A 32-year-old woman comes to the office due to 6 months of persistent diarrhea. She has had 8-10 episodes a day of tea-colored, odorless, watery stools. The symptoms have persisted despite a lactose-free diet and a fasting trial. The patient has had no abdominal pain, fever, or vomiting. Temperature is 36.7 C (98 F). Abdominal examination is unremarkable. Sampling of her gastric contents shows a total lack of gastric acid secretion. Somatostatin treatment promptly relieves the symptoms. An excess of which of the following hormones is most likely responsible for this patient's symptoms?

Question

A 32-year-old woman comes to the office due to 6 months of persistent diarrhea.  She has had 8-10 episodes a day of tea-colored, odorless, watery stools.  The symptoms have persisted despite a lactose-free diet and a fasting trial.  The patient has had no abdominal pain, fever, or vomiting.  Temperature is 36.7 C (98 F).  Abdominal examination is unremarkable.  Sampling of her gastric contents shows a total lack of gastric acid secretion.  Somatostatin treatment promptly relieves the symptoms.  An excess of which of the following hormones is most likely responsible for this patient's symptoms?

Quizplus · Accepted Answer

This patient has secretory diarrhea, distinguished from inflammatory diarrhea by the absence of blood or pus and from osmotic diarrhea (eg, due to lactose intolerance) by its failure to improve with dietary modification. Excess vasoactive intestinal peptide (VIP) secretion due to a pancreatic islet cell tumor called VIPoma can result in watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome (pancreatic cholera). VIP stimulates pancreatic bicarbonate and chloride secretion, and its binding to intestinal epithelial cells leads to adenylate cyclase activation and increased cyclic AMP production, causing sodium, chloride, and water secretion into the bowel (secretory watery diarrhea, often >3 L/day). Somatostatin (octreotide) decreases the production of many gastrointestinal (GI) hormones (eg, VIP, gastrin, glucagon, cholecystokinin [CCK]). Its inhibition of VIP production by this VIPoma is responsible for the resolution of this patient's symptoms. (Choice A) CCK causes increased secretion of pancreatic enzymes and bicarbonate, gallbladder contraction, and inhibition of gastric emptying. It does not cause WDHA syndrome. CCK is produced by I cells of the proximal small bowel mucosa in response to fatty acids and amino acids. (Choice B) Gastrin is produced by G cells in the stomach mucosa. It stimulates gastric acid production and growth of the gastric mucosa. Gastrinomas classically cause intractable peptic ulcer disease (Zollinger-Ellison syndrome), not WDHA syndrome. (Choice C) Ghrelin is produced in the stomach and regulates food intake. Levels increase in fasting states and fall after eating. Ghrelin antagonists are being investigated as drug targets. (Choice D) A glucagonoma is a pancreatic alpha cell tumor that hypersecretes glucagon and can cause secondary diabetes mellitus and necrolytic migratory erythema of the skin. (Choice E) Motilin is produced by the duodenal mucosa and stimulates smooth muscle contraction in the upper GI tract. The antibiotic erythromycin acts as an agonist at motilin receptors in the stomach and duodenum, contributing to the drug's GI side effects. Educational objective: VIPomas are pancreatic islet cell tumors that hypersecrete vasoactive intestinal peptide (VIP), which increases intestinal chloride loss into the stool and causes excess losses of the accompanying water, sodium, and potassium. VIP also inhibits gastric acid secretion. Somatostatin inhibits the secretion of VIP and is used to treat the symptoms of VIPoma. __________ References: Sporadic pancreatic vasoactive intestinal peptide-producing tumor (VIPoma) in a 47-year-old male. (http://www.ncbi.nlm.nih.gov/pubmed/24785507) The physiological roles of secretin and its receptor. (http://www.ncbi.nlm.nih.gov/pubmed/25332973)

A 32-Year-Old Woman Comes to the Office Due to 6