(Zollinger-Ellison Syndrome; Z-E Syndrome)

ByAnthony Villano, MD, Fox Chase Cancer Center
Reviewed/Revised Oct 2023
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A gastrinoma is a gastrin-producing tumor usually located in the pancreas or the duodenal wall. Gastric acid hypersecretion and aggressive, refractory peptic ulceration result (Zollinger-Ellison syndrome). Diagnosis is by measuring serum gastrin levels. Treatment is proton pump inhibitors and surgical removal.

Gastrinomas are a type of pancreatic endocrine tumor that arises from islet cells but can also arise from the gastrin-producing cells in duodenum and other sites in the body. Gastrinomas occur in the pancreas or duodenal wall 80 to 90% of the time. The remainder occur in the splenic hilum, mesentery, stomach, lymph node, or ovary. About 50% of patients have multiple tumors.

Gastrinomas usually are small (< 1 cm in diameter) and grow slowly. About 50% are malignant.

About 40 to 60% of patients with gastrinoma have multiple endocrine neoplasia, a syndrome that is associated with neuroendocrine tumors of the pancreas (eg, gastrinoma), pituitary adenomas, and parathyroid hyperplasia.

Symptoms and Signs of Gastrinoma

Zollinger-Ellison syndrome typically manifests as aggressive peptic ulcer disease, with ulcers occurring in atypical locations (up to 25% are located distal to the duodenal bulb). However, as many as 25% of patients do not have an ulcer at diagnosis. Typical ulcer symptoms and complications (eg, perforation, bleeding, obstruction) can occur. Diarrhea is the initial symptom in 25 to 40% of patients.

Diagnosis of Gastrinoma

  • Serum gastrin level

  • CT, scintigraphy, or positron emission tomography (PET) to localize

Gastrinoma is suspected by history, particularly when symptoms are refractory to standard acid suppressant therapy.

Serum gastrin level is the most reliable test. All patients have levels > 150 pg/mL (> 72 pmol/L); markedly elevated levels of > 1000 pg/mL (> 480 pmol/L) in a patient with compatible clinical features and gastric acid hypersecretion of > 15 mEq/hour establish the diagnosis. However, moderate hypergastrinemia can occur with hypochlorhydric states (eg, pernicious anemia, chronic gastritis, use of proton pump inhibitors), in renal insufficiency with decreased clearance of gastrins, in massive intestinal resection, and in pheochromocytoma.

A may be useful in patients with gastrin levels  <Helicobacter pylori infection, which commonly results in peptic ulceration and moderate excess gastrin secretion.

Treatment of Gastrinoma

  • Acid suppression

  • Surgical resection for localized disease

  • Chemotherapy for metastatic disease

Acid suppression

Proton pump inhibitors

octreotide (20 to 30 mg IM once a month) can be used.


Surgical removal should be attempted in patients without apparent metastases because of the high risk of underlying cancer. At surgery, duodenotomy and intraoperative endoscopic transillumination or ultrasonography help localize tumors.

Surgical cure is possible in 20% of patients if the gastrinoma is not part of a multiple endocrine neoplasia syndrome.


Prognosis for Gastrinoma

Five- and 10-year survival are > 90% when an isolated tumor is removed surgically vs 43% at 5 years and 25% at 10 years with incomplete removal.

Key Points

  • Most gastrinomas manifest with peptic ulcer symptoms, but some patients present with diarrhea.

  • About half of patients have multiple gastrinomas and about half have multiple endocrine neoplasia syndrome; half of gastrinomas are malignant.

  • Tumors can usually be localized with CT, somatostatin receptor scintigraphy, or positron emission tomography (PET).

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