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For further information, see CMDT Part 15-25: Zollinger-Ellison Syndrome (Gastrinoma)

Key Features

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

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

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 ...

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