All questions
Question 1
A 45-year-old woman presents to her primary care physician for evaluation of high blood pressure, which was noted at a recent health screening. She has also been experiencing persistent muscle weakness and occasional episodes of tingling in her extremities. Her blood pressure is 165/100 mm Hg. Laboratory studies reveal a serum sodium of 147 mEq/L, potassium of 2.9 mEq/L, and bicarbonate of 31 mEq/L. Plasma renin activity is suppressed.
This patient's constellation of findings is most likely caused by autonomous overproduction of which of the following hormones?
- Aldosterone (correct answer)
- Cortisol
- Norepinephrine
- Dehydroepiandrosterone (DHEA)
Explanation: The patient's presentation of hypertension, hypokalemia, and metabolic alkalosis with suppressed renin activity is classic for primary hyperaldosteronism (Conn's syndrome). Autonomous production of aldosterone from an adrenal adenoma or bilateral adrenal hyperplasia leads to increased sodium and water reabsorption (hypertension) and increased potassium and hydrogen ion excretion (hypokalemia and metabolic alkalosis).
Question 2
A 30-year-old man presents to the emergency department with nausea, vomiting, and profound weakness. He has a history of fatigue, weight loss, and salt craving over the past year. Physical examination shows a blood pressure of 80/50 mm Hg, diffuse hyperpigmentation of the skin and buccal mucosa, and signs of dehydration. Laboratory studies show hyponatremia, hyperkalemia, and hypoglycemia.
The pathophysiology of this patient's acute presentation is best explained by which of the following?
- Isolated glucocorticoid deficiency
- Isolated mineralocorticoid deficiency
- Combined glucocorticoid and mineralocorticoid deficiency (correct answer)
- Excessive catecholamine release
Explanation: This patient is in an adrenal crisis due to primary adrenal insufficiency (Addison's disease), most commonly caused by autoimmune destruction of the adrenal cortex. This leads to a deficiency of both glucocorticoids (cortisol) and mineralocorticoids (aldosterone). Aldosterone deficiency causes hyponatremia, hyperkalemia, and hypotension. Cortisol deficiency contributes to hypotension and causes hypoglycemia. The hyperpigmentation is due to increased MSH production as a byproduct of increased ACTH precursor (POMC) synthesis.
Question 3
A 6-day-old female infant is brought to the emergency department for evaluation of poor feeding, vomiting, and lethargy. Physical examination reveals ambiguous genitalia, dehydration, and hypotension. Laboratory results are significant for a sodium of 125 mEq/L, potassium of 6.8 mEq/L, and metabolic acidosis. A markedly elevated level of 17-hydroxyprogesterone is noted.
This infant's condition is caused by a deficiency of which of the following enzymes?
- 11β-hydroxylase
- 17α-hydroxylase
- 21-hydroxylase (correct answer)
- 5α-reductase
Explanation: The presentation of ambiguous genitalia in a female infant, combined with salt wasting (hyponatremia, hyperkalemia, hypotension) and elevated 17-hydroxyprogesterone, is classic for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. This enzyme defect impairs the synthesis of both cortisol and aldosterone, leading to shunting of precursors towards androgen production, which causes virilization of female fetuses.
Question 4
A 62-year-old woman presents with a 6-month history of fatigue, constipation, and depressed mood. She also reports dull, aching bone pain. Medical history is significant for two episodes of calcium oxalate kidney stones in the past year. Laboratory studies show a serum calcium of 11.5 mg/dL (normal 8.5-10.2), serum phosphate of 2.1 mg/dL (normal 2.5-4.5), and an intact parathyroid hormone (PTH) level of 150 pg/mL (normal 10-65).
Which of the following is the most likely underlying cause of this patient's condition?
- Parathyroid adenoma (correct answer)
- Malignancy-associated hypercalcemia
- Vitamin D intoxication
- Granulomatous disease
Explanation: The patient's symptoms of 'stones, bones, groans, and psychiatric overtones' combined with laboratory findings of hypercalcemia, hypophosphatemia, and an inappropriately elevated PTH level are characteristic of primary hyperparathyroidism. The most common cause (85% of cases) is a benign parathyroid adenoma that autonomously secretes PTH.
Question 5
A 55-year-old woman is evaluated on the second postoperative day following a total thyroidectomy for a large goiter. She complains of tingling around her mouth and muscle cramps in her hands and feet. On physical examination, tapping her cheek just anterior to the ear elicits a twitching of the ipsilateral facial muscles.
This patient's new symptoms are most likely caused by a deficiency of which hormone?
- Thyroxine
- Calcitonin
- Parathyroid hormone (correct answer)
- Aldosterone
Explanation: The patient is exhibiting signs of hypocalcemia (perioral tingling, muscle cramps, and a positive Chvostek sign). The most common cause in this clinical context is iatrogenic hypoparathyroidism resulting from inadvertent removal of or damage to the parathyroid glands during thyroid surgery. The resulting deficiency of parathyroid hormone (PTH) leads to decreased serum calcium and increased serum phosphate.
Question 6
A 10-year-old boy is evaluated for short stature. Physical examination reveals a round face, short neck, and shortened fourth and fifth metacarpals. Laboratory evaluation shows a serum calcium of 7.8 mg/dL, a serum phosphate of 6.0 mg/dL, and a markedly elevated parathyroid hormone (PTH) level. Infusion of exogenous PTH fails to increase urinary cAMP or phosphate excretion.
The pathophysiology of this condition involves a defect in which of the following?
- Calcium-sensing receptor on parathyroid cells
- PTH receptor signal transduction (correct answer)
- Conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D
- Synthesis and secretion of PTH
Explanation: This patient has pseudohypoparathyroidism (specifically, Albright hereditary osteodystrophy), an inherited disorder characterized by end-organ resistance to PTH. The classic findings are hypocalcemia and hyperphosphatemia despite a high PTH level. The failure to respond to exogenous PTH (no increase in urinary cAMP) confirms end-organ resistance. This is most commonly caused by a defect in the Gs alpha subunit, which is crucial for the signal transduction pathway of the PTH receptor.
Question 7
A 55-year-old man with a 20-year history of poorly controlled type 2 diabetes develops progressive renal failure. His urinalysis shows significant proteinuria. A renal biopsy is performed, and light microscopy reveals diffuse thickening of the glomerular basement membrane and expansion of the mesangium.
This characteristic structural change in the glomeruli is primarily a result of which of the following hyperglycemia-induced mechanisms?
- Deposition of amyloid protein
- Non-enzymatic glycosylation of matrix proteins (correct answer)
- Infiltration of the mesangium by inflammatory cells
- Osmotic damage from intracellular sorbitol accumulation
Explanation: Diabetic nephropathy is characterized by pathologic changes in the glomerulus, including thickening of the glomerular basement membrane (GBM) and mesangial expansion. A key mechanism is the non-enzymatic glycosylation of proteins in the GBM and mesangial matrix. This process leads to the formation of advanced glycation end products (AGEs), which cross-link proteins, trapping other proteins like LDL and IgG, and contribute to the thickening and altered function of the GBM, ultimately leading to proteinuria and glomerulosclerosis.
Question 8
A 52-year-old woman presents with a 6-month history of a painful, blistering rash primarily on her lower abdomen, perineum, and legs. She has also experienced a 15-lb weight loss and has been diagnosed with new-onset diabetes. Physical examination shows erythematous plaques with central clearing, blistering, and crusting. Laboratory studies show mild normocytic, normochromic anemia and a fasting glucose of 180 mg/dL.
This patient's syndrome is most likely caused by a tumor secreting which of the following hormones?
- Glucagon (correct answer)
- Insulin
- Somatostatin
- Vasoactive intestinal peptide (VIP)
Explanation: This patient's presentation is classic for glucagonoma syndrome, which is caused by a tumor of the pancreatic alpha cells. The characteristic features include necrolytic migratory erythema (the described rash), diabetes mellitus (due to the catabolic and hyperglycemic effects of glucagon), weight loss, and anemia. The diagnosis is confirmed by a markedly elevated serum glucagon level.
Question 9
A 30-year-old nurse with no significant medical history is found unconscious. Her roommate reports that she has been acting erratically for several weeks. In the emergency department, her blood glucose is 35 mg/dL. She recovers after intravenous dextrose administration. Subsequent laboratory testing during another hypoglycemic episode shows a markedly elevated serum insulin level and a suppressed (very low) C-peptide level.
What is the most likely cause of this patient's condition?
- Factitious disorder due to exogenous insulin use (correct answer)
- Insulin-secreting pancreatic tumor
- Addison's disease
- Hereditary fructose intolerance
Explanation: Factitious hypoglycemia from surreptitious injection of exogenous insulin should be suspected in a healthcare worker with unexplained hypoglycemia. The definitive laboratory finding is a high serum insulin level concurrent with a low C-peptide level. This is because commercial insulin preparations do not contain C-peptide, which is co-secreted with endogenous insulin. An insulinoma would cause elevations in both insulin and C-peptide.
Question 10
A 32-year-old man presents with a 1-year history of decreased libido, erectile dysfunction, and mild headaches. On further questioning, he reports some difficulty with his peripheral vision. Physical examination is notable for gynecomastia and galactorrhea. An MRI of the brain reveals a 1.5 cm sellar mass.
This patient's clinical presentation is most likely caused by a pituitary adenoma oversecreting which hormone?
- Growth hormone (GH)
- Prolactin (correct answer)
- Adrenocorticotropic hormone (ACTH)
- Thyroid-stimulating hormone (TSH)
Explanation: The combination of hypogonadism (decreased libido, erectile dysfunction), galactorrhea, and a pituitary mass is classic for a prolactinoma. Excess prolactin suppresses the hypothalamic-pituitary-gonadal axis by inhibiting GnRH release, leading to low LH, FSH, and testosterone, which causes the hypogonadal symptoms. The headaches and visual field defects (bitemporal hemianopsia) are due to the mass effect of the adenoma on the optic chiasm.
Question 11
A 30-year-old woman presents with anxiety, palpitations, heat intolerance, and a 10-lb weight loss despite a good appetite. Physical examination reveals a heart rate of 110/min, a fine tremor, warm and moist skin, and bilateral exophthalmos. A diffusely enlarged, non-tender thyroid gland is palpated. Laboratory studies show a high free T4 level and a suppressed TSH level.
The underlying pathophysiology of this patient's condition involves which of the following?
- Autoimmune destruction of thyroid follicular cells
- Binding of IgG antibodies to the TSH receptor (correct answer)
- Granulomatous inflammation of the thyroid gland
- A constitutively active mutation of the G-protein coupled TSH receptor
Explanation: This patient's clinical presentation is classic for Graves' disease, the most common cause of hyperthyroidism. The pathophysiology involves the production of autoantibodies (thyroid-stimulating immunoglobulins, TSI) of the IgG class that bind to and activate the TSH receptor on thyroid follicular cells. This mimics the action of TSH, leading to unregulated production and release of thyroid hormones (T3 and T4) and thyroid gland hyperplasia.
Question 12
A 45-year-old woman complains of a 6-month history of fatigue, 15-lb weight gain, and constipation. She constantly feels cold, even in warm weather. Physical examination reveals dry, coarse skin, periorbital edema, and delayed relaxation of deep tendon reflexes. Her thyroid gland is diffusely enlarged, firm, and non-tender. Laboratory studies show an elevated TSH and a low free T4. High titers of anti-thyroid peroxidase antibodies are detected.
A biopsy of this patient's thyroid gland would most likely reveal which of the following histologic findings?
- Extensive fibrosis extending into adjacent neck structures
- Follicular hyperplasia with scant colloid
- Mononuclear infiltrate with germinal center formation (correct answer)
- Multinucleated giant cells and neutrophils
Explanation: The patient has Hashimoto's thyroiditis, the most common cause of hypothyroidism in iodine-sufficient areas. It is an autoimmune disorder characterized by the production of autoantibodies (e.g., anti-thyroid peroxidase, anti-thyroglobulin) and an autoreactive T-cell response against thyroid antigens. The characteristic histologic finding is a massive mononuclear infiltrate of lymphocytes and plasma cells, often with the formation of well-developed germinal centers, along with destruction of thyroid follicles.
Question 13
A 48-year-old man notes that his rings and shoes have become too tight over the past few years. His wife mentions that his facial features have become coarser and he snores loudly. He has also been diagnosed with hypertension and type 2 diabetes mellitus. Physical examination reveals large hands and feet, frontal bossing, and a prognathism. His serum insulin-like growth factor 1 (IGF-1) level is markedly elevated.
The hormone responsible for this patient's condition exerts which of the following metabolic effects?
- Decreases hepatic gluconeogenesis
- Increases insulin sensitivity in peripheral tissues
- Antagonizes the effects of insulin on glucose uptake (correct answer)
- Promotes the conversion of fatty acids to triglycerides in adipose tissue
Explanation: This patient has acromegaly, caused by a growth hormone (GH)-secreting pituitary adenoma. While GH promotes linear growth (via IGF-1), it also has significant metabolic effects. GH is a counterregulatory hormone that antagonizes insulin's effects. It decreases peripheral glucose uptake and increases hepatic gluconeogenesis, leading to hyperglycemia and insulin resistance. This explains the high incidence of diabetes mellitus in patients with acromegaly.
Question 14
A 25-year-old man is hospitalized after a severe motor vehicle accident that resulted in a basilar skull fracture. Five days into his hospital course, his urine output increases dramatically to over 300 mL per hour. Laboratory studies show a serum sodium of 155 mEq/L and a urine specific gravity of 1.002. A water deprivation test shows continued production of dilute urine. However, administration of desmopressin results in a rapid increase in urine osmolality to 600 mOsm/kg.
This patient's polyuria is due to a deficiency in the secretion of a hormone from which of the following locations?
- Adrenal zona glomerulosa
- Anterior pituitary
- Juxtaglomerular apparatus
- Posterior pituitary (correct answer)
Explanation: The patient has developed central diabetes insipidus (DI) as a complication of head trauma. This condition is characterized by a deficiency of antidiuretic hormone (ADH), which is synthesized in the hypothalamus and released from the posterior pituitary. The lack of ADH prevents the insertion of aquaporin-2 channels in the renal collecting ducts, leading to an inability to concentrate urine and resulting in polyuria, hypernatremia, and low urine osmolality. The positive response to desmopressin (an ADH analog) confirms the diagnosis of central (as opposed to nephrogenic) DI.
Question 15
An 82-year-old woman who is largely confined to her home presents with diffuse bone pain and muscle weakness. An X-ray of her femur reveals cortical thinning and a pseudofracture. Laboratory studies are performed with the following results: Serum calcium: 8.0 mg/dL (low), Serum phosphate: 2.2 mg/dL (low), Serum parathyroid hormone: 95 pg/mL (high), Serum alkaline phosphatase: 350 U/L (high).
A deficiency of which of the following is the most likely cause of these findings?
- Calcitonin
- 1,25-dihydroxyvitamin D
- 25-hydroxyvitamin D (correct answer)
- Fibroblast growth factor 23
Explanation: The clinical picture of bone pain, pseudofractures, and labs showing hypocalcemia, hypophosphatemia, and secondary hyperparathyroidism is characteristic of osteomalacia due to vitamin D deficiency. In a housebound elderly individual, this is most often due to inadequate sun exposure and dietary intake, leading to low levels of 25-hydroxyvitamin D, the primary storage form of vitamin D. The low calcium stimulates PTH release, which increases calcium resorption from bone and phosphate excretion by the kidneys.
Question 16
A 40-year-old woman presents with a 2-week history of severe anterior neck pain, fever, and malaise that began shortly after an upper respiratory tract infection. She also reports palpitations and anxiety. On examination, she is febrile to 38.5°C (101.3°F), and her thyroid gland is exquisitely tender to palpation. Laboratory studies show a low TSH, high free T4, and a markedly elevated erythrocyte sedimentation rate (ESR). A radioactive iodine uptake scan shows near-absent uptake.
The initial hyperthyroid phase of this patient's condition is best explained by which of the following mechanisms?
- Formation of thyroid-stimulating immunoglobulins
- Autonomous production of T4 from a thyroid adenoma
- Inflammatory destruction of follicles with release of preformed hormone (correct answer)
- Increased peripheral conversion of T4 to T3
Explanation: This patient's presentation of a painful, tender thyroid, fever, and transient hyperthyroidism following a viral illness is classic for subacute granulomatous (de Quervain's) thyroiditis. The underlying pathophysiology involves a viral or post-viral inflammatory process that damages thyroid follicles. This damage leads to the unregulated release of large quantities of preformed T4 and T3 into the circulation, causing the initial hyperthyroid phase. The inflammation also damages the iodine uptake mechanism, leading to the characteristic low radioactive iodine uptake.
Question 17
A 12-year-old boy is brought to the emergency department with a 1-week history of increased urination, excessive thirst, and a 10-lb weight loss. On examination, he is lethargic, has dry mucous membranes, and is breathing deeply and rapidly. His breath has a fruity odor. A fingerstick glucose is 450 mg/dL. Urinalysis is positive for glucose and ketones.
The primary pathogenic mechanism responsible for this patient's condition is which of the following?
- Peripheral tissue insensitivity to insulin
- Autoimmune-mediated destruction of pancreatic β-cells (correct answer)
- Excessive glucagon secretion from an α-cell tumor
- A gain-of-function mutation in the insulin receptor
Explanation: The patient's presentation with polyuria, polydipsia, weight loss, and diabetic ketoacidosis (DKA) is classic for new-onset type 1 diabetes mellitus. The underlying pathophysiology of type 1 DM is a T-cell mediated autoimmune destruction of the insulin-producing β-cells in the pancreatic islets. The resulting absolute insulin deficiency leads to hyperglycemia and unchecked lipolysis and ketogenesis, causing DKA.
Question 18
A 38-year-old woman is evaluated for progressive central obesity, facial plethora, and easy bruising. Her blood pressure is 150/95 mm Hg. A 24-hour urine free cortisol level is significantly elevated. A low-dose dexamethasone suppression test fails to suppress cortisol levels. However, a high-dose dexamethasone suppression test results in a 70% decrease in urinary cortisol excretion. Plasma ACTH level is elevated.
These findings are most consistent with a hormone-secreting tumor located in which of the following organs?
- Adrenal cortex
- Anterior pituitary (correct answer)
- Lung
- Pancreas
Explanation: This patient has Cushing's disease, which is caused by an ACTH-secreting pituitary adenoma. The elevated ACTH stimulates the adrenal glands to produce excess cortisol. The key diagnostic finding is the suppression of cortisol production with high-dose dexamethasone, which indicates that the tumor is still partially responsive to negative feedback, a characteristic feature of pituitary adenomas but not of ectopic ACTH-producing tumors (e.g., from the lung) or adrenal adenomas.
Question 19
A 45-year-old woman presents with recurrent episodes of confusion, palpitations, and diaphoresis. These episodes typically occur in the morning before breakfast and are relieved by consuming juice or a meal. During a supervised fast in the hospital, she develops symptomatic hypoglycemia with a blood glucose of 40 mg/dL. Simultaneous laboratory tests reveal a high serum insulin level and a high serum C-peptide level.
Which of the following is the most likely cause of this patient's hypoglycemia?
- Surreptitious administration of exogenous insulin
- Overdose of a sulfonylurea drug
- Pancreatic β-cell tumor (correct answer)
- Reactive hypoglycemia after a meal
Explanation: The patient exhibits Whipple's triad (symptoms of hypoglycemia, low plasma glucose, and relief of symptoms with glucose administration), which is suggestive of true hypoglycemia. The key to the diagnosis is the laboratory finding of high insulin AND high C-peptide levels during a hypoglycemic episode. This indicates endogenous hyperinsulinism, most commonly caused by an insulinoma (a pancreatic β-cell tumor). Exogenous insulin would lead to high insulin but low C-peptide, as C-peptide is cleaved from proinsulin during endogenous insulin synthesis.
Question 20
A 68-year-old man with a history of poorly controlled type 2 diabetes is brought to the emergency department by his family due to progressive confusion over the past few days. He has had a productive cough and fever. Examination reveals severe dehydration. Laboratory results show a plasma glucose of 950 mg/dL, serum sodium of 150 mEq/L, and a calculated serum osmolality of 360 mOsm/kg. Arterial blood gas shows a pH of 7.35 and serum ketones are negative.
The absence of significant ketoacidosis in this patient is best explained by the presence of which of the following?
- Sufficient endogenous insulin to inhibit lipolysis (correct answer)
- Impaired renal excretion of ketones
- Suppression of glucagon by severe hyperglycemia
- Lower levels of counterregulatory hormones compared to DKA
Explanation: This patient has Hyperosmolar Hyperglycemic State (HHS), a complication of type 2 diabetes. Unlike DKA, where there is an absolute insulin deficiency, patients with HHS have a relative insulin deficiency. There is enough circulating endogenous insulin to suppress ketogenesis (by inhibiting hormone-sensitive lipase in adipose tissue) but not enough to promote adequate glucose uptake by peripheral tissues, leading to severe hyperglycemia and hyperosmolarity.