Zollinger-Ellison Syndrome

A syndrome characterized by marked hypergastrinemia, gastric hypersecretion, and peptic ulceration caused by a gastrin-producing tumor (gastrinoma) of the pancreas or the duodenal wall.

The high output of gastrin from a gastrinoma continuously stimulates the parietal cells to produce acid. The incidence of gastrinomas is unknown, but these tumors are thought to be responsible for about 0.1 to 1% of duodenal ulcers. Onset of Zollinger-Ellison syndrome occurs between ages 30 and 50; about one third of patients with this syndrome are > 60.

Symptoms and Signs

Peptic ulcer disease and its symptoms occur in 90 to 95% of patients; symptoms can be persistent, progressive, and poorly responsive to drug treatment and surgery. Diarrhea occurs in > 30% of patients and may predate ulcer symptoms. Steatorrhea may result from inactivation of pancreatic lipase with a failure to hydrolyze intraluminal triglycerides and from a low pH in the lumen of the small intestine, which can result in insoluble bile acids with decreased formation of micelles. Typically, basal acid output is > 15 mEq/hour.

Diagnosis

Zollinger-Ellison syndrome is suggested by its characteristic clinical findings. Barium radiography can demonstrate prominent gastric rugal folds and duodenal (and occasionally jejunal) folds that may be thickened and dilated. Hypersecretion of gastric acid occurs in > 90% of patients. However, the most sensitive and specific diagnostic test is the demonstration of hypergastrinemia.

Patients with gastrinoma typically have serum gastrin levels > 150 pg/mL (> 71.6 pmol/L), with average serum gastrin levels of about 1000 pg/mL (> 477 pmol/L). Provocative tests include the secretin test (the most accurate) and the calcium test. In the secretin test, secretin 2 U/kg is administered over 30 seconds with serum gastrin levels measured 5 minutes before, immediately before, and 2 and 5 minutes after administration, then at 5-minute intervals for a total of 30 minutes. Serum gastrin levels increase by >= 200 pg/mL (>= 95.4 pmol/L), often within 2 minutes and almost universally by 10 minutes. In the calcium test, calcium gluconate infusion at 5 mg/kg/hour is given for 3 hours; serum gastrin levels are measured 30 minutes before and immediately before infusion and at 30-minute intervals thereafter for 4 hours. Serum gastrin levels typically increase by > 400 pg/mL (> 190.8 pmol/L), with maximum levels usually occurring during the final hour of calcium infusion.

Treatment

Some clinicians and investigators would suggest that surgical removal is more desirable than symptom management; cure rates with surgery approach 40%. Preoperative evaluation should include abdominal ultrasound, CT, and selective arteriography to localize gastrinomas and exclude metastases. Surgery is contraindicated in patients with unresectable metastatic disease.

For nonsurgical management, omeprazole is the drug of choice. The initial dose is usually 60 mg/day po, which is adjusted as necessary. Gastric acid production is monitored; the goal is to reduce basal acid output to < 10 mEq/hour in patients who are not surgical candidates, to < 5 mEq/hour in patients with previous gastric resection, and to < 1 mEq/hour in patients with severe gastroesophageal reflux disease (GERD).

Octreotide, a synthetic analog of somatostatin, decreases serum gastrin levels and gastric acid production, but it can be given only parenterally and has no benefit over omeprazole. Chemotherapy with streptozocin and 5-fluorouracil decreases serum gastrin levels in patients with metastatic disease but is usually reserved for patients with liver metastases to relieve symptoms.