Labdxtransfinals PDF
Labdxtransfinals PDF
Labdxtransfinals PDF
UNCONJUGATED HYPERBILIRUBINEMIA
Occurs when serum B1 is >1.2 mg/dL and <20% of the
total bilirubin consists of B2
Causes:
o Hemolytic disorders
o Defective hemoglobin formation
o Impaired hepatic uptake or conjugation of
bilirubin
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L-08 LIVER FUNCTION TESTS
URINE BILIRUBIN
B1 is nonfilterable by the glomerulus, and do not NORMAL SERUM ALBUMIN:
appear in urine. o Acute viral hepatitis
B2 is water soluble, can be filtered by the glomerulus, o Drug-related hepatotoxicity
and can be detected in urine. o Obstructive jaundice
Absence of bilirubinuria in the presence of jaundice HYPOALBUMINEMIA:
implies unconjugated hyperbilirubinemia. o Ascites (dilution)
False(+) dipstick test can occur in urine: o Chronic inflammatory processes
o From women with UTI who are taking o Protein-losing enteropathies
phenazopyridine HCI or phenothiazine-containing o Nephrotic Syndrome
drugs o Malnutrition
False(-) dipstick test can occur in urine:
o In specimens left standing (delay in U/A) due to ENZYME TESTS USED TO ESTABLISH THE PRESENCE
photooxidation and hydrolysis of urinary bilirubin OF HEPATOCELLULAR DAMAGE
ASPARTATE AND ALANINE AMINOTRANSFERASE
TEST FOR HEPATIC SYNTHETIC FUNCTION Used as sensitive indicators of hepatocellular injury
PROTHROMBIN TIME NV: 5 to 40 U/L
Measures the time (seconds) required for a patient's
citrated plasma to cause the formation of fibrin clot by ASPARTATE AMINOTRANSFERASE (AST/SGOT)
converting prothrombin (synthesized in the liver) to Present in Liver, Heart, Skeletal muscle, Brain, Kidneys
thrombin, and subsequently thrombin catalyzes the Within liver:
polymerization of fibrinogen to fibrin. o 80% is found in the mitochondria
NV: 12 to 15 seconds o 20% in cytoplasm
PT is influenced by the quality and quantity of CFs (i.e., I, Alcohol is a mitochondrial toxin:
II, V, VII, X) synthesized in the liver (EXTRINSIC o Serum AST/ALT ratio (De Ritis quotient), if >2.0
PATHWAY) suggestive of Alcoholic Liver Disease
PROLONGED PT is usually caused by:
o Medications that inhibit CFs (II, VII, IX,X) ALANINE AMINOTRANSFERASE (ALT/SGPT)
o Congenital deficiency of CFs Only small amounts are found in tissues other than
o Vitamin K deficiency due to obstructive the liver
jaundice, steatorrhea, or antibiotics that alter More specific indicator of hepatocyte injury
the intestinal flora that produce Vitamin K or Almost all located within cytoplasm
inhibit the intrahepatic recycling of vitamin K If serum ALT level is high, regardless of the magnitude
o Inadequate utilization of Vitamin K due to liver of the AST/ALT ratio, acute or chronic hepatitis (viral or
dysfunction (can be differentiated from: drug-induced) or a cholestatic process is more likely.
Vit. K deficiency by parenteral
administration of Vit. K to the patient;
Correction of the PT indicates Vit. K
deficiency, while in patients with liver
disease, the PT remains prolonged)
PT test is NOT a sensitive test for liver disease (may
be normal in patients with cirrhosis)
PT is useful in the following situations:
o Follow-up of patients with acute liver injury due
to:
Acute viral hepatitis
Alcoholic steatonecrosis
Acetaminophen toxicity
o PT result >4 to 5 secs above the ULN (upper
limit of normal) that is NOT responsive to Vitamin
K therapy indicates extensive hepatic damage
and poor long-term prognosis.
o Screening test for estimating the likelihood of
intraoperative or perioperative bleeding
problems in patients undergoing surgical
procedure.
ALKALINE PHOSPHATASE (ALP)
ALBUMIN LEVEL
Present in Bone, Liver, Leukocytes, Intestine, Placenta
Main osmotic colloid of plasma, synthesized exclusively by
Principal ALP isoenzyme found in serum from healthy
the liver
persons is derived from the BONE
NV: 3.5 to 5.6 g/dL (35-45 g/L)
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L-08 LIVER FUNCTION TESTS
Increased in serum ALP concentration: GAMMA-GLUTAMYLTRANSFERASE (GGT)
o Children Increased serum concentration of GGT is NOT due to
o Puberty hepatocyte damage but secondary to increased
o Pregnant women enzyme production (like ALP)
o Liver or Bone disease o Alcohol ingestion is one of the more common
Increased serum concentration of ALP is NOT due to causes of an increased serum GGT level, also,
hepatocyte damage but results from increased synthesis drugs (phenytoin and acetaminophen)
of hepatic ALP. • Used as screening tool for identifying
Stimulus for increased ALP production: alcoholics, as well as during treatment and
o Bile duct obstruction follow-up of alcoholic patients
o Intrahepatically by infiltrative or space-
occupying lesions (i.e., metastases)
o Extrahepatically by stones, stricture, or tumor SERUM SEROLOGIC STUDIES
Serum ALP concentration- sensitive indicator of HEPATITIS B SURFACE ANTIGEN
intrahepatic or extrahepatic cholestasis: Those who clear the virus and develop immunity, HBsAg
o Markedly increased ALP levels suggest becomes undetectable and replaced by anti-HBs.
Obstruction Persistence of HBsAg in the serum for >6 months
o Modestly increased levels suggest indicates chronic carrier state, which may or may not be
Hepatocellular injury associated with active hepatitis.
Long-term carrier state for HBV is a risk factor for the
development of hepatocellular CA.
ANTIBODY TO HBe
Anti-HBe becomes detectable in serum when HBeAg has
been cleared (like anti-HBs), and generally indicates
resolution of acute infection
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L-08 LIVER FUNCTION TESTS
ANTIBODY TO HBc ANTI-SMOOTH MUSCLE ANTIBODIES
Initial Antibody produced: SMOOTH MUSCLE ANTIBODIES
o IgM anti-HBc indicates recent HBV infection; Directed against actin filaments in the cytoplasm of
o Replaced by IgG which is detectable in serum for hepatocytes
life Found commonly in the serum (60%) of patients with
Early in acute HBV infection, when HBsAg has chronic autoimmune hepatitis
disappeared but anti-HBs has not yet reached detectable Detectable levels of SMAs are found:
levels (window period), the presence of IgM anti-HBc o (<5%) in serum from healthy persons
may be the only clue to the presence of infection. o Primary biliary cirrhosis
o Acute viral hepatitis
ANTIBODY TO HEPATITIS C AND RNA DETECTION o Infectious Mononucleosis (IM)
HCV is responsible for most parenterally transmitted o chronic HCV infection
cases of non-A, non-B hepatitis
Laboratory tests for detecting HCV infection: ANTI-MITOCHONDRIAL ANTIBODIES
o 1. First-generation EIAs- screening test, Found in <1% of healthy persons, in up to 94% of primary
lacked sensitivity and specificity biliary cirrhosis, and approximately 25% of chronic active
Autoimmune chronic active hepatitis and hepatitis.
alcoholic liver disease caused False(+) Useful in evaluating patients with jaundice (serum from
results patients with jaundice due to extrahepatic biliary
o 2. Second-generation EIAs- increased obstruction will be negative for AMAs).
sensitivity and detect Ab earlier (6 weeks after
onset); low specificity SERUM PROTEIN MARKERS FOR HEPATIC DISEASE
o 3. Recombinant Immunoblot Assay (RIBA)- α-FETOPROTEIN
more sensitive and more specific Major serum protein in the fetus synthesized by fetal yolk
Detection of HCV RNA by the PCR (Polymerase Chain sac cells and embryonic hepatocytes
Reaction) is well correlated with HCV transmission. Diagnostic usefulness of AFP:
o Identification of hepatocellular CA
If anti-HCV is (–) and index of suspicion is high, then o Serum AFP levels >400 ng/mL (95%)
HCV RNA is performed because it is well correlated with Serum AFP level:
HCV transmission o Modestly increase in Yolk Sack Tumor
o Mildly increase in alcoholic liver disease,
ANTIBODY TO HEPATITIS A chronic hepatitis, and cirrhosis (100-200
Infection with HAV results in ACUTE HEPATITIS only ng/mL)
Anti-HAV is present and detectable in serum at the onset Valuable for follow-up and detection of recurrent
of infection and persists for life disease
IgM anti-HAV- persists in the serum for 3-12 months;
diagnostic marker of acute HAV infection CERULOPLASMIN
Glycoprotein synthesized in the liver, an acute-phase
reactant, a copper-containing oxidase enzyme and Cu+
donor
Prinicipal role:
o Diagnosis of WILSON’S DISEASE
(hepatolenticular degeneration)
Rare disease, characterized by:
Decreased serum ceruloplasmin
Levels
Increased urine ceruloplasmin levels
Accumulation of Cu in hepatocytes,
cornea (Kayser Fleischer rings), and
brain
Accumulation of Cu within hepatic parenchyma eventually
leads to cirrhosis.
α1-ANTITRYPSIN (AAT)
Glycoprotein synthesized in the liver, an acute-phase
reactant, and inhibitor of proteolysis by serine
proteases (chymotrypsin, elastase)
AAT deficiency is associated with lung and liver disease:
o Pulmonary emphysema
o Cholestatic liver disease or cirrhosis
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L-08 LIVER FUNCTION TESTS
ACUTE-PHASE REACTANTS
Refers to proteins that increases during episodes of
acute inflammation (eg, infection, surgery, myocardial
infarction)
o AAT
o Ceruloplasmin
o CRP (C-Reactive Protein)
KEY POINTS
1. If the possibilities of hemolysis and defective
Hemoglobin formation have been excluded, an
increased serum bilirubin level is typically an
indication of hepatobiliary dysfunction.
Source:
Dr. Mila Amor Reyes, ppt lecture presentation
5 CASTILLO, J.LP.
LABORATORY DIAGNOSIS
2A RENAL FUNCTION TESTS
L-09 Dr. Mila Am or Reyes | A.Y. 2018 -2019
Using the mass balance principle, if substance X is
Topic Outline neither absorbed, metabolized, nor secreted along journey
from Bowman's space to the urinary bladder, then the
I. Renal Physiology amount of substance X entering Bowman's space, is equal
II. Glomerular Filtration Rate to that eliminated in the urine.
Inulin GFR= CuVu/Ca Vcl= GFR
III. Creatinine GFR is age dependent:
IV. BUN o Maximum is achieved during the 3rd decade of
V. Renal Concentrating Capacity life and decreases at the rate of 1 mL/min/year
VI. Osmolality from the 5th decade onward
VII. Specific Gravity For substances that are secreted by renal tubular
VIII. Water Deprivation Test epithelial cells into the tubular lumen, their urinary
IX. Diabetes Insipidus concentration will be elevated, and the calculated
X. Renal Diluting Capacity clearance of these substances will overestimate the true
GFR.
RENAL PHYSIOLOGY For substances that are reabsorbed along the nephron,
their urinary concentration will be decreased, and the
Normal kidney function depends on: calculated clearance will underestimate the true GFR.
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L-09 RENAL FUNCTION TESTS
METHODS OF CREATININE DETERMINATION BLOOD UREA NITROGEN (BUN)
End product of protein catabolism
1. JAFFE REACTION- alkaline picrate chromogenic assay Produced in the liver via the urea cycle, which converts
Colorimetric determination of creatinine-picric acid ammonia, derived from the breakdown of proteins, to
complex urea.
Interfering chromogens: results in falsely high Affected by:
values o Excessive protein catabolism (e.g., febrile
o Protein illness)
o Urea o Inhibition of anabolism (e.g., treatment with
o Glucose corticosteroids)
o Ascorbic Acid (Vitamin C) Synthesis is also dependent on intact liver function
o Guanidine NV:
o Acetone o 10 to 15 mg/dL (3.6-5.4 mmol/L)
o Cephalosporins
o a-ketoacids o Low values: (<10 mg/dL or 3.6 mmol/L) are
(PU GAGA CA ) associated with overhydration
o High values: (50-150 mg/dL or 17.9-53.6
2. ENZYMATIC METHOD- enzymatic degradation of mmol/L) signify impaired renal function
creatinine with creatinase o Markedly elevated BUN concentration: (150-
250 mg/dL or 53.6- 89.3 mmol/L) is virtually
Measuring Creatinine Clearance (ClCr) is time- conclusive evidence of severe renal
consuming and labor-intensive. dysfunction
Serum Creatinine (SCr) concentration is often Urea is filtered by the glomeruli but is also significantly
used to estimate renal function and GFR. reabsorbed by the renal tubular epithelium; amount
Inverse relationship between GFR and Serum Creatinine reabsorbed is inversely proportional to the urinary
(Scr): flow rate.
o e.g., in a patient with an initial serum creatinine Amount reabsorbed is inversely proportional to the urinary
concentration of 0.6 mg/dL (53 µmol/L) and an flow rate.
initial GFR of 100 mL/min, a decrease in GFR to BUN is NOT as useful a measure of renal function as is
25 mL/min would raise the SCr to 2.4 mg/dL Serum Creatinine (SCr) but may correlate better with
(212 µmol/L) uremic symptoms than SCr concentration.
Two (2) instances in which serum creatinine concentration In patients with very low GFRs consistent with severe
may be FALSELY ELEVATED without indicating a renal disease:
significant decrease in GFR: o Creatinine clearance (ClCr) significantly
o MASSIVE RHABDOMYOLYSIS- associated with overestimates the true GFR
rapid release of large quantities of skeletal o BUN clearance (ClBUN) consistently
muscle-derived creatinine into the blood. underestimates GFR
o Drugs (e.g., cimetidine)- interfere with o Note: If the clearances are averaged, a relatively
tubular secretion of creatinine accurate estimate of the true GFR can be
Measurement of Creatinine Clearance (ClCr) as an obtained.
estimate of GFR requires measurement of:
o Serum creatinine (SCr) concentration METHODS OF BLOOD UREA NITROGEN DETERMINATION
o Urine creatinine (UCr) concentration 1. INDIRECT METHOD- which generates NH4+ from urea
o 24-hour urine volume through the use of bacterial enzyme urease.
NH4+ is detected in a coupled reaction in which
Sample Calculation: glutamate dehydrogenase converts α-ketoglutarate to
A 70-kg man collects 1.7L of urine over 24 hours. SCr is glutamate with simultaneous oxidation of NADH to NAD
1.1 mg/dL ((97 µmol/L) and UCr is 82 mg/dL (7248 o Falsely low result: Citrate or Fluoride can inhibit
µmol/L) urease
o Falsely high result: Endogenous NH3
2. COLORIMETRIC METHOD- condensation of urea with
diacetyl group to form a chromogen, whose concentration is
measured spectrophotometrically.
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L-09 RENAL FUNCTION TESTS
o Obstruction of the urinary tract DIABETES INSIPIDUS
o Excess urea production from GIT bleeding, In NEUROGENIC DI- ADH deficiency; patients will
fever, or catabolic drugs respond to the exogenously administered ADH with
Decreased BUN: SCr – seen in: concentrated urine and return of the elevated serum
o Low-protein diets osmolality to normal.
o Chronic hemodialysis (because urea is more In NEPHROGENIC DI — collecting duct epithelium
efficiently dialyzed than creatinine) unresponsive to ADH with normal ADH level; patients will
o Pregnancy (due to increased GFR, which has a continue to produce large quantities of dilute urine with
greater effect on urea excretion relative to rising serum osmolality.
creatinine excretion) Defective renal tonicity may cause an abnormal
deprivation test:
RENAL CONCENTRATING CAPACITY o Can be cause by drugs (e.g., furosemide),
The ability of the kidney to concentrate or dilute the ischemia, sickle cell disease, or compulsive
urine is important and complements the thirst water drinking
mechanism in maintaining the appropriate osmolality of
the plasma and extracellular fluid. RENAL DILUTING CAPACITY
NV: 280-290 mOsm/kg water Tests of renal dilution, or the ability to excrete free water
NOT commonly performed because of the potentially
OSMOLALITY serious adverse sequelae associated with water
Measure of the number of solute molecules in solution, intoxication.
independent of the size of the individual molecules.
Measured by comparing the freezing point of a solution KEY POINTS
with that of distilled water. 1. Creatinine clearance measurements are useful in
The more concentrated a solution is, the higher its estimating GFR and in assessing renal function.
osmolality, and the lower its freezing point.
2. Both colorimetric and enzymatic methods are available
SPECIFIC GRAVITY for quantifying urine and serum creatinine concentrations used
Ratio of the mass per unit volume of a solution, to the in the calculation of creatinine clearance.
mass per unit volume of distilled water (SG= 1.000)
Affected by the size and number of particles in solution, 3. Urine creatinine measurements are useful in assessing
measured by a hydrometer or a REFRACTOMETER. the adequacy of 24-hour urine collections. A healthy 70-kg
Plasma and urine with an osmolality of 300 mOsm/kg man normally excretes approximately 20 mg per kg day in the
water has a SG of 1.010. urine.
Very dilute urine has a SG of 1.000 to 1.001.
Moderately concentrated urine has a SG of 1.020. 4. Measurement of both creatinine and BUN clearances are
Urine with SG >1.022, in the absence of glucose, protein, useful in obtaining an estimate of GFR in patients with severe
or radiocontrast material, suggests intact renal renal disease.
concentrating capacity.
5. Urine SG measurements are used to estimate urine
Healthy kidneys can vary the osmolality (or tonicity) of
osmolality;
the urine from 50 mOsm/kg water (i.e., dilute or
hypotonic with respect to plasma) to 1200 mOsm/kg
6. Urine SG values greater than 1.022 suggest intact renal
water (concentrated or hypertonic) depending on the
concentrating ability in the absence of interfering substances
solute load and free water balance.
such as glucose, protein, or radiocontrast material.
WATER DEPRIVATION TEST
7. The water deprivation test, supplemented by
Water deprivation results in:
administration of ADH, is useful in discriminating between
o Concentrated urine (elevation of serum
neurogenic DI and nephrogenic DI.
osmolality), with release of ADH or vasopressin
which acts on the renal collecting ducts to
8. Tests of renal diluting capacity are NOT commonly
facilitate reabsorption of free water, and
performed because of potential adverse sequelae associated
o Stimulation of the thirst response
with water intoxication.
Test of renal concentrating ability.
Performed on patients who produce persistently dilute
urine.
o Measurement of body weight, serum and urine
osmolality, and serum ADH concentration at the
beginning and at the end of the test
o Careful monitoring of the patient to avoid marked Source:
dehydration Dr. Mila Amor Reyes, ppt lecture presentation
o If the polyuric patient shows minimal evidence of
concentrating ability, a small dose of ADH is
administered, and serum and urine osmolalities
are measured
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LABORATORY DIAGNOSIS
2A ENDOCRINE FUNCTION TESTS
L-07 Dr. Mila Am or Reyes | A.Y. 2018 -2019
PITUITARY FUNCTION ADRENOCORTICOTROPIC HORMONE (ACTH)
Synthesis and secretion by the anterior pituitary is Mainly stimulates the synthesis and secretion of
controlled by the hypothalamus via hypophysiotropic glucocorticoids, with minor effect on mineralocorticoids
homones, and by the hormones of target glands and adrenal androgens.
"negative feedback“ Secretion is stimulated by:
Hormones secreted by the anterior pituitary: o Many types of stress
o Growth Hormone o Hypoglycemia
o Luteinizing Hormone Inhibited by cortisol
o Follicle-stimulating Hormone Secreted in a pulsatile manner with diurnal rhythm
o Thyroid-stimulating Hormone (highest in early morning hours)
o Adrenocorticotropic Hormone
o Prolactin THYROID-STIMULATING HORMONE (TSH)
Immunocytochemical and electron microscopic techniques Stimulates the growth and function of the thyroid
allow the cells of the anterior pituitary to be classified gland (to produce T3 and T4).
according to their secretory products: Secretion is regulated by the:
o ACIDOPHILS: o Levels of thyroid hormones
Somatotropes secrete Growth o Thyrotropin-releasing hormone (TRH)
Hormone
Lactotropes secrete Prolactin PROLACTIN
o BASOPHILS: Primary effect is the initiation and maintenance of lactation
Thyrotropes secrete TSH in the postpartum period.
Corticotropes secrete ACTH Secretion is increased by stress, under tonic inhibition by
Gonadotropes secrete gonadotropins dopamine.
Secreted in an episodic and pulsatile manner
LH & FSH
Gonadotropins β-sub-unit confers the biologic specificity
of the hormone.
In men:
o LH acts on Leydig cells to increase the
synthesis and secretion of testosterone;
o FSH acts on Sertoli cells and stimulates
spermatogenesis
o Sertoli cells produce inhibin, which inhibits FSH
secretion
In women:
o LH stimulates estradiol and progesterone
production by the ovary;
o FSH is responsible for the development of the
ovarian follicle
GROWTH HORMONE (GH)
o LH surge in the mid-menstrual cycle is
Stimulates linear growth mediated by somatomedins
responsible for ovulation, and maintains the
or IGFs, which stimulate protein synthesis.
corpus luteum and progesterone production.
Stimulates lipolysis with antagonistic effect on insulin
FSH and LH are under dual control of the
action.
hypothalamus and gonads;
Secretion is stimulated by:
Secreted in an episodic manner
o Exercise
Gonadotropin-releasing hormone (GnRH):
o β-blockers
o Maintains basal gonadotropin secretion
o Amino acids
o Generates the phasic release of gonadotropins
o Dopamine
for ovulation
o Glucagon
o GHRH o Determines the onset of puberty
o Sleep
HYPOPITUITARISM
o Stress (hypoglycemia)
(E BAD GG SS ) Deficiency of one or more pituitary hormones
(panhypopituitarism)
o Clinical manifestations are not evident until at
Secreted in an episodic and pulsatile manner
least 75% of the gland is destroyed
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L-07 ENDOCRINE FUNCTION TESTS
Causes of Hypopituitarism: Cortisol and GH reserve- assessed by insulin-induced
o Tumors hypoglycemia
o Trauma Vascular disease (Sheehan's syndrome) o Following the inducement of adequate
o Irradiation hypoglycemia (40 mg/dL), cortisol levels should
o Granulomas be >20 ug/dL and GH levels should be 10 ng/mL
(TT IG ) o In children with suspected GH deficiency:
Screening test with either L-dopa,
GH DEFICIENCY- no obvious clinical manifestations glucagon, or exercise
but may contribute to: must be undertaken initially;
o tendency to fasting hypoglycemia in adults; If GH response is inadequate (<5
o longitudinal growth is severely retarded in ng/mL)—proceed to insulin-induced
children hypoglycemia test
TSH DEFICIENCY- “secondary hypothyroidism”
producing clinical picture similar to primary hypothyroidism PITUITARY TUMORS
with weakness, bradycardia, and delayed reflexes. Most common cause of hypopituitarism, constitute 10%
of all intracranial tumors, classified into:
ACTH DEFICIENCY- major clinical feature is tendency to o Secretory
spontaneous hypoglycemia without hyperpigmentation o Non-secretory
present with primary hypoadrenalism. Craniopharyngioma- Most common pituitary tumor in
children
PROLACTIN DEFICIENCY- major consequence is failure Pituitary adenoma- Most common pituitary tumor in
of lactation, usually seen in Sheehan's syndrome. adults (<10mm diameter—microadenoma)
Manifestations:
GONADOTROPIN DEFICIENCY (LH & FSH): o Space-occupying lesions
o Results in delayed or partial puberty in children o Hypopituitarism
o More common in males o Hypersecretion of hormones
o KALLMANN'S SYNDROME- associated with
midline defects, nerve deafness, color-blindness,
and anosmia. CRANIOPHARYNGIOMA
o After puberty, clinical features in males include: Develop from Rathke’s pouch
Impotence Suprasellar, non-secretory, and most are cystic
Loss of libido Most common pituitary tumors in children and young
Loss of secondary sex adults
characteristics (facial, pubic, and Clinical Presentation/s:
axillary o Raised ICP
hair loss) o Visual field defects
Infertility (oligo- or azospermia) o Hypopituitarism
o Women may present with: “Suprasellar calcification” (>70%) — hallmark of this
Dyspareunia tumor
Loss of libido
Loss of secondary sex ACROMEGALY
characteristics Increased secretion of GH before epiphyseal closure
Oligomenorrhea results in gigantism, while in adults it results in
Infertility acromegaly
o Both are usually due to a GH-producing
LABORATORY INVESTIGATION OF pituitary adenoma
HYPOPITUITARISM Other causes:
Routine investigation of patients suspected of having a o Ectopic GH or GHRH secretion in patients with
tumor- assessment of visual fields and imaging studies of carcinoids
the pituitary fossa (CT scan and MRI). o Lung Cancer
Initial screening to assess pituitary function- measurement o Islet cell tumors
of TSH, free T4, LH, FSH, Prl, testosterone, and o Eutopic GHRH secretion from a hypothalamic
cortisol. hamartoma
o Pooled sample (3 samples, 20 mins. apart) Acral enlargement (skin, subcutaneous tissue, and
should be obtained for LH, FSH, Prl, and skeletal overgrowth)
testosterone. o Increasing ring, gloves, or shoe size;
Best assessment for gonadotropin deficiency in o Hyperhidrosis
premenopausal women- menstrual history. o Hypertension
Measurement of IGF-1—GH deficiency (provided the o Diabetes
patient is not malnourished, chronically ill, or elderly, since o Cardiomyopathy (CMP)
these decreases IGF-1) o Osteoarthritis
Useful index of ovulation is measurement of serum Diagnosis is usually clinically obvious and can be
progesterone (> 5 ng/mL) confirmed by assessment of GH secretion
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L-07 ENDOCRINE FUNCTION TESTS
o Fasting plasma GH levels: >5 ng/Ml DIABETES INSIPIDUS
o Single measurements are NOT reliable- pulsatile Can result from:
nature and effect of stress on GH levels o Failure of ADH secretion (neurogenic, cranial or
o Simplest and most specific test: GH response to central)
the administration of 100g oral glucose o Failure of the kidneys to respond to ADH
Normal Value- GH levels are (nephrogenic)
suppressed to <2 ng/mL at 60 mins. Neurogenic, cranial or central DI- will develop if 80% of
Acromegaly- do not suppressed the pathways are destroyed; rare disorder
adequately o Causes: trauma, idiopathic, tumors, infections,
Measurement of IGF-1 level (somatomedin C) — vascular lesions, and granulomas
elevated in Most common form of DI- idiopathic type (30%)
virtually all patients o Essential feature is “polyuria” (3-15 L) with dilute
Criteria that constitute an adequate response to therapy: urine
o 1. basal GH level <5 ng/Ml o Can lead to hypertonic dehydration, which in
o 2. adequate suppression following intake of turn stimulates the thirst mechanism, resulting in
oral glucose polydipsia
o 3. normal level of IGF-1 WATER DEPRIVATION TEST- most common provocative
test
PROLACTINOMAS o Patients are dehydrated until hourly urine
Most common secretory tumors of the pituitary osmolalities are constant (<30 mOsm/kg
gland: difference between consecutive samples);
o 8x more common in women plasma osmolality is obtained and ADH
Women can present with: administered
o Galactorrhea
o Amenorrhea o Normal persons and in psychogenic
o Loss of libido polydipsia- urine osmolality > plasma osmolality
o Anovulation (300 mOsm/kg) at the end of dehydration and
o Infertility does NOT increase by >5% following ADH
o Effects of tumor expansion
Men may present with: o In partial DI- urine osmolality > plasma
o Galactorrhea osmolality at the end of dehydration and
o Impotence increases by at least 9% following ADH
o Loss of libido
o Gynecosmastia o In severe DI- urine osmolality < plasma
o Infertility osmolality at the end of dehydration and
o Effects of tumor expansion increases by >50% following ADH
In microadenomas- rest of pituitary function is
normal, basal testing of pituitary hormones o Should be terminated if body weight falls by >3%
o In macroadenomas- assess for hypopituitarism
Several random measurements of Prolactin level with Another useful test — ADH response to a hypertonic
pooled samples- most reliable test saline infusion or maximum dehydration, if ADH assays
are available.
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L-07 ENDOCRINE FUNCTION TESTS
THYROID FUNCTION
Because thyroid dysfunction is common, clinical
assessment is frequently undertaken
It is essential to the integrity of the organism to closely
regulate thyroid metabolism
o Remarkably narrow “setpoint” for fT4 and fT3
(metabolically active form)
Because >99% of T 4 and T3 is protein bound
(essentially inert), measurement of total levels is
misleading because it primarily reflects levels of binding
proteins, not thyroid function
o Bound hormones are reservoir for future release
to the tissues
TSH assay alone is superior as a clinical test for subtle
thyroid abnormalities — will result in a sensitive and rapid
inverse change in the TSH level.
TESTING STRATEGIES:
For symptomatic patients — TSH-based testing is
effective for both hypothyroidism and hyperthyroidism
If either is clinically suspected — measurement of both
TSH and fT4 indicated
For screening asymptomatic patients — only TSH is
needed; fT4 is indicated only if TSH is abnormal
Other Secretory Tumors:
Undetectable TSH level, with or without fT4 elevation:
o CUSHING’S DISEASE- 3rd most common
o Autoimmune hyperthyroidism
secretory disorder of the pituitary gland due to
o Toxic nodular goiter
excess ACTH secretion
o Exogenous thyroxine overdose (most common)
o Pituitary tumors secreting glycoprotein hormones
(TSH, LH, & FSH)—uncommon
KEY POINTS
1. Disorders of the pituitary gland include syndromes of
excess and syndromes of deficiency.
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L-07 ENDOCRINE FUNCTION TESTS
KEY POINTS
1. Free thyroid hormone levels are maintained within a
narrow range.
Clinical features:
o Weight loss
o Skin pigmentation
o Hypotension
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Biochemical features: Useful CONFIRMATORY TESTS:
o Hypoglycemia o Examination of the diurnal variation of
o HypoNa+ cortisol levels
o HyperK+ o Urinary free cortisol test
o Metabolic acidosis o Overnight dexamethasone and low-dose
o Azotemia dexamethasone suppression test
RAPID ACTH STIMULATION TEST- most useful In Cushing’s syndrome- diurnal variation is absent and
confirmatory test plasma cortisol levels in the later part of the afternoon and
o 250 µg cosyntropin is injected IM or IV, and at night >10 µg/dL
cortisol levels are obtained at baseline, and 30 to
60 mins following injection URINARY FREE CORTISOL- very sensitive test,
o NV: basal cortisol > 6 µg/dL, the increment over increased in 95%
basal > 7 µg/dL, and peak value > 20 µg/dL
o Subnormal response- consistent with OVERNIGHT DEXAMETHASONE SUPPRESSION
adrenocortical insufficiency TEST- 1mg dexamethasone is given at 11:00 PM and
o Normal response- does not rule out an impaired cortisol level is obtained at 8:00 AM the next morning
ACTH reserve (partial adrenal insufficiency) due NV: <5 µg/dL
to hypothalamopituitary disease Cushing’s syndrome: >10 µg/dL
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Other causes of hypertension with hypokalemic
o In primary adrenal tumors- ACTH levels are alkalosis:
decreased, <10 pg/mL o Cushing’s syndrome
o Adrenogenital syndrome
o Ectopic ACTH syndrome — ACTH levels are o Renin-secreting tumor
elevated, >200pg/mL o Renal vascular hypertension
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KEY POINTS
1. Disorders of the adrenal gland include syndromes of
deficiency and syndromes of excess, both of which are
uncommon but potentially treatable.
Source:
Dr. Mila Amor Reyes, ppt lecture presentation
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