A 55-year-old man comes to the office due to intermittent abdominal pain. He has no difficulty or pain with swallowing. The patient occasionally uses over-the-counter pain medicine for osteoarthritis of the right knee. He does not use alcohol or tobacco and has no history of cancer in the family. He works as an air traffic controller at a busy airport. Upper gastrointestinal endoscopy shows an ulcer in the distal duodenum. Fasting serum gastrin concentration is at the upper limit of normal and rises in response to intravenous secretin. This patient's condition is most likely caused by which of the following processes?

Question

A 55-year-old man comes to the office due to intermittent abdominal pain.  He has no difficulty or pain with swallowing.  The patient occasionally uses over-the-counter pain medicine for osteoarthritis of the right knee.  He does not use alcohol or tobacco and has no history of cancer in the family.  He works as an air traffic controller at a busy airport.  Upper gastrointestinal endoscopy shows an ulcer in the distal duodenum.  Fasting serum gastrin concentration is at the upper limit of normal and rises in response to intravenous secretin.  This patient's condition is most likely caused by which of the following processes?

Quizplus · Accepted Answer

11ec160b_3967_3878_9249_d14cc616faa9_MD0001_00 This patient's distal duodenal ulcer and high-normal gastrin levels that rise in response to secretin administration are suggestive of Zollinger-Ellison syndrome (ZES). This condition is caused by gastrin-secreting tumors (gastrinomas) that are often malignant and usually located in the small intestine or pancreas. Gastrin causes parietal cell hyperplasia and stimulates gastric acid secretion, resulting in the development of peptic ulcers, heartburn, and diarrhea (excess gastric acid impairs intestinal epithelial cells and digestive enzymes). Although most proximal duodenal ulcers are caused by Helicobacter pylori infection or nonsteroidal anti-inflammatory drug (NSAID) use (Choice E), ulcers found beyond the duodenal bulb suggest ZES. Secretin is a hormone released from the duodenum in response to acid and fat in the small intestine. The hormone increases pancreatic bicarbonate secretion and inhibits the release of gastrin from normal gastric G cells. However, secretin paradoxically stimulates gastrin release from gastrinomas due to abnormal adenylate cyclase activation. As such, secretin administration can be used to differentiate ZES from other causes of hypergastrinemia (eg, atrophic gastritis). (Choice A) Autoimmune gastritis (chronic atrophic gastritis) involves the body/fundus of the stomach with antral sparing. CD4⁺ T cell-mediated parietal cell destruction causes impaired gastric acid and intrinsic factor secretion, resulting in achlorhydria and pernicious anemia, respectively. Low acid levels stimulate gastrin release from G cells (hypergastrinemia), but secretin administration causes a reduction in gastrin levels. (Choice B) H pylori infection is associated with chronic antral-predominant gastritis, which may lead to a reduction in somatostatin-producing cells (delta cells). Lack of inhibition by somatostatin allows for excessive gastrin release, which promotes gastric acid hypersecretion and proximal duodenal ulcer formation. Secretin administration typically causes a reduction in gastrin levels in these patients. (Choice C) Crohn disease is associated with dysregulation of the mucosal immune response, intestinal epithelial dysfunction, and altered composition of gut flora. Patients characteristically have linear ulcerations with adjacent normal-appearing mucosa (cobblestone appearance) in the small intestine. (Choice F) Stress-related mucosal disease can occur with severe physiologic stress (eg, shock, head trauma, burns), but the association between psychological stress (eg, working as an air traffic controller) and peptic ulcer formation is controversial. Nonetheless, neither form of stress would cause distal duodenal ulcers and hypergastrinemia. Educational objective: Zollinger-Ellison syndrome is caused by gastrinomas located in the small intestine/pancreas and presents with peptic ulcers (especially distal duodenal ulcers), heartburn, and diarrhea. Patients typically have elevated gastrin levels that rise in response to exogenous secretin administration. In contrast, secretin inhibits release of gastrin from normal gastric G cells. __________ References: Hypergastrinemia. (http://www.ncbi.nlm.nih.gov/pubmed/25698559)

A 55-Year-Old Man Comes to the Office Due to Intermittent