Gastrinoma (Zollinger-Ellison syndrome)
Gastrinoma is a gastrin-secreting neuroendocrine tumor, usually arising in the duodenum or pancreas, that drives the acid hypersecretion of Zollinger-Ellison syndrome: recurrent, multiple, or refractory peptic ulcers plus diarrhea. Diagnosis rests on a markedly elevated fasting serum gastrin with a low gastric pH, then imaging to localize the tumor. First-line treatment is high-dose proton pump inhibitor therapy, with surgical resection when disease is not metastatic.
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What this article covers
- Overview
Gastrinoma is a gastrin-secreting neuroendocrine tumor, most often arising in the duodenal wall or head of the pancreas, that produces the clinical picture known as Zollinger-Ellison syndrome.
- Epidemiology
Rarity: Pancreatic neuroendocrine tumors are rare, and only 10% to 25% of them are functional (hormone-secreting).
- Risk factors
Multiple endocrine neoplasia type 1: A germline MEN1 mutation is the only established genetic risk factor, predisposing to gastrinoma along with parathyroid hyperplasia and pituitary adenoma.
- Pathophysiology
Tumor origin: Gastrinoma arises from gastrin-producing neuroendocrine cells, most often in the duodenal submucosa and less often in pancreatic islet or ductal tissue, within the gastrinoma triangle.
- Clinical features
Ulcer pattern: Recurrent, multiple, or unusually distal peptic ulcers (postbulbar duodenum or jejunum) refractory to standard-dose proton pump inhibitors and Helicobacter eradication are the hallmark presentation.
- Differential diagnosis
Helicobacter pylori-associated peptic ulcer disease: The most common cause of ulcers, but gastrin is normal or mildly elevated, and the ulcer heals after eradication rather than recurring despite it.
- Diagnosis
What establishes the diagnosis: A fasting gastrin above 1000 pg/mL with gastric pH of 2 or lower is diagnostic; a borderline gastrin requires a positive secretin stimulation test (a paradoxical rise in gastrin) to confirm.
- Management
First, start acid suppression: Begin omeprazole 60 mg orally once daily, then titrate to 40 to 120 mg/day in one to two divided doses to keep basal acid output below 10 mEq/hour; continue indefinitely unless the tumor is completely resected.
- Complications
GI bleeding: Recurrent or refractory ulcers can bleed acutely, presenting with hematemesis or melena.
- Prognosis
Malignant potential: About two-thirds of gastrinomas are malignant, and liver metastases are the single strongest predictor of poor survival.
- Prevention
Genetic testing in at-risk patients: Offer germline MEN1 mutation testing to young patients with gastrinoma or more than one endocrine tumor type, and to their first-degree relatives.
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Related articles
- Multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumor-suppressor syndrome causing parathyroid, pancreatic, and pituitary tumors, the '3 Ps.' First-line treatment is organ-specific: parathyroidectomy for hyperparathyroidism, dopamine agonists for prolactinoma, and surgical resection or acid suppression for pancreatic neuroendocrine tumors.
- Pancreatic neuroendocrine tumors (PanNETs)
Pancreatic neuroendocrine tumors (PanNETs) are islet-cell tumors that may be functional, producing a hormone-excess syndrome such as insulinoma or gastrinoma, or nonfunctioning and detected by mass effect or incidentally. First-line treatment is surgical resection when localized, with somatostatin analogues and acid suppression used to control hormone-excess symptoms before or in place of surgery.
- Peptic ulcer disease
Peptic ulcer disease is a mucosal break in the stomach or duodenum caused chiefly by Helicobacter pylori infection or NSAID use, diagnosed by upper endoscopy with biopsy of gastric ulcers to exclude malignancy. Treatment eradicates H. pylori when present, stops the ulcerogenic drug, and heals the ulcer with a proton pump inhibitor, while its complications of bleeding, perforation, and obstruction drive most of its morbidity.
- Carcinoid syndrome
Carcinoid syndrome is the clinical syndrome of episodic flushing, secretory diarrhea, and late right-sided valvular heart disease caused by serotonin and other vasoactive amines escaping hepatic first-pass metabolism, almost always because a well-differentiated neuroendocrine tumor has spread to the liver or arises outside the portal circulation. Diagnosis rests on an elevated 24-hour urinary 5-HIAA with tumor localization by somatostatin-receptor PET, and management combines somatostatin analogues for symptom control and antiproliferative effect with tumor-directed therapy and peri-procedural crisis prevention.
- Well-differentiated neuroendocrine tumors
Well-differentiated neuroendocrine tumors (formerly carcinoid tumors) arise from enterochromaffin and islet-type cells of the gut and pancreas, are graded G1 to G3 by Ki-67 and mitotic count, and may be functional (gastrinoma, insulinoma, glucagonoma, VIPoma, somatostatinoma, or carcinoid syndrome) or nonfunctional. Diagnosis rests on biopsy with neuroendocrine markers plus Ki-67 grading and somatostatin-receptor imaging, and management ranges from surgical resection to somatostatin analogues, peptide receptor radionuclide therapy, and targeted agents.
- Von Hippel-Lindau disease
Von Hippel-Lindau disease is an autosomal dominant tumor-suppressor syndrome in which loss of functional pVHL causes accumulation of hypoxia-inducible factor and a lifelong predisposition to hemangioblastomas, clear-cell renal cell carcinoma, pheochromocytoma, and pancreatic cysts and neuroendocrine tumors. Diagnosis is clinical or by VHL germline testing, and management is a lifelong, age-staged surveillance program combined with nephron-sparing or HIF-2 alpha-directed treatment of lesions as they arise.