A 43-year-old man presents to his physician with recurrent epigastric pain and chronic diarrhea. During the past 2 years, he has undergone treatment for multiple peptic ulcers that have developed despite adherence to high-dose proton pump inhibitor therapy. His medical history is significant for recurrent nephrolithiasis and primary hyperparathyroidism. Temperature is 36.8°C (98.2°F), blood pressure is 122/76 mm Hg, pulse is 78/min, and respiratory rate is 14/min. Upper endoscopy reveals multiple ulcers involving the distal duodenum.
Which of the following is the most likely underlying diagnosis?
The correct answer is:
B) Gastrinoma
This patient has Zollinger-Ellison syndrome caused by a gastrin-secreting neuroendocrine tumor (gastrinoma). Several clues point toward this diagnosis. First, he has recurrent peptic ulcers despite appropriate medical therapy. Second, the ulcers extend into the distal duodenum, a classic finding because extreme acid production can overwhelm normal protective mechanisms throughout the proximal small intestine. Third, chronic diarrhea is common in Zollinger-Ellison syndrome because excessive gastric acid inactivates pancreatic enzymes and damages intestinal mucosa. Finally, his history of primary hyperparathyroidism strongly suggests Multiple Endocrine Neoplasia Type 1 (MEN1), which is commonly associated with gastrinomas.
Gastrinomas cause marked hypergastrinemia and gastric acid hypersecretion. Patients often present with refractory peptic ulcer disease, multiple ulcers, recurrent ulcers, diarrhea, or gastroesophageal reflux symptoms. Diagnosis involves measurement of fasting gastrin levels and confirmatory testing when needed. Treatment includes high-dose proton pump inhibitors and localization of the tumor for potential surgical management. Approximately 20%–30% of gastrinomas occur in association with MEN1 syndrome.
Answer choice A: Achalasia, is incorrect.
Achalasia causes progressive dysphagia to solids and liquids due to impaired lower esophageal sphincter relaxation. It does not cause recurrent peptic ulcer disease, distal duodenal ulcers, or diarrhea.
Answer choice C: H. pylori gastritis, is incorrect.
H. pylori infection is the most common cause of peptic ulcer disease and is therefore a tempting answer choice. However, H. pylori typically causes isolated gastric or proximal duodenal ulcers and would not explain multiple refractory ulcers, distal duodenal involvement, chronic diarrhea, and MEN1-associated findings.
Answer choice D: Primary biliary cholangitis, is incorrect.
PBC is an autoimmune cholestatic liver disease characterized by pruritus, fatigue, and positive antimitochondrial antibodies. It has no relationship to gastric acid hypersecretion.
Answer choice E: Ulcerative colitis, is incorrect.
Ulcerative colitis causes chronic inflammatory diarrhea and hematochezia but does not produce recurrent peptic ulcer disease or hypergastrinemia.
Key Learning Point
Recurrent or refractory peptic ulcers, especially when accompanied by diarrhea or ulcers distal to the duodenal bulb, should raise suspicion for Zollinger-Ellison syndrome caused by a gastrinoma.
