Prior to the development of the radioimmunoassay for serum gastrin, 80% of gastrinoma patients presented with a severe ulcer diathesis, bleeding, obstruction, or perforation. Two thirds of patients had at least one operation. Currently, only 20% of patients present with severe ulcer complications, and only one third have had prior surgery [29]. H. pylori infection is not a risk factor for peptic ulceration in patients with gastrinoma [30]. In a study of 84 gastrinoma patients, the prevalence of H. pylori exposure was only 23%, 10% with active infection [30], less than the general population. The possibility of gastrinoma should be considered in all patients with peptic ulcer disease, and those with unexplained secretory diarrhea. All such patients should undergo measurement of fasting serum gastrin levels. An aggressive testing policy has been shown to be cost effective.

Diagnosis of gastrinoma syndrome depends on the demonstration of: 1) elevated serum gastrin levels; 2) a positive secretin stimulation test; and 3) gastric acid hypersecretion. Hypergastrinemia in the absence of increased acid production is not due to gastrinoma. It is vital to stop H2 blockers, proton pump inhibitors, and octreotide at least 24 hours before performing these tests for gastrinoma. (Assay available at Inter Science Institute-800-255-2873).

Serum gastrin levels are usually greater than 150 pg/ml in patients with gastrinoma syndrome. The exception is a small fraction of patients who secrete a biologically active variant not recognized by the antiserum used for the assay[31]. A careful history and physical is required, as gastrin levels may be elevated for a variety of other reasons (table 1). Measurement of gastric pH is also useful, because in the absence of antisecretory drugs, a pH of 3.0 or higher excludes Zollinger-Ellison Syndrome.

Establishment of the presence of gastric acid hypersecretion should include measurements of volume as well as basal and pentagastrin-stimulated acid secretion. The diagnosis is confirmed if: a) the volume of gastric secretion is large, typically greater than 10 liters per 24 hours; b) the basal acid output is over 15 mmol/h. Values in the 10-15 range are borderline, and less than 10 mmol/h exclude diagnosis of Zollinger-Ellison Syndrome. In patients who have previously undergone vagotomy, basal acid output in gastrinoma is over 3 mmol/h; c) the ratio of basal acid output to maximal pentagastrin stimulated acid output is greater than 0.6.

The most accurate and sensitive test remains the Secretin Stimulation test for gastrin secretion. No new test has emerged with a greater sensitivity or specificity. Secretin, 2 mcg/kg is given intravenously, and blood samples for gastrin are drawn at 2, 5, 10, 20, and 30 minutes. A rise of more than 100 pg/ml is strongly suggestive of Zollinger-Ellison Syndrome. False positive results are rare, and are usually found in hypochlorhydric states [32].

Mention must be made of the G-cell (gastrin cell) hyperplasia syndrome, which can be sometimes confused with the gastrinoma syndrome. Patients with G-cell hyperplasia typically have an equivocal response to secretin stimulation, and an exaggerated response to food ingestion, thus distinguishing them from patients with gastrinoma [24].

The possibly of gastrinoma should be considered in all patients with Multiple Endocrine Neoplasia type I, since 50-60% of such patients will develop gastrinoma. Patients with hyperparathyroidism should also be screened for gastrinoma, since up to 38% of patients will be found to have gastrinoma [19, 33, 34].