Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 15-25: Zollinger-Ellison Syndrome (Gastrinoma) + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Peptic ulcer disease, may be severe and atypical Gastric acid hypersecretion Diarrhea common, relieved by nasogastric suction Most cases are sporadic; 25% with multiple endocrine neoplasia (MEN) type 1 +++ General Considerations ++ Caused by gastrin-secreting gut neuroendocrine tumors (gastrinomas), which result in hypergastrinemia and acid hypersecretion Gastrinomas cause < 1% of peptic ulcers Primary gastrinomas may arise in the pancreas (25%), duodenal wall (45%), lymph nodes (5–15%), or other locations (20%) Most gastrinomas are solitary or multifocal nodules that are potentially resectable; 25% are small multicentric gastrinomas associated with MEN 1 that are more difficult to resect Gastrinomas are malignant in less than two-thirds; one-third have already metastasized to the liver at initial presentation Screening for Zollinger-Ellison syndrome with fasting gastrin levels indicated for patients with Ulcers refractory to standard therapies Giant ulcers (> 2 cm) Ulcers located distal to the duodenal bulb Multiple duodenal ulcers Frequent ulcer recurrences Ulcers associated with diarrhea Ulcers occurring after ulcer surgery Ulcers with complications Ulcers with hypercalcemia Family history of ulcers Ulcers not related to Helicobacter pylori or nonsteroidal anti-inflammatory drugs (NSAIDs) + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Peptic ulcers in > 90%, usually solitary and in proximal duodenal bulb, but may be multiple or in distal duodenum Isolated gastric ulcers do not occur Gastroesophageal reflux symptoms Diarrhea, steatorrhea, and weight loss secondary to pancreatic enzyme inactivation +++ Differential Diagnosis ++ Peptic ulcer disease due to other cause, eg, NSAIDs, H pylori Gastroesophageal reflux disease, esophagitis, gastritis, pancreatitis, or cholecystitis Diarrhea due to other cause Other gut neuroendocrine tumor Carcinoid Insulinoma VIPoma Glucagonoma Somatostatinoma Hypergastrinemia due to other cause Pernicious anemia Gastric outlet obstruction Vagotomy Chronic kidney disease + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Fasting serum gastrin concentration increased (> 150 pg/mL [> 150 ng/L]) in patients not taking H2-receptor antagonists for 24 h or proton pump inhibitor for 6 days Serum calcium, parathyroid hormone, prolactin, leutinizing hormone, follicle-stimulating hormone, and growth hormone level in all patients with Zollinger-Ellison syndrome to exclude MEN 1 Gastric pH of > 3.0 implies hypochlorhydria and excludes gastrinoma +++ Imaging Studies ++ CT and MRI scans Commonly obtained to look for large hepatic metastases and primary lesions However, they have low sensitivity for small lesions Somatostatin receptor scintigraphy (SRS) with SPECT has high sensitivity (> 80%) for detecting hepatic metastases, as well as primary tumors Endoscopic ultrasonography (EUS) Indicated in patients with negative SRS May be useful to detect small gastrinomas in the duodenal wall, pancreas, or peripancreatic lymph nodes Combination of SRS and EUS can localize > 90% of primary gastrinomas preoperatively +++ Diagnostic Procedures ++ Secretin stimulation test distinguishes Zollinger-Ellison syndrome from other causes of hypergastrinemia Secretin, 2 units/kg intravenously, produces a rise in serum gastrin of > 200 pg/mL (200 ng/L) within 2–30 min in 85% of patients with gastrinoma + Treatment Download Section PDF Listen +++ +++ Medications ++ Proton pump inhibitors (omeprazole, rabeprazole, pantoprazole, esomeprazole, or lansoprazole), 40–120 mg/day, titrated to achieve a basal acid output of < 10 mEq/h for metastatic disease +++ Surgery ++ Primary resection of gastrinoma at laparotomy for localized disease Preoperative studies, duodenotomy with careful duodenal inspection, and intraoperative palpation and sonography allow successful localization and resection in the majority of cases Surgical resection of isolated hepatic metastases + Outcome Download Section PDF Listen +++ +++ Complications ++ In patients with unresectable disease, complications of gastric acid hypersecretion can be prevented in almost all cases by sufficient doses of proton pump inhibitors Treatment options for metastatic disease include interferon, octreotide, combination therapy, and chemoembolization +++ Prognosis ++ 15-year survival of patients without liver metastases at initial presentation is > 95% 10-year survival of patients with hepatic metastases is 30% +++ When to Refer ++ All patients with Zollinger-Ellison syndrome should be referred to a gastrointestinal surgeon with expertise in evaluation and management + References Download Section PDF Listen +++ + +De Angelis C et al. Diagnosis and management of Zollinger-Ellison syndrome in 2017. Minerva Endocrinol. 2018 Jun;43(2):212–20. [PubMed: 28949124] + +Guarnotta V et al; NIKE group. The Zollinger-Ellison syndrome: is there a role for somatostatin analogues in the treatment of the gastrinoma? Endocrine. 2018 Apr;60(1):15–27. [PubMed: 29019150] + +Norton JA et al. Gastrinomas: medical or surgical treatment. Endocrinol Metab Clin North Am. 2018 Sep;47(3):577–601. [PubMed: 30098717] + +Singh Ospina N et al. Assessing for multiple endocrine neoplasia type 1 in patients evaluated for Zollinger-Ellison Syndrome—clues to a safer diagnostic process. Am J Med. 2017 May;130(5):603–5. [PubMed: 28011308]