Pre-Test

Endocrinology

dr. Afdol Rahmadi

 Question #1
A 43-year-old man with a history of goiter undergoes a
thyroidectomy. One week later, he returns to the physician
because of carpopedal spasms, muscle and abdominal
cramps, and tingling of his lips and hands. Laboratory
studies show a serum calcium of 6.2 mg/dL and serum
phosphorous of 5.7 mg/dL. Physical examination shows
tetany of the facial muscles upon tapping the patient's face
in front of the ear.

Which of the following drugs will most likely improve this

patient's symptoms?

a. Bumetanide
b. Ergocalciferol
c. Levothyroxine
d. Metolazone
e. Pamidronate
 Question #1
A 43-year-old man with a history of goiter undergoes a
thyroidectomy. One week later, he returns to the physician
because of carpopedal spasms, muscle and abdominal
cramps, and tingling of his lips and hands. Laboratory
studies show a serum calcium of 6.2 mg/dL and serum
phosphorous of 5.7 mg/dL. Physical examination shows
tetany of the facial muscles upon tapping the patient's face
in front of the ear.

Which of the following drugs will most likely improve this

patient's symptoms?

a. Bumetanide
b. Ergocalciferol
c. Levothyroxine
d. Metolazone
e. Pamidronate
This patient is presenting with signs and symptoms
highly suggestive of hypoparathyroidism, a
condition that occurs most frequently after
thyroidectomy or the removal of a parathyroid
adenoma.
Hypoparathyroidism is a condition of parathyroid
hormone (PTH) deficiency leading to
decreased calcium levels and other
electrolyte abnormalities. Normally a fall in
extracellular fluid ionized calcium concentration
leads to stimulation of PTH secretion.
When released, PTH enhances active reabsorption
of calcium and magnesium from distal tubules and
the thick ascending limb in the kidney, enhances
the release of calcium from bones and enhances
the absorption of calcium in the intestine by
increasing the production of activated vitamin D.
However, in hypoparathyroidism, PTH levels are
Hypoparathyroidism is characterized by severe
hypocalcemia and hyperphosphatemia,
resulting in tetany, carpopedal spasms, muscle
and abdominal cramps, and tingling of the lips
and hands.
A positive Chvostek sign (tapping the face in
front of the ear elicits tetany) and Trousseau
sign (abnormal muscular contractions elicited by
applying a blood pressure cuff) will often be
noted.
Since the blood calcium levels are often very low,
either calcium gluconate or vitamin D
preparations should be administered to correct
the condition.
Vitamin D preparations, such as ergocalciferol
(vitamin D2), elevate calcium levels, and also
increase phosphate levels.
 Bumetanide
a loop diuretic used to treat various edematous states; this
product is contraindicated in patients with hypoparathyroidism
because it decreases blood calcium levels, which will worsen
the condition

 Levothyroxine
used as replacement therapy for diminished or absent thyroid
function. Although patients with hypoparathyroidism may also
be hypothyroid, the use of levothyroxine will not correct the
hypocalcemia and hyperphosphatemia

 Metolazone
thiazide diuretic that would be expected to modestly increase
the patient's calcium level. However, even though this agent
is associated with increasing calcium levels, it is not used to
treat hypocalcemia

 Pamidronate
in a patient with hypoparathyroidism is contraindicated since
this agent is used to treat hypercalcemia and would
subsequently worsen the patient's hypocalcemia.
Question #2
A 62-year-old woman with a history of type 2 diabetes mellitus begins treatment
with a new drug. One week later, she comes to the physician because of malaise,
myalgias, respiratory distress, and daytime somnolence. Laboratory studies show:

PCO2 34 mm Hg
HCO3 15 mmol/L
Arterial blood pH 7.27
Sodium 142 mEq/L
Potassium 5.0 mEq/L
Chloride 102 mEq/L

Urinalysis is negative for ketones. Which of the following drugs is this

patient most likely receiving?

a. Glucagon
b. Glyburide
c. Metformin
d. Miglitol
e. Repaglinide
Question #2
A 62-year-old woman with a history of type 2 diabetes mellitus begins treatment
with a new drug. One week later, she comes to the physician because of malaise,
myalgias, respiratory distress, and daytime somnolence. Laboratory studies show:

PCO2 34 mm Hg
HCO3 15 mmol/L
Arterial blood pH 7.27
Sodium 142 mEq/L
Potassium 5.0 mEq/L
Chloride 102 mEq/L

Urinalysis is negative for ketones. Which of the following drugs is this

patient most likely receiving?

a. Glucagon
b. Glyburide
c. Metformin
d. Miglitol
e. Repaglinide

Lactic acidosis, characterized by
elevated blood lactate, decreased
arterial blood pH, decreased
bicarbonate, and electrolyte
imbalances with an elevated anion
gap (normal = 10–12), is a rare but
serious complication of metformin
administration. In patients with normal
renal function, excess lactic acid is
cleared through the kidneys.
However, in a patient with renal
impairment, both metformin and
lactic acid are cleared less
effectively, which may result in
further accumulation of both.
The complication of lactic
acidosis is serious and a
potentially fatal side effect of
metformin.
Calculation of the anion gap in this patient is as follows:
= [Na+] - ([Cl-] + [HCO3-])
= 142 - (102 + 15)
= 25

The onset of lactic acidosis is usually accompanied
by several nonspecific signs and symptoms,
including malaise, myalgias, respiratory distress,
and increased somnolence.
There may be associated hypothermia,
hypotension, and resistant bradyarrhythmias as
the condition progresses. When this condition
occurs, it is fatal in approximately 50% of cases.
Metformin should not be used in patients with renal
insufficiency, heart failure, conditions predisposing
to hypoxemia, or lactic acidosis. Another class of
drugs associated with lactic acidosis are the
nucleoside reverse transcriptase inhibitors (NRTIs),
such as zidovudine, didanosine, lamivudine, and
emtricitabine.
Glucagon (choice A) is a polypeptide hormone produced
by the alpha cells of the islets of Langerhans in the
pancreas. It stimulates the conversion of glycogen to
glucose in the liver. This hormone is available
commercially to be administered in an intramuscular
injection for the emergency treatment of severe
hypoglycemia in diabetic patients when the
administration of oral glucose is not possible. The most
common adverse effects include pain at the site of the
injection as well as hyperglycemia.
Glyburide (choice B) is a sulfonylurea associated with
the development of hypoglycemia and cholestatic
jaundice (a rare complication).
Miglitol (choice D) is an alpha-glucosidase inhibitor
commonly associated with the development of
abdominal discomfort and flatulence.
Repaglinide (choice E) is the non-sulfonylurea moiety
of glyburide; it is commonly associated with
hypoglycemia, nausea, and vomiting.
 Question #3
A 45-year-old woman comes to the physician because of a severe sore
throat. Her temperature is 38.5ºC (101.3ºF). Six weeks ago, the
patient had an upper respiratory infection that resolved on its own.
Physical examination shows an extremely tender, enlarged thyroid
gland, but no erythema of the throat. Serum studies show a T4 of 16
µg/dL, T3 of 200 ng/dL, TSH of 0.3 µU/mL, and an ESR of 30 mm/hour.
Two months later, the patient is asymptomatic and thyroid function
tests have returned to normal. She never again experiences difficulty
with her thyroid function.

Which of the following is the most likely cause of her transient

hyperthyroidism?

a. Diffuse nontoxic goiter

b. Graves disease
c. Hashimoto thyroiditis
d. Subacute granulomatous thyroiditis
 Question #3
A 45-year-old woman comes to the physician because of a severe sore
throat. Her temperature is 38.5ºC (101.3ºF). Six weeks ago, the
patient had an upper respiratory infection that resolved on its own.
Physical examination shows an extremely tender, enlarged thyroid
gland, but no erythema of the throat. Serum studies show a T4 of 16
µg/dL, T3 of 200 ng/dL, TSH of 0.3 µU/mL, and an ESR of 30 mm/hour.
Two months later, the patient is asymptomatic and thyroid function
tests have returned to normal. She never again experiences difficulty
with her thyroid function.

Which of the following is the most likely cause of her transient

hyperthyroidism?

a. Diffuse nontoxic goiter

b. Graves disease
c. Hashimoto thyroiditis
d. Subacute granulomatous thyroiditis
This patient most likely has subacute
granulomatous (de Quervain) thyroiditis, which
frequently develops a few weeks after a viral
infection. Microscopically, it is characterized by
microabscess formation within the thyroid,
eventually progressing to granulomatous
inflammation with multinucleated giant cells.
Clinically, the most important distinguishing
feature of this type of thyroiditis is pain as a
presenting symptom (almost 96% of
patients). The pain may be located near the
thyroid or radiate to the jaw, throat, or ears. Other
non-specific symptoms include fever, malaise, and
myalgia.
On physical examination, the patient usually
presents with significant tenderness to
palpation of the thyroid gland, along with
evidence of thyroid enlargement. Another
important feature is recovery of thyroid function
after several weeks.
During the acute phase of the illness, many patients present
with transient hyperthyroidism. This is a common feature of
many forms of thyroiditis, and is caused by destruction of the
thyroid follicles and spillage of preformed thyroid hormones
into the circulation.
The disease usually abates within 6 to 8 weeks and is often
followed by a euthyroid or hypothyroid state for 2 to 4 months,
explained by depletion of the preformed hormones and
destruction of follicular cells. ESR is elevated in these patients
(nonspecific), and there is low radioactive iodine uptake due to
follicular cell dysfunction (as with many types of
thyroiditis). Treatment is with anti-inflammatory drugs
including NSAIDs or prednisone.
For painful thyroiditis, important differential diagnoses include
acute infectious thyroiditis and hemorrhage into a thyroid
nodule. Unlike subacute thyroiditis, acute infectious thyroiditis
usually presents with an elevated white count and possibly an
abscess on ultrasound. Additionally, thyroid function is usually
normal in acute infectious thyroiditis.
 Diffuse nontoxic goiter
does not produce hyperthyroidism. Diffuse nontoxic goiter grows insidiously and is usually
not painful. Patients present with compressive symptoms of their airway or esophagus due
to the expanding mass

 Graves Disease
Although characterized by a diffuse goiter, the hyperthyroidism of Graves disease does
not spontaneously remit. Graves disease is an autoimmune disease where IgG antibodies
are produced against thyroid-stimulating hormone (TSH) receptors. Other characteristic
pathology in these patients includes exophthalmos, tachycardia, heat intolerance, and
pre-tibial myxedema.

 Hashimoto thyroiditis
a chronic autoimmune condition that can also cause transient hyperthyroidism but then
progresses to a more chronic hypothyroidism (unlike our patient's resolving thyroid
function). It is a painless condition. Several circulating antibodies described in this
condition include anti-TPO (thyroid peroxidase), anti-TG (thyroglobulin), and anti-
microsomal antibodies. Histology shows a lymphocytic infiltrate with germinal centers in
the gland, along with the presence of Hurthle cells. These patients are at risk for
development of non-Hodgkin B cell lymphoma of the thyroid.

 Subacute lymphocytic thyroiditis

an cause transient hyperthyroidism but is characteristically painless. The disease is a
variant of Hashimoto thyroiditis, which presents with full recovery of thyroid function
(unlike Hashimoto's). A version of this disease occurs in women within a year of delivery
or abortion called post-partum thyroiditis.
Question #4
A 38-year-old woman comes to the physician because of
excessive thirst and urination for the past 4 weeks. Her
appetite has been normal, but she has lost 6.8 kg (15 lb) in 1
month. Physical examination shows erythematous
necrotizing skin eruptions on her legs. Her fasting blood
glucose is 170 mg/dL. A CT scan shows a tumor in the tail of
the pancreas.

Which of the following is the most likely cell from which the
pancreatic tumor is derived?

a. Acinar cell
b. Alpha cell
c. Beta cell
d. Delta cell
Question #4
A 38-year-old woman comes to the physician because of
excessive thirst and urination for the past 4 weeks. Her
appetite has been normal, but she has lost 6.8 kg (15 lb) in 1
month. Physical examination shows erythematous
necrotizing skin eruptions on her legs. Her fasting blood
glucose is 170 mg/dL. A CT scan shows a tumor in the tail of
the pancreas.

Which of the following is the most likely cell from which the
pancreatic tumor is derived?

a. Acinar cell
b. Alpha cell
c. Beta cell
d. Delta cell
 The symptoms described are typical for a patient with glucagon excess secondary to a
glucagonoma. Increased glucagon causes a syndrome similar to diabetes mellitus with
increased thirst/appetite, weight loss, and excessive urination (glucose acts as an osmotic
agent in the kidney). Glucagon increases glycogenolysis and gluconeogenesis in the liver,
resulting in elevated systemic glucose levels. However, in these patients, insulin-producing
beta cells are still functional, thus extremely elevated glucose levels and diabetic
ketoacidosis are rare.

Glucagon is secreted by alpha cells of the pancreatic islets of Langerhans. Increased levels
are rare and are usually due to carcinoma (70%) or adenoma (30%) of the islets. Patients
also have migratory skin rashes (necrolytic migratory erythema), alopecia,
hyperpigmentation of the skin and glossitis. Diagnosis is made by measuring glucagon
levels. Treatment includes surgical resection and octeotride (somatostatin) to reduce
glucagon output.
 The acinar cell (choice A), the main exocrine cell of the pancreas, contains digestive enzymes.
Auto-digestion of the pancreas by premature activation of these enzymes (especially amylase and
lipase) occurs in pancreatitis. Acute pancreatitis is an emergent medical condition characterized by
abdominal pain radiating to the back (retroperitoneal organ) and elevation in serum amylase/lipase.
Chronic pancreatitis produces chronic abdominal pain and is associated with fibrosis and atrophy of
the acinar structures, and pseudocyst formation.

Beta cells (choice C) are responsible for insulin release. An adenoma of beta cells (insulinoma)
would cause hyperinsulinism. Insulin ultimately decreases serum glucose through inhibition of
glucagon and increased uptake of glucose by muscle and adipose tissue (via GLUT-4 receptor), thus
decreasing glucose availability for other organs. Symptoms of hypoglycemia include dizziness,
confusion, sweating, anxiety, and tachycardia. These symptoms result from a combination of
adrenergic activation (epinephrine can mobilize glucose stores) and decreased glucose availability
for the brain. Glucose needs to be given promptly to avoid coma and death. The characteristic lab
findings with insulinoma is elevated insulin and C-peptide plus decreased blood glucose. The C-
peptide helps distinguish an insulinoma from exogenous/surreptitious insulin use (C-peptide is only
produced in pancreas and not in injected synthetic insulin).
 Delta cells (choice D) are islet cells that secrete somatostatin. Somatostatinomas are
usually malignant. Clinically, a diabetes mellitus-like syndrome occurs (via somatostatin
inhibition of insulin) along with diarrhea/steatorrhea (via somatostatin inhibition of pancreatic
lipase/bicarbonate release) and cholelithiasis (via somatostatin inhibition of CCK and
gallbladder contractility). Diagnosis is made from elevated serum somatostatin levels, but
can be difficult because of the hormone's short half-life.

The G cell (choice E) is the islet cell that secretes gastrin. Gastrin excess is usually
associated with gastrinomas, 70% of which are malignant. Zollinger-Ellison syndrome causes
low gastric and duodenal pH, multiple gastric/duodenal ulcers, and diarrhea/steatorrhea (low
pH inactivates pancreatic enzymes). Diagnosis is made from high serum gastrin levels.
 Many of these pancreatic islet cell tumors can be found as part of multiple
endocrine neoplasia type I (MEN I), a neuroendocrine syndrome characterized by
a triad of pituitary adenoma + hyperparathyroidism + pancreatic islet cell
tumors.

Many of these pancreatic islet cell tumors can be found as part of multiple
endocrine neoplasia type I (MEN I), a neuroendocrine syndrome characterized by
a triad of pituitary adenoma + hyperparathyroidism + pancreatic islet cell
tumors.
 Question #5
A 42-year-old man comes to the physician because of a neck mass, hoarseness, and
diarrhea. He has a history of a previously resected pheochromocytoma. Physical
examination shows 4 palpable soft nodules present in both thyroid lobes. He undergoes
thyroid gland resection. Gross examination of the thyroid gland shows multifocal tumor
with hemorrhage, necrosis, and spread outside the thyroid capsule. On histologic
examination, the tumor is composed of uniform polygonal cells arranged in nests. There
is also an abundance of parafollicular protein, which demonstrate apple-green
birefringence under polarized light when stained with Congo Red.

Which of the following was most likely being secreted by the tumor cells in this patient?

a. Calcitonin
b. Parathyroid hormone
c. Thyroid-stimulating hormone (TSH)
d. Thyroxine (T4)
e. Triiodothyronine (T3)
 Question #5
A 42-year-old man comes to the physician because of a neck mass, hoarseness, and
diarrhea. He has a history of a previously resected pheochromocytoma. Physical
examination shows 4 palpable soft nodules present in both thyroid lobes. He undergoes
thyroid gland resection. Gross examination of the thyroid gland shows multifocal tumor
with hemorrhage, necrosis, and spread outside the thyroid capsule. On histologic
examination, the tumor is composed of uniform polygonal cells arranged in nests. There
is also an abundance of parafollicular protein, which demonstrate apple-green
birefringence under polarized light when stained with Congo Red.

Which of the following was most likely being secreted by the tumor cells in this patient?

a. Calcitonin
b. Parathyroid hormone
c. Thyroid-stimulating hormone (TSH)
d. Thyroxine (T4)
e. Triiodothyronine (T3)
 This patient presents with medullary carcinoma of the thyroid, which can occur sporadically or as part of
multiple endocrine neoplasia (MEN) types 2A and 2B. Medullary thyroid cancer derives from thyroid
parafollicular cells (C-cells), which produce calcitonin (choice A), an important antagonist to PTH. C-cells
have a neuroendocrine origin and are derived from the neural crest.

There are two major clues in this patient's history point towards medullary thyroid cancer. First, the
pathologic findings reveal the local production of amyloid, which present as protein that demonstrates apple-
green birefringence when viewed under polarized light with Congo Red stain. When comparing thyroid
cancers, the presence of amyloid is unique to medullary thyroid cancer. The amyloid derives from
precipitated calcitonin.

Second, the patient's diarrhea is a major clinical symptom of medullary thyroid cancer. Diarrhea and
occasional flushing results from elevated calcitonin levels. The patient's history of pheochromocytoma should
make you think of MEN type 2 in this patient.
 The chart demonstrates the characteristics of different
MEN syndrome. All three are autosomal dominant.

Parathyroid hormone (choice B) can be produced by parathyroid tumors (adenoma or carcinoma). Similarly,
parathyroid hormone-related protein (PTHrP) is produced as part of a paraneoplastic syndrome by many non-
parathyroid cancers. These include squamous cell lung cancer, breast cancer, and renal cell carcinoma. In the case of
both parathyroid hormone and PTHrP, the result is hyperparathyroidism, which produces calcium kidney stones
(stones), hypercalcemia (bones), constipation/ulcers (groans), and depression (psychiatric overtones).

TSH (choice C) can be produced by pituitary adenomas, although rarely. Pituitary adenomas far more often produce
prolactin or growth hormone. Patient symptoms are consistent with that of hyperthyroidism including weight loss,
sweating, tachycardia, and irritability.

T3, or triiodothyronine (choice E), and T4, or thyroxine (choice D), can also be produced in excess and
generate symptoms of hyperthyroidism. Causes include thyroid adenoma, thyroid hyperplasia, and thyroid cancer.
THANK YOU