Snapshot A 42-year-old male presents to the clinic complaining of upper abdominal pain. He reports he is under considerable stress at work and smokes a pack of cigarettes every day. The pain occurs between meals and is worse at night and often wakes him from sleep. On 1 occasion he vomited blood. Testing reveals a basal acid output (BA) of 60 mEq (normal is < 5 mEq) and a serum gastrin level of 1,000 pg/ml (normal is < 300 pg/ml). Introduction Clinical definition syndrome characterized by the secretion of gastrin by duodenal or pancreatic neuroendocrine tumors (gastrinomas) Associated conditions multiple endocrine neoplasia type 1 (MEN1) ETIOLOGY Pathogenesis excessive gastrin secretion from gastrinoma leads to high gastric acid output gastrin has trophic action on gastric parietal cells and histamine-secreting enterochromaffin-like cells high gastric acid secreting overwhelms the neutralizing capacity of pancreatic bicarbonate secretion, resulting in low pH of intestinal contents the low pH inactivates pancreatic digestive enzymes and thus interferes with the emulsification of fat by bile acids results in maldigestion and malabsorption high serum gastrin concentrations inhibit the absorption of sodium and water by the small intestine Epidemiology Demographics annual incidence is 0.5-2/million population high incidence in men compared to women Only 25% of gastrinomas arise in the pancreas with the majority occurring in the duodenum Presentation Symptoms peptic ulcer disease heartburn weight loss diarrhea Physical exam Abdominal tenderness imaging Various imaging techniques are indicated for tumor localization upper endoscopy contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) somatostatin receptor scintigraphy Endoscopic ultrasound usually indicated prior to surgical resection as it has greater sensitivity in detecting small tumors Studies Diagnostic testing diagnostic approach diagnosis is primarily based on clinical presentation (e.g., refractory peptic ulcers) studies fasting serum gastrin concentration and gastric pH best initial test serum gastrin value > 10 times the upper limit of normal (> 1,000 pg/mL) in the presence of gastric pH < 2 is diagnostic secretin stimulation test indicated in patients with elevated gastrin/low gastrin pH that are not diagnostic differentiates gastrinomas from other causes of hypergastrinemia (e.g., antral G-cell hyperplasia) patients with gastrinomas will have a dramatic rise in serum gastrin following secreting stimulation (normal gastric G cells are inhibited by secretin) calcium infusion study indicated in patients with strong clinical suspicion despite a negative secretin stimulation test MEN1 evaluation serum parathormone levels ionized calcium levels prolactin levels Differential Antral G-cell hyperplasia distinguishing factors poor response to secretin stimulation test absence of gastrinoma on imaging Treatment First-line medical management with proton pump inhibitors (e.g., omeprazole) and H2-receptor anatagonists (e.g., ranitidine) surgical resection eliminates need for antisecretory medical therapy and protects against the morbidity and mortality of metastasis Complications Stricture Perforation Metastatic gastrinoma liver is the most common site most common cause of morbidity and mortality