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16 Endocrine Testings: Suppression and Stimulation Tests
9.16 Endocrine Testings: Suppression and Stimulation Tests
Table 9.6 Common Endocrine Tests
Glucose tolerance test (GTT); for
Basal levels of FSH, LH, TSH, ACTH,
cortisol, GH, and then reanalysis of
these analytes after administration of
Basal levels of FSH, LH, TSH,
prolactin, cortisol, GH, and reanalysis
of these analytes after administration
of insulin, GnRH, and TRH.
Basal cortisol at 8À9 AM and then
the next morning after receiving
With true hyperpituitarism basal levels
will be high and will not reduce.
Triple bolus (insulin, GnRH, TRH).
suppression test (1 mg of
dexamethasone at bedtime); for
Low-dose dexamethasone test
(0.5 mg, q6h for 2 days); for
suppression test (2 mg q6h for
2 days). Done after positive low
dose dexamethasone suppression
test to differentiate Cushing’s
disease from other causes.
Short ACTH (250 μg) stimulation
test for hypoadrenalism.
Long ACTH (1 mg) stimulation test
to differentiate primary from
Basal cortisol level and reanalysis of
cortisol level after 48 hours.
With true hypopituitarism basal levels
will be low and will not rise.
Normal patients should have cortisol
below 5 μg/dL, but patients with
Cushing’s should not show any
suppression of morning cortisol level.
True Cushing’s syndrome patient will
have high levels and will not reduce.
Basal cortisol level and after
Cushing’s disease patient will show
50% or more reduction of cortisol
level; other causes of Cushing’s
syndrome will not.
Cortisol level before and after.
True hypoadrenalism patients will
have low basal levels and will not rise.
Patients with primary hypoadrenalism
will show no rise at all here as
patients with secondary
hypoadrenalism will show gradual
increase with time.
Cortisol level before and after (up to
pituitarism by measuring base levels of any of a combination of hormones,
including LH, FSH, ACTH, cortisol, and GH. Following oral administration of
glucose, values of these hormones should be suppressed, but with true hyperpituitarism, basal levels will be high and will not be suppressed following administration of oral glucose.
For diagnosis of hypopituitarism, especially dysfunction of the anterior pituitary, the bolus test (also known as the dynamic pituitary function test) is
used. In this test, three hormones, including insulin, gonadotropin-releasing
hormone (GnRH), and thyrotropin-releasing hormone (TRH), are injected in
a bolus into a patient’s vein to stimulate the anterior pituitary gland. Before
the bolus injection, baseline levels of cortisol, GH, prolactin, TSH, LH, and
FSH are measured. After bolus administration, insulin-induced hypoglycemia
should increase levels of cortisol and GH, while TRH should increase levels
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of TSH and prolactin, and levels of LH and FSH should increase due to
administration of GnRH. The serum glucose value is also measured to ensure
hypoglycemia induced by insulin. However, in a patient with hypopituitarism, levels of these hormones should stay low at baseline values despite
administration of these hormones by bolus injection.
Various dexamethasone suppression tests are useful in the diagnosis of
Cushing’s syndrome. Dexamethasone is a potent glucocorticoid that suppresses the nocturnal rise in ACTH levels and thus suppresses 8 AM cortisol
levels in a normal individual. In an overnight dexamethasone suppression
test, 1 mg of dexamethasone is given at bedtime and the serum cortisol level
at 8À9 AM is measured. In a normal individual the serum cortisol level
should be , 5 μg/dL following administration of dexamethasone; a value
over 5 μg/dL indicates Cushing’s syndrome. In a low-dose dexamethasone
suppression test, 0.5 mg of dexamethasone is administered every 6 h for two
days. The cortisol level is measured in the morning before and after administration of dexamethasone. In patients with Cushing’s syndrome, no suppression of the cortisol level is observed following administration of
dexamethasone. However, due to simplicity, a 1- mg dexamethasone suppression test is used more frequently. A high-dose dexamethasone suppression
test is useful to differentiate Cushing’s syndrome caused by adrenal tumors
and non-endocrine ACTH-secreting tumors from Cushing’s disease. This test
is usually performed after a low-dose dexamethasone suppression test or a
1-mg dexamethasone suppression test. In this test, 2 mg of dexamethasone
are administered every six hours for two days (an 8-mg total dosage), and
serum cortisol is measured in the morning before and after administration of
dexamethasone. In patients with Cushing’s syndrome, no suppression of the
morning cortisol level should be observed, but in patients with Cushing’s
disease, a 50% or more reduction of serum cortisol should be observed.
Although the glucose tolerance test is sometimes considered a gold standard
for evaluating hypothalamusÀpituitaryÀadrenal function in adrenal insufficiency, the ACTH stimulation test (also known as the cosyntropin test) is
also used to determine functional capacity of adrenal glands in evaluating
patients with suspected adrenal insufficiency. A normal individual should
show two- to three-fold increases in serum cortisol (a gradual increase with
time) within 1 h after administration of exogenous ACTH. In this test, after
administration of synthetic ACTH (tetracosactrin: 1À24 amino acid sequence
of human ACTH), if the serum cortisol level is not increased, it is indicative
of adrenal insufficiency. In the standard ACTH stimulation test (also known
as the short ACTH stimulation test), 250 μg of synthetic ACTH is administered intramuscularly or intravenously and a subnormal cortisol response
(,18 μg/dL; , 500 nmol/L) 30 to 60 min after the stimulation test is considered a positive test and indicates an increased possibility of primary or
secondary adrenal insufficiency. A value over 20 μg/dL is considered a normal response. Sometimes a long-acting ACTH stimulation test using 1 mg of
synthetic ACTH is used for differentiation between primary and secondary
hypoadrenalism. More recently, a low-dose ACTH stimulation test using only
1 μg of synthetic ACTH has been introduced. This test is useful for the diagnosis of adrenal insufficiency; however, older males may have a more
decreased responsiveness to this test than older females . Another alternative to test the function of the hypothalamusÀpituitaryÀadrenal axis is
administration of metyrapone, an inhibitor of 11 β-hydroxylase enzyme that
converts 11-deoxycortisol to cortisol. Under normal conditions, a reduced
cortisol level in plasma stimulates ACTH release and the concentration of
11-deoxycortisol in serum increases significantly; a lack of response suggests
primary adrenal failure.
Endocrine activity can be classified as autocrine, paracrine, or classical endocrine
activity. In autocrine activity, chemicals produced by a cell act on the cell itself. In
paracrine activity chemicals produced by a cell act locally. However, in classical
endocrine activity, chemicals produced by an endocrine gland act at a distant site
after their release in the circulation; these chemicals are called hormones. Most
classical hormones are secreted into the systemic circulation. However,
hypothalamic hormones are secreted into the pituitary portal system.
Receptors for hormones may be cell surface, membrane, or nuclear receptors.
Hormone secretion may be continuous or intermittent. Thyroid hormone secretion
is continuous. Thus, levels may be measured at any time to assess hormonal
status. Secretion of follicle-stimulating hormone (FSH), luteinizing hormone (LH),
and growth hormone (GH) are pulsatile. Thus, a single measurement may not
reflect hormonal status. Some hormones exhibit biological rhythms. Cortisol
exhibits a circadian rhythm where levels are highest in the morning and lowest
during late night. The menstrual cycle is an example of a longer biological rhythm
where different levels of a hormone are observed during a specific part of the
Certain hormone levels are elevated during stress. These include
adrenocorticotropic hormone (ACTH), as well as cortisol, GH, prolactin, adrenaline,
Certain hormone levels are increased during sleep, such as GH and prolactin.
The hypothalamus produces thyrotropin-releasing hormone (TRH), corticotropin
hormone (CRH), gonadotropin-releasing hormone (GnRH), growth hormone-releasing
hormone (GHRH), and somatostatin (growth hormone inhibitory hormone). These
hormones act on the anterior pituitary and result in the release of various other
hormones, including thyroid-stimulating hormone (TSH), ACTH, FSH, LH, and GH.
Somatostatin inhibits the release of GH. Dopamine (also known as prolactin inhibitory
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hormone) is also a neurotransmitter produced by the hypothalamus. Dopamine can
inhibit GH secretion.
The supraoptic and paraventricular nuclei of the hypothalamus produce
antidiuretic hormone (ADH, i.e. vasopressin) and oxytocin. These hormones are
stored in the posterior pituitary and act on certain body parts rather than on the
pituitary like other tropic hormones do. ADH acts on the collecting ducts of the
renal tubules and causes absorption of water.
Growth hormone (GH, also known as somatotropin) is the most abundant hormone
produced by the anterior pituitary, and it stimulates growth of cartilage, bone, and
many soft tissues. GH stimulates release of insulin-like growth factor-1 (IGF-1,
somatomedin C), mostly from the liver.
Hyperpituitarism is most often due to pituitary tumors affecting GH-secreting
cells, prolactin-secreting cells, and ACTH-secreting cells. GH-secreting tumors
that affect individuals before closure of the epiphyses result in gigantism, and
after closure they result in acromegaly. Prolactin-secreting tumors cause
hyperprolactinemia. A high level of prolactin (prolactinemia) inhibits action of FSH
and LH, which results in hypogonadism and infertility. ACTH-secreting tumors
cause Cushing’s syndrome.
For diagnosis of hypopituitarism, stimulation tests with GnRH, TRH, and insulininduced hypoglycemia (a triple stimulation test) is useful. Following stimulation,
serum or plasma levels of FSH, LH, TSH, PRL, GH, and cortisol are measured.
Endocrine tests for hyperpituitarism include measurement of hormone levels and a
suppression test using glucose (oral glucose tolerance). Administration of glucose
with a rise in blood glucose should suppress anterior pituitary hormones in normal
Four steps are involved in the synthesis of thyroid hormones: (1) inorganic iodide
from the circulating blood is trapped (iodide trapping), (2) iodide is oxidized to
iodine, (3) iodine is added to tyrosine to produce monoiodotyrosine and
diiodotyrosine (referred to as organification), and (4) one monoiodotyrosine is
coupled with one diiodotyrosine to yield T3 and two diiodotyrosines are coupled
to yield T4 (coupling).
Free (unbound) T4 is the primary secretory hormone from the thyroid gland. T4
is converted in peripheral tissue (liver, kidney, and muscle) to T3 by
5’-monodeiodination. T3 is the physiologically active hormone. T4 can also be
converted to reverse T3 by 3’-monodeiodination. This form of T3 is inactive. The
majority (99%) of the T3 and T4 in circulation is found to be thyroxine-binding
globulin (TBG), albumin, and thyroxine-binding prealbumin.
Dyshormonogenetic goiter may be associated with nerve deafness, referred to as
There are situations where thyroid hormone-binding proteins may be low or high,
causing alteration of total T3 and T4 levels. However, free T3, T4, and TSH levels
should be normal. Pregnancy and oral contraceptive pills raise concentrations of
thyroid-binding proteins. Hypoproteinemic states such as cirrhosis of the liver,
nephrotic syndrome, etc., may cause lower concentrations of thyroid-binding
Amiodarone can reduce peripheral conversion of T4 to T3. Free T4 levels may be
high, but TSH levels could be normal. Because it contains an iodine molecule,
amiodarone can also cause both hypothyroidism and hyperthyroidism.
Seriously ill patients may have reduced production of TSH with low T4 and
reduced conversion of T4 to T3 with increased conversion of T4 to reverse T3.
Patients are, however, euthyroid. This is referred to as sick euthyroid syndrome.
Measurement of TSH can suffer interference from heterophilic antibody and
rheumatoid antibody, causing falsely elevated results. Rarely, autoantibodies to
TSH develop clinically, but such autoantibodies can also falsely increase TSH
results. A rare interference in the TSH assay is due to macro-TSH, an autoimmune
complex between anti-TSH IgG antibody and TSH.
Primary hypothyroidism (primary disease of thyroid gland): Causes include
autoimmune thyroiditis, Hashimoto’s thyroiditis, surgery/radiation,
dyshormonogenesis, antithyroid drugs, drug therapy with amiodarone, and
Secondary hypothyroidism can be due to lack of TSH from pituitary or peripheral
resistance to thyroid hormones.
Causes of hyperthyroidism include Graves’ disease, toxic nodular (single or
multiple) goiter, thyroiditis (e.g. due to viral infection), drugs, and excess TSH (e.g.
due to pituitary tumor).
Parathyroid hormone (PTH) is an 84-amino acid hormone secreted by the chief
cells of the parathyroid, and it increases calcium levels in blood by increasing
osteoclastic activity in bone, increasing synthesis of 1,25-dihydroxycholecalciferol
(vitamin D3), increasing renal reabsorption of calcium, as well as by increasing
intestinal absorption of calcium.
Calcitonin, which is secreted by the parafollicular C cells of the thyroid, essentially
has the opposite action to that of PTH.
Hyperparathyroidism is a common cause of hypercalcemia and can be primary
(due to adenomas or hyperplasia of parathyroid glands), secondary (due to
compensatory hypertrophy of parathyroid glands due to hypocalcemia, as seen in
chronic kidney disease), or tertiary (where after a long period of secondary
hyperparathyroidism the parathyroid glands develop autonomous hyperplasia and
hyperparathyroidism persists even when hypocalcemia is corrected).
Hypoparathyroidism refers to low levels of PTH being secreted from the
parathyroid glands, whereas pseudohypoparathyroidism refers to the inability of
PTH to exert its function due to a receptor defect. Pseudohypoparathyroidism
is a hereditary disorder, and patients, in addition to hypocalcemia, also have
short stature, short metacarpals, and intellectual impairment. Pseudopseudohypoparathyroidism patients actually have no abnormality of PTH or
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parathyroid. Only the somatic features seen in pseudohypoparathyroidism are
present, but these patients do not have cognitive impairment as seen in patients
The adrenal glands consist of a cortex and a medulla. The cortex has three zones:
zona glomerulosa, zona fasciculata, and zona reticularis. The zona glomerulosa is
responsible for secreting mineralocorticoids (aldosterone), while the zona
fasciculata is responsible for secreting glucocorticoids. Finally, the zona reticularis
is responsible for producing sex steroids. The adrenal medulla produces
Congenital adrenal hyperplasia is most often due to lack of 21-hydroxylase
enzyme causing decreased production of deoxycorticosterone and aldosterone,
as well as reduced levels of deoxycortisol and cortisol. ACTH level is also high,
and as a result, 17-hydroxypregnenolone and 17-hydroxyprogesterone are
produced in higher concentrations, which leads to increased production of
dehydroepiandrosterone, androstenedione, and testosterone. Female children
suffer a virilizing effect and may also have ambiguous genitalia. Male children
have features of precocious puberty.
Major causes of Cushing’s syndrome can be sub-classified under two broad
categories: (1) ACTH-dependent disorders, which include Cushing’s disease
(ACTH-secreting pituitary tumor), ectopic ACTH-producing tumor (such as lung
cancer), and secondary due to ACTH administration; and (2) non-ACTHdependent disorders (adrenal tumor or secondary due to glucocorticoid
administration). ACTH-dependent Cushing’s syndrome is more common (70À80%
of all cases) compared to non-ACTH-dependent disorders. Among ACTHdependent disorders, Cushing’s disease is observed more frequently.
Investigations that are useful for the diagnosis of Cushing’s syndrome include
measurement of 24-hour urinary free cortisol (values are elevated in Cushing’s
syndrome), loss of circadian rhythm (measurement of cortisol at 9 AM and
midnight should show loss of circadian rhythm as evidenced by higher midnight
cortisol values compared to 9 AM values in patients with Cushing’s syndrome), an
overnight dexamethasone suppression test (patients take 1 mg of dexamethasone
at bedtime and serum cortisol is measured the following morning; Cushing
syndrome patients should still show elevated levels of cortisol), as well as lowand high-dose dexamethasone suppression tests.
Pseudo-Cushing’s syndrome is caused by conditions such as alcoholism, severe
obesity, polycystic ovary syndrome, etc.; these can activate the
hypothalamicÀpituitaryÀadrenal axis and cause Cushing’s-like syndrome.
Conn’s syndrome is most often due to an adenoma secreting aldosterone from the
adrenal cortex. Clinical symptoms include hypertension (due to sodium and water
retention) and hypokalemia. Therefore, it is imperative to measure serum
electrolytes in a hypertensive patient if there is any suspicion of secondary
hypertension. Other tests that may be helpful for diagnosis of Conn’s syndrome
include aldosterone-to-renin ratio (ARR; increased in Conn’s syndrome), plasma
potassium and urinary potassium tests (in Conn’s syndrome hypokalemia in serum
and increased loss of potassium in urine is observed), and a saline suppression
test (aldosterone levels are measured before and after administration of normal
saline). Normal individuals should have lower aldosterone levels with the influx of
sodium, but in patients with Conn’s syndrome aldosterone levels may not change.
Renin levels are also low in Conn’s syndrome.
Adrenal insufficiency can be primary, secondary, or tertiary. Primary adrenal
insufficiency (hypoadrenalism) can be either acute or chronic. Primary acute
hypoadrenalism is most commonly due to hemorrhagic destruction of adrenal
glands (WaterhouseÀFriderichsen syndrome). Chronic hypoadrenalism is
Addison’s disease, where there is progressive dysfunction of adrenal glands a local
disease process or systematic disorder. Secondary hypoadrenalism is due to lack
of ACTH from the pituitary because of hypothalamusÀpituitary dysfunction.
Tertiary hypoadrenalism is due to lack of corticotropin-releasing hormone (CRH).
Causes of Addison’s disease include congenital adrenal hyperplasia due to
enzyme defect, autoimmune disease, post-surgery complications, tuberculosis,
Hypogonadism may be broadly divided into two categories: hypergonadotropic
and hypogonadotropic hypogonadism. Examples of hypergonadotropic
hypogonadism include gonadal agenesis, gonadal dysgenesis (e.g. Turner’s
syndrome and Klinefelter’s syndrome), steroidogenesis defect, gonadal failure
(e.g. mumps, radiation, chemotherapy, autoimmune diseases, granulomatous
diseases), and chronic diseases (e.g. liver failure, renal failure).
Examples of hypogonadotropic hypogonadism include hypothalamic lesions (e.g.
tumors, infections, Kallmann’s syndrome) and pituitary lesions (e.g. adenomas,
Sheehan’s syndrome, sarcoidosis, hemochromatosis).
Gastrinomas cause increased secretion of gastric acid, which results in multiple
recurrent duodenal ulcers (ZollingerÀEllison syndrome). VIPomas produce
excessive vasoactive intestinal polypeptides (VIP) that cause watery diarrhea
(VernerÀMorrison syndrome). Glucagonomas are rare tumors from the alpha islet
cells. Features include diabetes mellitus, migratory necrolytic dermatitis, and deep
vein thrombosis. Somatostatinomas are rare tumors derived from the delta islet
cells. Features include diabetes mellitus and gallstones. This condition is caused
by the occurrence of simultaneous or metachronous tumors that involve multiple
endocrine glands. The subtypes are MEN type 1 (parathyroid adenoma or
hyperplasia with pituitary adenoma and pancreatic islet cell tumor), MEN type 2a
(adrenal tumor with medullary carcinoma of thyroid and parathyroid hyperplasia),
and MEN type 2b (type 2a with marfanoid habitus, intestinal, and visceral
Glucose tolerance test is useful in the diagnosis of hyperpituitarism.
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For diagnosis of hypopituitarism, a bolus test (also known as dynamic pituitary
function test) is used where three hormones, including insulin, GnRH, and TRH
are injected as a bolus into a patient’s vein to stimulate the anterior pituitary
gland. Before bolus injection, baseline levels of cortisol, GH, prolactin, TSH, LH,
and FSH are measured. After bolus administration, insulin-induced hypoglycemia
should increase levels of cortisol and GH, while TRH should increase levels of TSH
and prolactin; finally, levels of LH and FSH should be increased due to
administration of GnRH. Serum glucose value is also measured to ensure
hypoglycemia induced by insulin. In a patient with hypopituitarism, levels of these
hormones should stay low at baseline values despite administration of these
hormones by bolus injection.
In patients with Cushing’s syndrome, no suppression of cortisol level is observed
following administration of dexamethasone.
High-dose dexamethasone suppression test is useful to differentiate Cushing’s
syndrome caused by adrenal tumors and non-endocrine ACTH-secreting tumors
from Cushing’s disease.
Although the glucose tolerance test is sometimes considered the gold standard for
evaluating hypothalamusÀpituitaryÀadrenal function in adrenal insufficiency, the
ACTH-stimulation test (i.e. the cosyntropin test) is also used to evaluate the
functional capacity of adrenal glands in a patient with suspected adrenal
insufficiency. Sometimes the long-acting ACTH-stimulation test using 1 mg of
synthetic ACTH is used for differentiation between primary and secondary
hypoadrenalism. In primary hypoadrenalism there will be no rise in serum cortisol.
However, in secondary hypoadrenalism there will be a gradual increase in serum
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Liver Diseases and Liver Function Tests
10.1 LIVER PHYSIOLOGY
The liver is the largest internal organ of the body, approximately 1.2 to 1.5 kg
in weight. The liver performs multiple functions essential to sustaining life
and is the principal site for synthesis of all circulating proteins, except gamma
globulins. A functioning normal liver produces 10À12 g of albumin daily; the
half-life of albumin is approximately 3 weeks. When liver function is impaired
over a prolonged period, albumin synthesis is severely impaired.
Hypoalbuminemia is commonly found in chronic liver disease. However, a
significant reduction in serum albumin levels may not be observed in patients
with acute liver failure. In addition to albumin, all clotting factors (with the
exception of Factor VIII) are produced in the liver. Therefore, as expected
when liver function is significantly impaired, there is reduced production of
clotting factors by the liver. As a result, coagulation tests such as prothrombin
time (PT) is prolonged. Liver is also the site of urea production. In severe liver
disease, such as fulminant hepatic failure, urea levels may be low. The liver
also stores about 80 g of glycogen. Liver releases glucose into the circulation
by glycogenolysis and gluconeogenesis. Again, in severe liver disease, hypoglycemia may be apparent due to depletion of the glycogen supply. Therefore,
common features of significant liver dysfunction include:
Prolonged PT, low serum glucose, and urea.
Severe hypoalbuminemia, a common feature of chronic liver disease.
The liver also plays a major role in the synthesis of various lipoproteins, including very low density lipoprotein (VLDL) and high density lipoprotein (HDL).
Hepatic lipase removes triglycerides from intermediate density lipoprotein
(IDL) to produce low density lipoprotein (LDL). Liver is also a site for cholesterol synthesis. Cholesterol is esterified with fatty acids by the action of enzyme
lecithin cholesterol acyl transferase (LCAT). In liver disease LCAT activity may
be reduced, resulting in an increased ratio of cholesterol to cholesteryl ester.
10.2 Liver Function
10.3 Jaundice: An
Introduction ............. 182
Hyperbilirubinemia . 182
Jaundice ................... 184
Jaundice ................... 185
10.7 Chronic Liver
Disease ..................... 185
Jaundice ................... 187
10.9 Alcohol- and
Disease ..................... 188
10.10 Liver Disease
in Pregnancy............ 188
10.11 Liver Disease in
10.12 Macro Liver
A. Dasgupta and A. Wahed: Clinical Chemistry, Immunology and Laboratory Quality Control
© 2014 Elsevier Inc. All rights reserved.
C H A P T E R 1 0:
L i v er D i s e a s e s an d L i v e r Fu n c t i o n T e s t s
Bilirubin and Other
Tests ......................... 190
Key Points ................ 191
References ............... 195
This may alter membrane structure with formation of target cells, as seen in liver
disease. Bile acids are also synthesized in the liver from cholesterol and are
excreted as bile salts. The primary bile acids (cholic acid and chenodeoxycholic
acid) are converted into secondary bile acids by bacterial enzymes in the intestine. The secondary bile acids are deoxycholic and lithocholic acid. In liver diseases decreased production of bile acids may result in fat malabsorption.
Liver is the site of bilirubin metabolism. Heme, derived from the breakdown
of hemoglobin, is converted to biliverdin and finally into bilirubin, which is
water-soluble, unconjugated bilirubin. Unconjugated bilirubin can also bind
with serum proteins, most commonly albumin. Unconjugated bilirubin is
taken up by the liver, and, with the help of the enzyme UDP (uridine-50 diphosphate) glucuronyl transferase, is converted to conjugated bilirubin
(bilirubin conjugated with glucuronide). This conjugation takes place in the
smooth endoplasmic reticulum of the hepatocyte. Conjugated bilirubin is
water-soluble and is excreted in bile. In the clinical laboratory, conjugated
bilirubin is measured as direct bilirubin, while subtracting total bilirubin
from the direct bilirubin value provides the concentration of unconjugated
bilirubin (also referred to as indirect bilirubin). In the intestine, bacterial
enzymes hydrolyze conjugated bilirubin and release free bilirubin, which is
reduced to urobilinogen. Urobilinogen bound to albumin is excreted in the
urine. Some urobilinogen is converted to stercobilinogen in the intestine and
is excreted in stool. Thus, in normal urine, only urobilinogen is present and
in normal stool stercobilinogen is present. In obstructive (cholestatic) jaundice conjugated bilirubin regurgitates into the blood, and, because it is
water-soluble, it is excreted into the urine. This is called choluria, or the presence of bile in urine. In obstructive jaundice, less conjugated bilirubin is
taken by the intestine and as a result less stercobilinogen is found in the
stool (pale stools). Normal individuals have mostly unconjugated bilirubin
in their blood, urobilinogen in their urine, and stercobilinogen in their stool.
The distribution of bilirubin, urobilinogen, and stercobilinogen in various
diseases are summarized below:
In individuals with hemolytic anemia, the excess breakdown of
hemoglobin causes unconjugated hyperbilirubinemia. Urobilinogen in
urine and stercobilinogen in stool may also be increased.
In hepatocellular jaundice, uptake and conversion of unconjugated
bilirubin into conjugated bilirubin is also reduced, resulting in
unconjugated hyperbilirubinemia. However, amounts of urobilinogen in
urine and stercobilinogen in stool are not increased.
In cholestatic jaundice, conjugated hyperbilirubinemia is usually
observed. Because conjugated bilirubin is water-soluble, it is excreted in
urine (choluria). However, urobilinogen and stercobilinogen quantities