Each week, Osmosis shares a USMLE® Step 1-style practice question to test your knowledge of medical topics. Today’s case involves a 34-year-old woman with tea-colored diarrhea for the last 2 months. She experiences muscle cramps and feels weak. Can you figure it out?
A 34-year-old woman comes to the office complaining of consistent diarrhea for the last 2 months. The patient has experienced watery, tea-colored diarrhea that happens even when she has not eaten anything. She denies any associated abdominal pain or difficulty swallowing. The patient feels fatigued and weak with muscle cramps which she attributes to being dehydrated. Medical history includes hyperparathyroidism and nephrolithiasis. The patient’s temperature is 37.0°C (98.6°F), pulse is 100/min, respirations are 20/min, and blood pressure is 100/60 mmHg. Physical examination shows dry mucous membranes and decreased skin turgor without abdominal tenderness. Laboratory tests show the following:
| Laboratory value | Result |
| Sodium | 144 mEq/L |
| Potassium | 2.5 mEq/L |
| Chloride | 93 mEq/L |
| Bicarbonate | 21 mEq/L |
| Calcium | 12 mg/dL |
| Glucose | 250 mg/dL |
| Parathyroid hormone | 350 pg/mL |
Which of the following is the most likely mechanism of this patient’s symptoms?
A. Calcitonin secretion
B. Catecholamine secretion
C. Gastrin secretion
D. Somatostatin secretion
E. Vasoactive intestinal peptide secretionScroll down to find the answer!
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The correct answer to today’s USMLE® Step 1 Question is…
E. Vasoactive intestinal peptide secretion
Before we get to the Main Explanation, let’s look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!
Incorrect answer explanations
The incorrect answers to today’s USMLE® Step 1 Question are…
A. Calcitonin secretion
Incorrect: Calcitonin is a peptide hormone released by the parafollicular cells (C cells) of the thyroid gland. Its normal function is to reduce serum calcium levels, opposing the actions of parathyroid hormone (PTH). Calcitonin levels can be elevated from medullary thyroid cancer, which is seen in MEN type 2A and MEN type 2B, but it is unlikely to be seen in this patient with MEN type 1.
B. Catecholamine secretion
Incorrect: Tumor secretion of the catecholamines norepinephrine, epinephrine, and dopamine are responsible for the symptoms associated with a pheochromocytoma, including hypertension, headache, sweating, and tachycardia. Pheochromocytoma is almost never associated with MEN type 1, from which this patient likely suffers.
C. Gastrin secretion
Incorrect: Gastrin is a peptide hormone released by the G cells in the pyloric antrum of the stomach, duodenum, and pancreas that stimulates secretion of gastric acid by the parietal cells of the stomach. Gastrinomas, specifically of pancreatic origin, are associated with MEN type 1; however, they typically cause upper gastrointestinal ulcers and gastroesophageal reflux disease (GERD), as opposed to this patient’s persistent diarrhea and electrolyte derangements.
D. Somatostatin secretion
Incorrect: Somatostatin is a peptide hormone secreted by delta cells in the pyloric antrum of the stomach, duodenum, and pancreas that acts on G protein-coupled somatostatin receptors to inhibit the release of several secondary hormones, including insulin and glucagon. Somatostatin analogues are used in the treatment of several neuroendocrine tumors.
Main Explanation:
This patient’s gastrointestinal symptoms are caused by the effects of excess vasoactive intestinal peptide (VIP) from a VIPoma. VIP is a neuropeptide that functions as a neuromodulator and neurotransmitter, and a VIPoma is a rare endocrine tumor that usually originates from the non-β islet cells of the pancreas. VIP’s effects include vasodilation, smooth muscle relaxation, and bicarbonate secretion from bile duct cholangiocytes. In excess, VIP binds to intestinal epithelial cells, increasing cAMP and causing fluid and electrolyte secretion into the lumen, which results in profuse secretory diarrhea with hypokalemia and metabolic acidosis. Electrolyte derangements and dehydration cause symptoms of fatigue, muscle cramps, flushing, and weakness.
VIPomas are associated with multiple endocrine neoplasia syndrome type 1 (MEN type 1). MEN1 is a gene that is found on chromosome 11 and codes for a tumor suppressor protein called menin, which normally stops cells from dividing uncontrollably. MEN1 mutations cause MEN type 1, which is an autosomal dominant genetic disorder. There are three types of tumors associated with MEN type 1: parathyroid, pancreatic, and pituitary. This patient has a history of hyperparathyroidism from a parathyroid adenoma, as well as symptoms consistent with a pancreatic tumor, the VIPoma, suggesting a diagnosis of MEN type 1.
Other pancreatic tumors that can occur in MEN type 1 include gastrinomas (stomach ulcers) and insulinomas (hypoglycemia) or glucagonomas (hyperglycemia). Pituitary adenomas may include prolactinomas (galactorrhea, gynecomastia) and growth hormone-releasing tumors (gigantism, acromegaly). Although parathyroid tumors can also occur in MEN type 2, pancreatic and pituitary tumors are exclusively found in MEN type 1.
Major Takeaway:
The autosomal dominant, multiple endocrine neoplasia syndrome type 1 (MEN type 1) is caused by a deactivating mutation in the MEN1 tumor suppressor gene on chromosome 11 and is characterized by tumors in the “Three P’s”: parathyroid, pituitary, and pancreas. The pancreatic tumor “VIPoma” causes profuse secretory diarrhea with resultant hypokalemia, muscle weakness and fatigue, often in the absence of abdominal pain.
References:
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The United States Medical Licensing Examination (USMLE®) is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). Osmosis is not affiliated with NBME nor FSMB.
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