waxy substance found among lipids in bloodstream

used to form cell membranes + hormones
high levels in blood major risk factor for CHD
bad cholesterol
major cholesterol carrier in blood
high levels slow build up of plaques in the walls of arteries restricted blood
flow MI/ stroke
good cholesterol
carries cholesterol away from arteries & back to liver
may remove excess cholesterol from fatty plaques/ slow their growth
high levels protective
CAUSES OF DECREASED LEVELS:physical inactivity, smoking, DM,
obesity, anabolic steroids, BB, retinoids

SIGNS/SYMPTOMS

LAB/DX

most are asymptomatic

xanthoma usually indicate
genetic cause
o M/C = xanthelasmas =
affecting eyelids in 2/3
tendenous xanthoma
corneal arcus

Premature arcus senilis

Lipemia retinalis cream
colored retinal vessels

evidence of CVD/ CHD risk

equivalent = screened w/
fasting complete lipid profile
those w/o RF = screened w/
total cholesterol

Increased total cholesterol

>240

TREATMENT

USPSTF recommends
screening those w/ no
evidence of CVD at age 35 &
NCEP says 20
Life style modifications =
FIRST LINE
o Reduce total fat intake to
2530% of diet,
saturated fat to 7%,
dietary cholesterol < 200
mg/day, Mediterranean
diet
o 30 mins exercise daily

increase antioxidants via

fruits & veggies inc
fiber
o CAD prophylaxis w/
low dose aspirin
o Smoking cessation
Statins = first line pharm tx
Niacin, bile acid sequestrate,
fibric acid derivatives,
ezetimibe

OBESITY DISORDERS

Obesity

BMI

Waist Circumference (measuring abdominal obesity)

Assessment of Obesity

Thrifty gene hypothesis

Leptin

Ghrelin

DISEASE

CAUSE

Obesity

Small excess caloric intake in

relation to energy

Significant increase above ideal body wt due to accumulation of excess body fat,
adversely affecting life expetancy
Wt in kilograms divided by the ht in meters squared
Wt in pts multiplied by 704, divided by ht in inches squared
Widely used in epidemiologic research & clinical practice to assess adiposity
Normal= 18.524.9
Overweight= 25.0=29.8
Class I Obesity= 30.0 34.9
Class II Obesity= 35.039.9
Class III obesity= > 40
Males= > 40 inches
Women= > 35
Measurement of % fat by DEXA GOLD STANDARD but its expensive/
used primarily in research
Bioimpedance inexpensive & widely used tool useful in following tx
response
CT / MRI measure distribution of body fat subQ vs. intraabd useful in
research
Waist circumference/ skinfold thickness simple assessment tools useful in
assessment of body fat distribution
Constant abundance of food in those w/ genotype efficiently prepares individuals
for a famine that never comes
Mediator of long term regulation of energy balance suppressing food intake
inducing wt loss
In obese high circulating levels BUT they are leptinresistant
Fast acting hormone
Plays role in meal initiation
In obese decreased levels

SIGNS/SYMPTOMS

LAB/DX

Measure BMI
Measure waist circumference

TREATMENT

Initially reduce caloric intake

by 5001000 kcal/day

expenditure over long pd of

time
Genetic factors/
susceptibility genes
Environmental factors fetal
undernutrition, food intake,
physical activity, culture,
medications, classic
endocrinopathy

Portion control, split entre,

set regular times to eat
Limit saturated/ trans fats
Increase daily intake of
fruits/ vegs
Increase fiber
Limit sweetened beverages
drink more water
Physical activity that is
equivalent to weekly
expenditure of 2,500 kcal
Behavioral modification
therapy
Bariatric surgery

DIABETES

RFphysical inactivity, first degree relative w/ DM, high risk race/ ethnicity, women who delivered baby > 9 lbs, HDL < 35, hypertension >140/90, A1c >5.7, conditions
associated w/ insulin resistance (severe obesity, acanthosis nigricans, PCOS), CVD history
TO DIAGNOSE DM:
o A1c > 6.5%, FBG > 126 or 2 hr >200 during OGTT or random PG > 200
Type 2 DM testing all individuals overweight/ obese w/ > 1 DM risk factor, testing starting at 45, if normal results 3 year interval repeat testing
Pre DM testingA1c, FPG, 2 hr PG after 75 g OGTT, identify/ treat other CVD risk factors, consider testing in children/ adolescents who are overwt & have > 2 DM risk
factors
Gestational DMscreen at 2428 wks

DISEASE

CAUSE

Hypoglycemia

Reduction in plasma glucose

concentration to a level that
may induce s/sx

Hypoglycemia w/o DM

Abnormalities in
mechanisms involving
glucose homeostasis
Secondary to endocrine
disorders
Liver malfunction/ renal
failure
GI surgery/ dumping
syndrome
Functional B cell dysfunction
Alcohol related
Drug induced
Adenoma of islets of
langerhans
insulinoma
90% benign
rare
can be associated w/ MEN
type
25% 1of general non obese,
non diabetic population

SIGNS/SYMPTOMS

LAB/DX

TREATMENT

Begin w/ FPG < 60

AMS @ < 50
o Glucose = predominant
metabolic fuel of brain
survival dependent
on cont. supply of
glucose from peripheral
circulation

Depend on suspected cause

Counter regulatory hormones
inc in E/ NE, glucagon,
cortisol, GH

Tx underlying cause
Glucose 1520 g
Glucagon w/ risk of severe

WHIPPLE TRIAD hx of
hypoglycemia, confirmed BG
of 45 or <, immediate
recovery w/ glucose admin

Serum insulin + Cpeptide

(for endogenous insulin)+
proinsulin levels in presence
of hypoglycemia
Sulfonylurea screen ()
Ketone levels low
TRI > 150
HDL < 40

Surgical resection
Diazoxide until surgery
AE = sodium retention, CHF,
hirsutism

Much higher risk of

developing DM type II,

insulin resistance similar to

DM type II

Metabolic Syndrome
(PreDiabetes/ Syndrome
X)
Type I DM

Autoimmune 90%
Little to no endogenous
insulin secretion
Plasma glucagon elevated
Pancreatic B cells fail to
respond to stimuli
destruction
Mumps, coxsackie B4 virus
infection
Toxic chemicals
Young age

3 Ps polyuria, polydipsia,
polyphagia
rapid weight loss despite
normal appetitive
blurred vision
pruritis
weakness
postural hypotension
paresthesias
vulvovaginitis
untreated can lead to DKA
(see sx above)

HTN
IFG > 100 125
Waist circumference > 40 for
M/ > 35 for W
A1c 5.76.4
random PG > 200 w/ classic
sx or FPG > 126
A1c

increased risk for elevated

plasma TRIs, lower HD,
higher BP

Type II DM

Genetic
Ethnicity: American Indians/
Alaskan Natives w/ highest
risk
Middle to older age
Overweight/ obesity

Polyuria, polydipsia
Ketonuria/ wt loss RARE
Fatigue
Pruritus
Recurrent candida vaginitis
Chronic skin infections
Blurred vision
Poor wound healing

FPG 100125
Diabetic dyslipidemia w/
high TRI, low HDL,
alterations in LDL

Diabetic Ketoacidosis

M/C W/ DM TYPE 1

Infections 3050%
Inadequate Insulin tx
2040%
MI, Ischemia, infarct (silent
in DM) 36%
CVA

3 Ps polyuria,
polydipsia, polyphagia
Wt loss
Vomiting
Abd pain (mimics
appendicitis)

pH < 7.30 to <7.00 if severe

plasma glucose > 250
serum bicarb 1018
urine ketones ++
serum ketones ++
anion gap > 10

Diet well balanced 4565% carbs, 1035%

protein, 2535% fat, chol
limited to 33 mg/day, high
fiber
Multiple dose
insulin injections or
continuous subQ
infusion
Exercise
Flu, penumococcla, Hep B
vaccine
Continuous glucose
monitoring
Low dose ASA
Diet
Exercise
Oral hypoglycemic agents
o M/C sulfonylureas
Metformin = DOC
Thiazolidinediones
Insulin
Careful foot care, meticulous
personal hygiene, promote tx
of infections
Daily ASA (81 mg)
HTN therapy for BP 130/80
HDL < 100
Annual ophthalmologic
exams, urine albumin, serum
creatinine
Flu, pneumococcal, Hep B
vaccine
Bariatric surgery for those w/
BMI > 35
5% death w/ treatment
IVF large bore catheter (1L
w/in first hour)
Insulin Bolus (will correct
high extracellular K+)

Hyperosmolar
Hyperglycemic State (HHS)
~15% mortality
M/C w/ DM type II

PE
Obstruction
RF
Burns
Prescription
Drug related

Dehydration tenting of
skin, dry mucosa, no tear
production in children
Clouded sensoria
PEpoor skin turgor,
hypotension, AMS, shock,
KUSSMAUL respirations
Stupor
Coma

elevated serum K+

Electrolyte Replacement
Na, K, Phosphate, Mg,
Bicarb (dont treat K+ w/
replacement until neutralize
insulin)

pH > 7.30
plasma glucose >
600 (8002400)
serum osmolarity > 320
serum bicarb > 15
urine ketones small
serum ketones small
anion gap > 12

fluid replacement
Insulin 0.1 unit/kg followed
by insulin infusion of 0.1
unit/kg/hr then subQ w/
levels around 250
Potassium may be indicated
Phosphate if severe
hypophosphatemia develops
during insulin therapy

DM COMPLICATIONS

DM Neuropathy

Autonomic Neuropathy

M/C form consequence of chronic hyperglycemia, affects up to 50%

Sensory deficits
o Small fibersloss of temp, pins/ needles, numb, cold, swelling, contact pain
o Large fibersloss of balance/ position sense, unable to feel feet when walking
o Motor nerve damageloss of muscle tone in hands/ feet
o Foot deformities callus, charcot joint, deformation of toes/ feet, open sores/
ulcers on feet
Motor neuropathy:leads to muscle atrophy weakness/ changes in foot shape
allows flexors to predominate
o Foot takes on a pes cavus shape w/ high arch/ prominent metatarsal head
o Toes become deformed in hammer/ claw shape irregular wt bearing/ areas of
high plantar pressure
o May lead to subtle changes in posture/ gain changes in wt bearing/ plantar
pressure
Charcot Footpartly related to autonomic neuropathy w/ vasodilation & shunting
of blood flow bone demineralization/ oosteolysis
o Acute stage= foot warm, swollen, erythematous BOUNDING PEDAL PULSES
o Pain/ tenderness may be present
o Changes occur in forefoot, midfoot, hindfoot M/C = collapse of longitudinal
arch
*** pts should check their own feet every day

Neurogenic bladderdiminished urinary frequency, incomplete emptying,

frequent UTIs, hydronephrosis, renal calculi, post void residual > 150 mL
Gastroparesisdelayed gastric emptying, early satiety/ reflux, anorexia, wt loss,
erratic blood glucose levels, hypoglycemia, dumping syndrome
DM Enteropathyfecal incontinence, diarrhea (nocturnal)
CVorthostatic hypotension, fixed HR, painless MI, sudden death, hypotension w/
exercise

CAD, PVD, CVA

Blood Pressure

Dyslipidemias

Nephropathy

Retinopathy

Other eye disorders

Skin, Teeth

Vaccination

Sudomotorareas of symmetrical anhidrosis, gustatory sweating

Pupillarydecreased/ absent response to light, decreased pupil size
Erectile Dysfxn
o Males= retrograde ejaculation, impotence
o Females= diminished vaginal lubrication, dec frequency of orgasm
CVD death rates = 1.7% higher
MI = 1.8% higher
Stroke = 1.5% higher
GOAL = 140/90 or lower
Tx w/ ACE or ARB
Lifestyle modifications
Reducing Fats
Wt loss
Exercise
Statins
Kidney disease screen for microalbuminuria at dx for type II, after 5 years of ds w/
type I serum Cr should be measured annually to measure for GFR in all adults w/
DM
TX: lifestyle, wt loss DASH diet, EToH, exercise, control HTN w/ ACE or ARB,
monitor serum K+, correct LDL, protein restriction, refer to specialist
RF= duration of DM, age, pregnancy, puberty, genetic predisposition, renal disease,
HTN, smoking, HLD, control of DM
after 20 years 90% of DM type I/ 80% of DM type II on insulin
25% of type II have it by the time they are dx
Non proliferative Mildmay be reversible, usually asymptomatic, on exam
vascular microaneurysms, dot/ flame hemorrhages, cotton wool spots, hard exudates
Non Proliferative modseverevenous caliber changes/ beading, IRMA, capillary
loss, retinal ischemia, extensive intraretinal hemorrhages/ microaneurysms
Proliferativeneovascularization
Common Senile cataractsoccur at younger age/ progress more rapidly
DM cataractsrare associated w/ osmotic abnormalities, can mature in days/
progress rapidly
Ocular Palsiesdiplopia/ strabismus from impairment of extraocular muscles due
to ischemia of CN 3,4,6
Open Angled glaucoma
Blurred Vision
Hypoglycemia visual changestemporary diplopia, flashing lights, dimming of
vision
Skin: Higher risk of infections furuncolosis/ carbuncles, candida (genitalia, upper
thighs, under breast), cellulitis w/ vascular ulcerations
Periodontal diseasechanges in gum membrane/ microflora, impaired collagen
metabolism, altered leukocyte fxn
Caries increased
Dental exam q 6 months
Altered immune fxn

Clotting Risks

IMMUNIZATIONS = EFFECT/ REDUCE HOSPITALIZATION

o Flu
o Pneumococcal
o Hep B Series
Increased production of thromboxane
ASA given to block thromboxane release in type II by acetylating platelet
cyclooxygenase