GIT Endocrine Tricky Questions

Release of which of the following peptides leads to an increase in the secretion of pancreatic enzymes into the
small intestine?


A. Cholecystokinin

B. Gastrin

C. Motilin

D. Secretin

E. Somatostatin


Explanation:

The correct answer A. Release of cholecystokinin is stimulated by the presence of peptides, amino acids, or
fatty acids in the small intestine. Cholecystokinin acts on the pancreas to stimulate secretion of pancreatic
enzymes that aid in the digestion of these compounds.

Gastrin (choice B) secretion is stimulated by the presence of peptides or amino acids in the lumen of the
stomach, and produces an increase in gastric H+ secretion.

Motilin (choice C) is a hormone that regulates the migrating myoelectric complex, a series of contractions that
occur during fasting, clearing the stomach and small intestine of any residual food.

Secretin (choice D) secretion is stimulated by the presence of H+ and fatty acids in the duodenum, and causes
an increase in pancreatic and biliary HCO3– release and a decrease in gastric H+ release.

Somatostatin (choice E) secretion is stimulated by the presence of H+ in the lumen, and results in decreased
release of all gastrointestinal hormones and decreased H+ secretion in the stomach.



A 42-year-old obese woman experiences episodic abdominal pain. She notes that the pain increases after the
ingestion of a fatty meal. The action of which of the following hormones is responsible for the postprandial
intensification of her symptoms?


A. Cholecystokinin

B. Gastrin

C. Pepsin

D. Secretin

E. Somatostatin


Explanation:

The correct answer is A. This woman has a risk profile (female, fat, forties) and symptomatology consistent with
gallstones (cholelithiasis). As would be expected, contraction of the gallbladder following a fatty meal often
exacerbates the pain caused by gallstones. Cholecystokinin (CCK), the release of which is stimulated by dietary
fat, is the hormone responsible for stimulation of gallbladder contraction. It is produced in I cells of the
duodenum and jejunum. In addition to gallbladder contraction, CCK also stimulates pancreatic enzyme secretion
and decreases the rate of gastric emptying.

Gastrin (choice B) is produced by the G cells of the antrum and duodenum. Gastrin stimulates the secretion of
HCl from the parietal cells and pepsinogen from the chief cells of the stomach. Gastrin secretion is stimulated by
gastric distention, digestive products (e.g., amino acids), and vagal discharge.

Pepsin (choice C) is a protease produced by the chief cells of the stomach (as pepsinogen). It is involved in the
digestion of proteins. Pepsinogen release is stimulated by vagal stimulation, gastrin, local acid production,
secretin, CCK, and histamine.

Secretin (choice D) is produced by the S cells of the duodenum. It is secreted primarily in response to
acidification of the duodenal mucosa. Secretin stimulates the secretion of bicarbonate-containing fluid from the
pancreas and biliary ducts. This neutralization allows pancreatic enzymes to function. Secretin also inhibits
gastric acid production and gastric emptying.

Somatostatin (choice E) is produced by the D cells of the pancreatic islets and in the gastric and intestinal
mucosa. Somatostatin is an inhibitory hormone—it inhibits most gastrointestinal hormones, gallbladder
contraction, gastric acid and pepsinogen secretion, pancreatic and small intestinal fluid secretion, and both
glucagon and insulin release.



A young boy presents with failure to thrive. Biochemical analysis of a duodenal aspirate after a meal reveals a
deficiency of enteropeptidase (enterokinase). The levels of which of the following digestive enzymes would be
affected?


A. Amylase

B. Colipase

C. Lactase

D. Pepsin

E. Trypsin


Explanation:

The correct answer is E. Enteropeptidase, formerly called enterokinase, activates trypsinogen by limited
proteolytic digestion to give trypsin. Trypsin is itself capable of activating trypsinogen, which produces a positive
feedback effect. Trypsin also activates chymotrypsinogen (and several other proteolytic enzymes), so
deficiency of enteropeptidase results in a severe deficiency of enzymes that digest protein.

Amylase (choice A) aids in the breakdown of starches to oligosaccharides, maltose, and maltotriose.

Colipase (choice B), along with other lipases, functions to digest fats.

Lactase (choice C) is a brush-border disaccharidase that hydrolyzes the bond between galactose and glucose
in lactose.

Pepsin (choice D) is a proteolytic enzyme secreted in an inactive form (pepsinogen) by the chief cells of the
stomach. Pepsinogen is activated by stomach acid, and so is not dependent on enteropeptidase. Pepsin alone
will not replace the activities of other proteolytic enzymes, partly because food does not remain in the stomach
for an extended period of time.



A 70-year-old woman undergoes a gastrectomy for Zollinger-Ellison syndrome. Her doctor informs her that she
will need to take intramuscular vitamin B12 shots for the rest of her life. Absence of which of the following cell
types is responsible for this vitamin replacement requirement?


A. Chief cells

B. G cells

C. Goblet cells

D. Mucous neck cells

E. Parietal cells


Explanation:

The correct answer is E. The parietal cells of the stomach produce intrinsic factor, a glycoprotein that binds
vitamin B12 in the lumen of the stomach and facilitates its absorption in the terminal ileum. Patients without a
stomach and those with pernicious anemia (autoimmune destruction of parietal cells) will require B12
replacement therapy. Recall that B12 deficiency will lead to megaloblastic anemia and the USMLE-favorite
picture of a blood smear with hypersegmented neutrophils. Note that parietal cells also synthesize and secrete
HCl.

Chief cells (choice A) are responsible for secreting pepsinogen, the precursor to pepsin.

G cells (choice B) are gastrin-secreting cells. Gastrin stimulates secretion of acid by the parietal cells found in
the body and fundus of the stomach. Zollinger-Ellison syndrome is caused by a pancreatic or duodenal tumor
that secretes gastrin (a gastrinoma). It is characterized by the development of severe peptic ulcer disease.

Goblet cells (choice C) are part of the mucosa of the small intestine, not the stomach. They produce
glycoproteins (mucins) that protect and lubricate the lining of the intestine.

Mucous neck cells (choice D) are mucus-secreting cells located in the necks of the gastric glands.



During a fast, a brief phase of intense sequential contractions begins in the stomach and gradually migrates to
the ileum. Release of which of the following intestinal hormones is most likely responsible for this observed
effect?


A. Cholecystokinin

B. Gastrin

C. Gastrin-releasing peptide

D. Motilin

E. Secretin

F. Somatostatin


Explanation:

The correct answer is D. Motilin is a hormone released by the small intestine during the fasting state. Its waxing
and waning blood levels correlate with the initiation and ending of migrating motor complexes (MMC).
Furthermore, injection of motilin has been shown to evoke MMC activity. The MMC typically begins in the
stomach, and over a 90-120 minute period, migrates to the ileum, where it dies out. As one complex dies out in
the ileum, another complex begins in the stomach provided the fasting state continues. Eating a meal interrupts
the MMC activity.

Cholecystokinin (choice A) is released during the intestinal phase of the digestive period (not during a fast). Its
secretion is evoked by the presence of fat and protein digestion products in the duodenum. It induces
contraction of the gall bladder and relaxation of the sphincter of Oddi.

Gastrin (choice B) is released from G cells in the antrum, mostly during the gastric phase of the digestive period
(not during a fast). It tends to increase stomach motility, although the rate of emptying is decreased because
gastrin also causes the pyloric sphincter to contract. It also may contribute to the increase in ileal and colonic
motility as part of the gastroileal and gastrocolic reflexes, respectively.

Gastrin-releasing peptide (choice C) mediates the neural release of gastrin. Antral enteric neurons that are
activated by vagal efferents or by local reflexes release gastrin-releasing peptide, which stimulates the G cells
to secrete gastrin.

Secretin (choice E) is a duodenal hormone that is released during the intestinal phase of the digestive period
(not during a fast). Its secretion is evoked by a duodenal pH less than 4.5. Secretin tends to decrease the rate
of stomach emptying.

Somatostatin (choice F) is released by delta cells in the stomach mucosa. It mediates the inhibition of gastrin
secretion that occurs when the pH of the gastric juice falls below 3. It also acts directly on the parietal cell to
decrease acid secretion.



A patient undergoes a total gastrectomy because of a proximally located gastric cancer. After the surgery, which
of the following digestive enzymes will be produced in inadequate amounts?


A. Amylase

B. Chymotrypsin

C. Lipase

D. Pepsin

E. Trypsin


Explanation:

The correct answer is D. Pepsin is secreted (in an inactive or zymogen form as pepsinogen) by the chief cells of
the stomach. Pepsinogen is activated by contact with stomach acid. Although protein digestion usually begins
with the actions of hydrochloric acid and pepsin, pancreatic enzymes complete the job as the food passes into
the small intestine.

Amylases (choice A) hydrolyze 1->4 glycosidic linkages of starches to produce oligosaccharides, maltose,
maltotriose, and limit dextrins. These enzymes are produced by the pancreas and salivary glands.

Chymotrypsin (choice B) is a proteolytic enzyme released by the pancreas as the inactive proenzyme,
chymotrypsinogen.

Lipases (choice C) are mostly released by the pancreas, and serve to digest various lipids, including
triacylglycerols.

Trypsin (choice E) is a proteolytic enzyme released by the pancreas as the inactive proenzyme, trypsinogen.



During a fast, a brief phase of intense sequential contractions begins in the stomach and gradually migrates to
the ileum. Release of which of the following intestinal hormones is most likely responsible for this observed
effect?


A. Cholecystokinin

B. Gastrin

C. Gastrin-releasing peptide

D. Motilin

E. Secretin

F. Somatostatin


Explanation:

The correct answer is D. Motilin is a hormone released by the small intestine during the fasting state. Its waxing
and waning blood levels correlate with the initiation and ending of migrating motor complexes (MMC).
Furthermore, injection of motilin has been shown to evoke MMC activity. The MMC typically begins in the
stomach, and over a 90-120 minute period, migrates to the ileum, where it dies out. As one complex dies out in
the ileum, another complex begins in the stomach provided the fasting state continues. Eating a meal interrupts
the MMC activity.

Cholecystokinin (choice A) is released during the intestinal phase of the digestive period (not during a fast). Its
secretion is evoked by the presence of fat and protein digestion products in the duodenum. It induces
contraction of the gall bladder and relaxation of the sphincter of Oddi.

Gastrin (choice B) is released from G cells in the antrum, mostly during the gastric phase of the digestive period
(not during a fast). It tends to increase stomach motility, although the rate of emptying is decreased because
gastrin also causes the pyloric sphincter to contract. It also may contribute to the increase in ileal and colonic
motility as part of the gastroileal and gastrocolic reflexes, respectively.

Gastrin-releasing peptide (choice C) mediates the neural release of gastrin. Antral enteric neurons that are
activated by vagal efferents or by local reflexes release gastrin-releasing peptide, which stimulates the G cells
to secrete gastrin.

Secretin (choice E) is a duodenal hormone that is released during the intestinal phase of the digestive period
(not during a fast). Its secretion is evoked by a duodenal pH less than 4.5. Secretin tends to decrease the rate
of stomach emptying.

Somatostatin (choice F) is released by delta cells in the stomach mucosa. It mediates the inhibition of gastrin
secretion that occurs when the pH of the gastric juice falls below 3. It also acts directly on the parietal cell to
decrease acid secretion.
A 70-year-old woman undergoes a gastrectomy for Zollinger-Ellison syndrome. Her doctor informs her that she
will need to take intramuscular vitamin B12 shots for the rest of her life. Absence of which of the following cell
types is responsible for this vitamin replacement requirement?


A. Chief cells

B. G cells

C. Goblet cells

D. Mucous neck cells

E. Parietal cells


Explanation:

The correct answer is E. The parietal cells of the stomach produce intrinsic factor, a glycoprotein that binds
vitamin B12 in the lumen of the stomach and facilitates its absorption in the terminal ileum. Patients without a
stomach and those with pernicious anemia (autoimmune destruction of parietal cells) will require B12
replacement therapy. Recall that B12 deficiency will lead to megaloblastic anemia and the USMLE-favorite
picture of a blood smear with hypersegmented neutrophils. Note that parietal cells also synthesize and secrete
HCl.

Chief cells (choice A) are responsible for secreting pepsinogen, the precursor to pepsin.

G cells (choice B) are gastrin-secreting cells. Gastrin stimulates secretion of acid by the parietal cells found in
the body and fundus of the stomach. Zollinger-Ellison syndrome is caused by a pancreatic or duodenal tumor
that secretes gastrin (a gastrinoma). It is characterized by the development of severe peptic ulcer disease.

Goblet cells (choice C) are part of the mucosa of the small intestine, not the stomach. They produce
glycoproteins (mucins) that protect and lubricate the lining of the intestine.

Mucous neck cells (choice D) are mucus-secreting cells located in the necks of the gastric glands.


A patient undergoes a total gastrectomy because of a proximally located gastric cancer. After the surgery, which
of the following digestive enzymes will be produced in inadequate amounts?


A. Amylase

B. Chymotrypsin

C. Lipase

D. Pepsin

E. Trypsin


Explanation:

The correct answer is D. Pepsin is secreted (in an inactive or zymogen form as pepsinogen) by the chief cells of
the stomach. Pepsinogen is activated by contact with stomach acid. Although protein digestion usually begins
with the actions of hydrochloric acid and pepsin, pancreatic enzymes complete the job as the food passes into
the small intestine.

Amylases (choice A) hydrolyze 1->4 glycosidic linkages of starches to produce oligosaccharides, maltose,
maltotriose, and limit dextrins. These enzymes are produced by the pancreas and salivary glands.

Chymotrypsin (choice B) is a proteolytic enzyme released by the pancreas as the inactive proenzyme,
chymotrypsinogen.

Lipases (choice C) are mostly released by the pancreas, and serve to digest various lipids, including
triacylglycerols.

Trypsin (choice E) is a proteolytic enzyme released by the pancreas as the inactive proenzyme, trypsinogen.





A 42-year-old obese woman experiences episodic abdominal pain. She notes that the pain increases after the
ingestion of a fatty meal. The action of which of the following hormones is responsible for the postprandial
intensification of her symptoms?


A. Cholecystokinin

B. Gastrin

C. Pepsin

D. Secretin

E. Somatostatin


Explanation:

The correct answer is A. This woman has a risk profile (female, fat, forties) and symptomatology consistent with
gallstones (cholelithiasis). As would be expected, contraction of the gallbladder following a fatty meal often
exacerbates the pain caused by gallstones. Cholecystokinin (CCK), the release of which is stimulated by dietary
fat, is the hormone responsible for stimulation of gallbladder contraction. It is produced in I cells of the
duodenum and jejunum. In addition to gallbladder contraction, CCK also stimulates pancreatic enzyme secretion
and decreases the rate of gastric emptying.

Gastrin (choice B) is produced by the G cells of the antrum and duodenum. Gastrin stimulates the secretion of
HCl from the parietal cells and pepsinogen from the chief cells of the stomach. Gastrin secretion is stimulated by
gastric distention, digestive products (e.g., amino acids), and vagal discharge.

Pepsin (choice C) is a protease produced by the chief cells of the stomach (as pepsinogen). It is involved in the
digestion of proteins. Pepsinogen release is stimulated by vagal stimulation, gastrin, local acid production,
secretin, CCK, and histamine.

Secretin (choice D) is produced by the S cells of the duodenum. It is secreted primarily in response to
acidification of the duodenal mucosa. Secretin stimulates the secretion of bicarbonate-containing fluid from the
pancreas and biliary ducts. This neutralization allows pancreatic enzymes to function. Secretin also inhibits
gastric acid production and gastric emptying.

Somatostatin (choice E) is produced by the D cells of the pancreatic islets and in the gastric and intestinal
mucosa. Somatostatin is an inhibitory hormone—it inhibits most gastrointestinal hormones, gallbladder
contraction, gastric acid and pepsinogen secretion, pancreatic and small intestinal fluid secretion, and both
glucagon and insulin release.




Release of which of the following peptides leads to an increase in the secretion of pancreatic enzymes into the
small intestine?


A. Cholecystokinin

B. Gastrin

C. Motilin

D. Secretin

E. Somatostatin


Explanation:

The correct answer A. Release of cholecystokinin is stimulated by the presence of peptides, amino acids, or
fatty acids in the small intestine. Cholecystokinin acts on the pancreas to stimulate secretion of pancreatic
enzymes that aid in the digestion of these compounds.

Gastrin (choice B) secretion is stimulated by the presence of peptides or amino acids in the lumen of the
stomach, and produces an increase in gastric H+ secretion.

Motilin (choice C) is a hormone that regulates the migrating myoelectric complex, a series of contractions that
occur during fasting, clearing the stomach and small intestine of any residual food.

Secretin (choice D) secretion is stimulated by the presence of H+ and fatty acids in the duodenum, and causes
an increase in pancreatic and biliary HCO3– release and a decrease in gastric H+ release.

Somatostatin (choice E) secretion is stimulated by the presence of H+ in the lumen, and results in decreased
release of all gastrointestinal hormones and decreased H+ secretion in the stomach.



A young boy presents with failure to thrive. Biochemical analysis of a duodenal aspirate after a meal reveals a
deficiency of enteropeptidase (enterokinase). The levels of which of the following digestive enzymes would be
affected?


A. Amylase

B. Colipase

C. Lactase

D. Pepsin

E. Trypsin


Explanation:

The correct answer is E. Enteropeptidase, formerly called enterokinase, activates trypsinogen by limited
proteolytic digestion to give trypsin. Trypsin is itself capable of activating trypsinogen, which produces a positive
feedback effect. Trypsin also activates chymotrypsinogen (and several other proteolytic enzymes), so
deficiency of enteropeptidase results in a severe deficiency of enzymes that digest protein.

Amylase (choice A) aids in the breakdown of starches to oligosaccharides, maltose, and maltotriose.

Colipase (choice B), along with other lipases, functions to digest fats.

Lactase (choice C) is a brush-border disaccharidase that hydrolyzes the bond between galactose and glucose
in lactose.

Pepsin (choice D) is a proteolytic enzyme secreted in an inactive form (pepsinogen) by the chief cells of the
stomach. Pepsinogen is activated by stomach acid, and so is not dependent on enteropeptidase. Pepsin alone
will not replace the activities of other proteolytic enzymes, partly because food does not remain in the stomach
for an extended period of time.


A pregnant woman in her second trimester complains of heat intolerance and palpitations. Physical examination
reveals a slightly enlarged, non-tender thyroid gland, and a normal cardiac exam. The serum thyroxine (T4) level
is increased; however, the serum thyroid-stimulating hormone (TSH) is normal. Which of the following best
explains the laboratory findings in this patient?


A. Decreased estrogen

B. Increased free thyroxine (T4)

C. Increased progesterone

D. Increased serum triiodothyronine (T3)

E. Increased thyroid-binding globulin (TBG)


Explanation:

The correct answer is E. The total serum thyroxine (T4) represents the sum of the T4 bound to thyroid-binding
globulin (TBG) and the free T4. An increased total T4 may be due to an increase in TBG or an increase in free
T4, the latter leading to signs of thyrotoxicosis. A decreased total T4 may be secondary to a reduction in TBG
or in free T4, the latter leading to signs of hypothyroidism.

In a euthyroid state, one-third of the binding sites on TBG are occupied by T4. An increase in estrogen
(pregnancy, birth control pills) increases the synthesis of TBG. Since one-third of the binding sites on TBG will
be occupied, the T4 bound to the additional TBG increases the total serum T4. The addition of extra TBG does
not alter the free T4 level because of the equilibrium between the serum concentration of T4 and thyroid gland
T4 production. Since the free T4 level is normal, there is no stimulus to release thyroid-stimulating hormone
(TSH) from the pituitary gland. Regarding the patient's enlarged thyroid gland, heat intolerance, and
palpitations, these are normal findings in pregnancy and do not indicate an overactive thyroid gland.

Estrogen is increased (not decreased) in pregnancy (choice A).

The serum free T4 (choice B) is normal in pregnancy. This explains why the serum TSH is normal in the
presence of an elevated serum T4, which reflects the increase in TBG normally occurring in pregnancy.

The increase in progesterone (choice C) during pregnancy has no effect on TBG levels.

Although the serum T3 (choice D) concentration is increased in pregnancy for the same reason as serum T4
(more T3 is bound to TBG), it is not responsible for the increase in synthesis of TBG that leads to the increase
in serum T4.



An asymptomatic, 24-year-old African-American woman in her second trimester of pregnancy has the following
laboratory findings:

Based on the laboratory data,
which of the following tests is necessary for further evaluation of this patient?
LAB VALUES

A. Creatinine clearance

B. Oral glucose tolerance test

C. Serum ferritin

D. Sickle cell preparation

E. No further study is necessary


Explanation:

The correct answer is E. All of the laboratory data in this pregnant woman are normal, hence no further study is
necessary. In a normal pregnancy, both the plasma volume and RBC mass are increased with a greater increase in
the plasma volume than RBC mass (2:1 ratio). This has a dilutional effect on many laboratory tests.

Increasing plasma volume in pregnancy increases the creatinine clearance (choice A) due to the expected elevation
in the glomerular filtration rate (GFR). The reference intervals for serum blood urea nitrogen and creatinine are lower
than normal, due to the dilutional effect of increased plasma volume and increased clearance of both analytes in the
urine caused by the rise in the GFR.

The threshold for glucose is reduced in pregnancy, so patients can have a positive dipstick test for glucose in the
presence of a normal serum glucose. Therefore, an oral glucose tolerance test (choice B) is not indicated.

The hemoglobin (Hb) concentration in pregnancy is normally decreased because of the dilutional effect of increased
plasma volume. Since the Hb is normal (for a pregnant woman) in this patient, a serum ferritin (choice C) to rule out
iron deficiency is unnecessary. Furthermore, iron deficiency is usually associated with a low MCV (microcytic anemia),
and her MCV is normal.

Although sickle disease is the most common genetic hemoglobinopathy among African Americans, the patient is not
anemic, so there is no reason to order a sickle cell preparation (choice D).





Two normal, healthy subjects volunteer for a study on insulin secretion. In Patient 1, blood glucose is increased
to 150 mg/dL by direct intravenous infusion. In Patient 2, blood glucose is increased to 150 mg/dL by ingestion of
oral glucose. The peak plasma insulin concentration produced in Patient 1 is 70 µU/mL while in Patient 2, it is 95
µU/mL. Which of the following best explains the higher insulin concentration in Patient 2?


A. Ingested glucose activates a sympathetic reflex that increases β cell release of insulin

B. Ingested glucose increases duodenal secretion of gastric inhibitory peptide (GIP),
increasing β cell release of insulin

C. Intravenous glucose increases islet cell secretion of somatostatin, inhibiting β cell release of
insulin

D. Intravenous glucose increases islet cell secretion of glucagon, inhibiting β cell release of insulin


Explanation:

The correct answer is B. Ingestion of glucose results in secretion of a "gut factor" into the blood that
subsequently increases insulin secretion by β cells. The most likely candidate for this action is the
intestinal peptide known as gastric inhibitory peptide (GIP), which obviously was named for its effects on the
stomach. GIP secretion is increased during ingestion of glucose and the blood level produced is sufficient to
stimulate insulin secretion. Because of this effect on insulin secretion, GIP is sometimes referred to as
glucose-dependent insulinotropic peptide.

Activation of the sympathetic innervation to the pancreas inhibits insulin secretion via an α2-adrenergic
mechanism. Hence, any sympathetic reflexes activated during ingestion of glucose would decrease (not
increase, choice A) insulin secretion.

While paracrine release of somatostatin (choice C) by Δ cells in the islets does inhibit insulin secretion by
β cells, there is no reason to suspect that intravenous versus ingested glucose would have a differential
effect on somatostatin release. The same holds true for glucagon secretion by α cells. Furthermore,
glucagon has a paracrine effect to increase (not decrease, choice D) insulin secretion.



An XX genotypic infant is born with ambiguous genitalia. Laboratory examination reveals hypoglycemia,
hyperkalemia, and salt wasting. Serum 17-OH progesterone is markedly increased. Which of the following is the
most likely diagnosis?


A. 5-alpha-reductase deficiency

B. 11-beta-hydroxylase deficiency

C. 17-alpha-hydroxylase deficiency

D. 21-hydroxylase deficiency

E. Complete androgen resistance


Explanation:

The correct answer is D. 21-hydroxylase deficiency is the most common form of congenital adrenal hyperplasia.
The simple virilizing variant (without salt wasting) is most common, but with severe 21-hydroxylase deficiency,
virilization and salt wasting occur. The infant described above exhibits salt wasting and hyperkalemia because
aldosterone secretion is diminished by the enzyme deficiency. The hypoglycemia is due to cortisol deficiency.
Because cortisol secretion is diminished in congenital adrenal hyperplasia, ACTH secretion from the anterior
pituitary is increased due to loss of negative feedback inhibition. The high levels of ACTH are responsible for
the adrenal hyperplasia and the increased secretion of the adrenal androgens, dehydroepiandrosterone and
androstenedione, which are responsible for the virilization of the external genitalia. 17-OH progesterone is the
steroid precursor just proximal to 21-hydroxylase and is also increased because of the excessive drive to the
adrenal cortex by ACTH.

5-alpha-reductase deficiency (choice A) in male fetuses will produce normal differentiation of the internal
reproductive tracts, but the external genitalia will be feminized. This is because testosterone needs to be
converted to dihydrotestosterone (by 5-alpha-reductase) in the external genitalia and the prostate for normal
differentiation into the male phenotype.

11-beta-hydroxylase deficiency (choice B) is another form of congenital adrenal hyperplasia. It is characterized
by salt retention due to excessive secretion by the inner zones of the adrenal cortex of the weak
mineralocorticoid, deoxycorticosterone. Again, the excessive drive to the adrenal cortex is due to increased
ACTH resulting from diminished negative feedback suppression by cortisol. The adrenal also secretes excessive
androgens and virilization occurs in female fetuses.

17-alpha-hydroxylase deficiency (choice C) is another from of congenital adrenal hyperplasia that is
accompanied by salt retention. The high levels of ACTH drive the adrenal cortex to secrete increased amounts
of deoxycorticosterone and corticosterone, both of which have weak mineralocorticoid activity. Without the ability
to 17-alpha-hydroxylate progesterone or pregnenolone, steroid-secreting cells cannot produce sex steroids.
When 17-alpha-hydroxylase deficiency is present in the adrenal cortex, it is also present in the gonads. Hence,
whether it occurs in a male or female fetus, sex steroid production will be diminished. Female fetuses will
develop normal reproductive tracts and genitalia since these structures are programmed in utero to
"automatically" become female. Male fetuses, however, will have their reproductive tracts and genitalia
feminized.

Complete androgen resistance (choice E) results in feminization of affected male fetuses. It is characterized by
an XY genotypic male with phenotypically female external genitalia and a vagina that ends as a blind sac.



Most of the testosterone secreted by the testes exists in the plasma in the form of


A. dihydrotestosterone bound to gonadal steroid-binding hormone

B. free dihydrotestosterone

C. free testosterone

D. testosterone bound to albumin

E. testosterone bound to sex-steroid-binding globulin


Explanation:

The correct answer is E. The majority of circulating testosterone is bound to plasma protein (around 98%),
rather than existing in free form (choice C). Of this, a majority is bound to a specific sex (or gonadal)
steroid-binding protein (choice E), and a minority is bound to albumin (choice D). Dihydrotestosterone is
produced from testosterone in the tissues by a specific enzyme, 5-alpha-reductase, rather than circulating in
bound (choice A) or free (choice B) form.


Which of the following directly inhibits insulin secretion?


A. Alpha2-adrenergic agonist

B. Beta2-adrenergic agonist

C. Cholecystokinin

D. Glucagon

E. Ingestion of a high-sugar meal

F. Muscarinic agonists


Explanation:

The correct answer is A. Alpha2-receptor agonists directly inhibit pancreatic insulin secretion.

Beta2-adrenergic agonists (choice B) stimulate insulin secretion.

Cholecystokinin (choice C) is a hormone that not only causes gallbladder contraction, but also causes insulin
secretion from the pancreas.

Pancreatic glucagon (choice D) release acts as a paracrine stimulus for insulin secretion.

Ingestion of high-sugar meals (choice E) is a stimulus for the secretion of insulin from the pancreas.

Muscarinic activity (choice F) in the GI tract enhances secretion of insulin from the pancreas.



Endometrial biopsy demonstrates a thick endometrium with long, coiled glands lined by a columnar epithelium
with prominent cytoplasmic vacuoles adjacent to the gland lumen. Earlier in the menstrual cycle, the glands were
much smaller and were lined with cells that did not have vacuoles. Which of the following hormones is primarily
responsible for inducing this change in appearance?


A. Aldosterone

B. Cortisol

C. Estrogen

D. Progesterone

E. Thyroxine


Explanation:

The correct answer is D. The endometrial phase with small glands is the proliferative phase; the one with large
glands with secretory cells is the secretory phase. Estrogen (choice C) is necessary for both phases, but it is
the addition of progesterone (choice D), secreted by the corpus luteum after the Graafian follicle ruptures, that
triggers the switch from proliferative to secretory endometrium.

Glucocorticoids (choice B) and the mineralocorticoid aldosterone (choice A) are secreted by the adrenal
glands. They do not produce the endometrial changes described.

Thyroxine (choice E) is secreted by the thyroid gland, and is unrelated to the observed morphologic changes in
the endometrium.



A 55-year-old woman stopped menstruating approximately 3 months ago. Worried that she may be pregnant, she
decided to have a pregnancy test. The test came back negative. Which of the following series of tests results
would confirm that the woman is postmenopausal?


A. Decreased LH, decreased FSH, increased estrogen

B. Decreased LH, increased FSH, decreased estrogen

C. Increased LH, decreased FSH, decreased estrogen

D. Increased LH, increased FSH, decreased estrogen

E. Increased LH, increased FSH, increased estrogen


Explanation:

The correct answer is D. During menopause, there is a loss of functioning follicles in the ovaries such that
GnRH-stimulated LH and FSH secretion do not result in normal estrogen secretion. The low estrogen levels
cannot inhibit gonadotropin secretion in a negative-feedback fashion, resulting in very high levels of LH and
FSH.

Choices A, B, C, and E do not accurately describe normal hormonal levels in menopause.




Which of the following hormones is most important in initiating gall bladder contraction?


A. Cholecystokinin (CCK)

B. Gastric inhibitory peptide (GIP)

C. Gastrin

D. Secretin

E. Vasoactive intestinal polypeptide (VIP)


Explanation:

The correct answer is A. Cholecystokinin, or CCK, is synthesized in the duodenal and jejunal mucosa and
stimulates gall bladder contraction and pancreatic enzyme secretion. Other functions include slowing of gastric
emptying, an atrophic effect on the pancreas, and secretion of antral somatostatin, which in turn, decreases
gastric acid secretion.

Gastric inhibitory peptide, or GIP (choice B), stimulates pancreatic insulin secretion at physiologic doses and
inhibits gastric acid secretion and gastric motility at pharmacologic doses.

Gastrin (choice C) prepares the stomach and small intestine for food processing, including stimulating secretion
of HCl, histamine, and pepsinogen. It also increases gastric blood flow, lower esophageal sphincter tone, and
gastric contractions.

Secretin (choice D) stimulates secretion of bicarbonate-containing fluid from the pancreas and biliary ducts.

Vasoactive intestinal polypeptide, or VIP (choice E), relaxes intestinal smooth muscle and stimulates gut
secretion of water and electrolytes.



Maintenance of the corpus luteum during the first trimester of pregnancy is accomplished principally by the
secretion of


A. antidiuretic hormone (ADH)

B. follicle stimulating hormone (FSH)

C. human chorionic gonadotropin (hCG)

D. luteinizing hormone (LH)

E. progesterone


Explanation:

The correct answer is C. The corpus luteum secretes estrogens, progesterone, and relaxin. hCG, secreted by
the syncytiotrophoblast lining the placental villi, maintains the corpus luteum during the first trimester of
pregnancy.

Antidiuretic hormone (vasopressin; choice A) does not play a significant role during pregnancy.

FSH (choice B) acts on granulosa cells to promote the conversion of androstenedione to estradiol.

LH (choice D) acts on theca cells to promote androstenedione secretion.

Progesterone (choice E) is important for maintaining the pregnancy, however, it does not act to maintain the
corpus luteum.


In the transition from a Graafian follicle to a functional corpus luteum, which of the following cellular events
occurs?


A. Granulosa cells begin to express aromatase

B. Granulosa cells begin to express FSH receptors

C. Granulosa cells begin to express LH receptors

D. Theca cells begin to express LH receptors

E. Theca cells begin to express side-chain cleavage enzyme


Explanation:

The correct answer is C. The secretion of estrogen by the developing follicle can best be explained using the
"two cell" hypothesis. Theca cells are stimulated by LH (theca cells express LH receptors prior to formation of
the corpus luteum, choice D) to secrete the androgens androstenedione and testosterone. The androgens then
diffuse into the granulosa cells, where they are aromatized to estrogens. Hence, theca cells express side-chain
cleavage enzyme (first step in steroidogenesis) prior to the formation of the corpus luteum (choice E). FSH
stimulates aromatase activity in the granulosa cells (receptors for FSH and aromatase enzyme are present prior
to the formation of the corpus luteum, choices A and B). The granulosa cells apparently have the ability to
produce steroids (progesterone), but lack 17α-hydroxylase activity and cannot synthesize estrogen
themselves. Only as the follicle approaches ovulation do LH receptors begin to be expressed by the granulosa
cells. Estrogen and FSH probably are responsible for the change. After ovulation, the scar of the follicle
undergoes luteinization. The theca cells decrease 17α-hydroxylase activity and secrete more
progesterone. The granulosa cells decrease aromatase activity and also secrete more progesterone.



Which of the following areas of the adrenal gland would you expect to increase in activity in a patient subjected to
salt restriction?


A. Adrenal medulla

B. Zona fasciculata of the adrenal cortex

C. Zona glomerulosa of the adrenal cortex

D. Zona reticularis of the adrenal cortex


Explanation:

The correct answer is C. This question requires you to equate salt restriction with an increased synthesis of
aldosterone (aldosterone promotes sodium reabsorption) and then to remember that aldosterone is produced in
the zona glomerulosa of the adrenal cortex. The zona glomerulosa is the outermost layer of the adrenal cortex.

The adrenal medulla (choice A) secretes catecholamines.

The zona fasciculata (choice B) is the middle layer of the adrenal cortex. It primarily secretes glucocorticoids.

The zona reticularis (choice D) is the innermost layer of the adrenal cortex. It primarily secretes androgens such
as dehydroepiandrosterone (DHEA).




A series of photographs taken of a middle-aged man over a period of two decades demonstrates gradual
coarsening of facial features and progressive protrusion of the brows. Upon questioning, the patient reports
having to wear larger shoes than he did as a young man. Which of the following pair of hormones regulates the
hormone responsible for these changes?


A. Dopamine and norepinephrine

B. LH and hCG

C. Prolactin and FSH

D. Somatostatin and GHRH

E. TSH and ACTH


Explanation:

The correct answer is D. The disease is acromegaly, which is typically produced by a growth hormone-secreting
pituitary adenoma. Growth hormone synthesis is predominately regulated by hypothalamic GHRH (growth
hormone releasing hormone), and its pulsatile secretion is predominately regulated by hypothalamic
somatostatin.

Dopamine and norepinephrine (choice A) are catecholamines that regulate smooth muscle tone and cardiac
function.

Choice B is incorrect because luteinizing hormone (LH) regulates sex steroid hormone production by both
testes and ovaries; human chorionic gonadotropin (hCG) is produced by the placenta and has actions similar to
LH.

Choice C is incorrect because prolactin regulates menstruation and lactation, while follicle stimulating hormone
(FSH) regulates ovarian and testicular function.

Choice E is incorrect because thyroid stimulating hormone (TSH) regulates secretion of thyroid hormones and
adrenocorticotropin (ACTH) regulates glucocorticoid secretion.



A normal, healthy, 24-year-old woman has regular menstrual cycles, each lasting about 28 days. Daily serum
samples from the woman reveal decreasing progesterone and 17-β-estradiol levels. Serum LH and FSH
levels are low, and begin rising. Basal body temperature begins falling. Within three days, which of the following
events would be expected to occur?


A. Markedly increased inhibin levels

B. Menstruation

C. Ovulation

D. Rapidly decreased LH levels

E. Significantly increased basal body temperature


Explanation:

The correct answer is B. A typical menstrual cycle lasts around 26-30 days. The luteal phase (post-ovulation)
generally lasts fourteen days; the length of the follicular phase (pre-ovulation) is far more variable, and
accounts for most of the variability observed in the length of the menstrual cycle. Just before menstruation, sex
steroid levels are low, but gonadotropin levels (especially FSH) begin rising slightly. Basal body temperature
remains high during the luteal phase of the menstrual cycle, but falls precipitously a few days before the onset
of menstruation.

Markedly increased inhibin levels (choice A) are seen in the middle of the luteal phase, dropping to low levels
just before menstruation.

LH levels peak approximately 36 hours before ovulation (choice C), then decrease rapidly (choice D) within a
few days to a low level during the mid-luteal phase, gradually decreasing until menstruation.

The basal body temperature significantly increases (choice E) shortly after ovulation, due to the metabolic
effects of progesterone produced by the corpus luteum.