Interpretation

Achlorhydria is the most common cause of elevated serum gastrin levels. The most common cause for achlorhydria is treatment of gastroduodenal ulcers, nonulcer dyspepsia, or gastroesophageal reflux with proton pump inhibitors (substituted benzimidazoles, eg, omeprazole). Other causes of hypo- and achlorhydria include chronic atrophic gastritis with or without pernicious anemia, gastric ulcer, gastric carcinoma, and previous surgical or traumatic vagotomy.

If serum B12 levels are significantly low (<150 ng/L), even if the intrinsic factor blocking antibody tests are negative, a serum gastrin level above the reference range makes it likely the patient is suffering from pernicious anemia.

Hypergastrinemia with normal or increased gastric acid secretion is suspicious of a gastrinoma (Zollinger-Ellison syndrome). Gastrin levels less than 100 pg/mL are observed so uncommonly in untreated gastrinoma patients with intact upper gastrointestinal anatomy as to virtually exclude the diagnosis. The majority (>60%) of patients with gastrinoma have very significantly elevated serum gastrin levels (>400 pg/mL). Levels above 1000 pg/mL in a gastric- or duodenal-ulcer patient without previous gastric surgery, on no drugs, who has a basal gastric acid output of greater than 15 mmol/hour (>5 mmol/hour in patients with prior acid-reducing surgery) are considered diagnostic of gastrinoma. If there are any doubts about gastric acid output, an infusion of 0.1 M HCl (hydrochloric acid) into the stomach reduces the serum gastrin in patients with achlorhydria but not in those with gastrinoma.

Other conditions that may be associated with hypergastrinemia in the face of normal or increased gastric acid secretion include gastric and, rarely, duodenal ulcers, gastric outlet obstruction, bypassed gastric antrum, and gastric dumping. Occasionally, diabetes mellitus, autonomic neuropathy with gastroparesis, pheochromocytoma, rheumatoid arthritis, thyrotoxicosis, and paraneoplastic syndromes can also result in hypergastrinemia with normal acid secretion. None of these conditions tends to be associated with fasting serum gastrin levels above 400 pg/mL, and levels above 1000 pg/mL are virtually never observed.

Several provocative tests can be used to distinguish these patients from individuals with gastrinomas. Patients with gastrinoma, who have normal or only mildly to modestly increased fasting serum gastrin levels, respond with exaggerated serum gastrin increases to intravenous infusions of secretin or calcium. Because of its greater safety, secretin infusion is preferred. The best validated protocol calls for a baseline fasting gastrin measurement, followed by an injection of 2 clinical units of secretin per kg body weight (0.4 microgram/kg) over 1 minute and further serum gastrin specimens at 5-, 10-, 15-, 20-, and 30-minutes postinjection. A peak gastrin increase of more than 200 pg/mL above the baseline value has greater than 85% sensitivity and near 100% specificity for gastrinoma. Secretin or calcium infusion tests are not carried out in the clinical laboratory but are usually performed at gastroenterology or endocrine testing units under the supervision of a physician. They are progressively being replaced (or supplemented) by imaging procedures, particularly duodenal and pancreatic endoscopic ultrasound.

All patients with confirmed gastrinoma should be evaluated for possible multiple endocrine neoplasia type 1 (MEN 1), which is the underlying cause in approximately 25% of cases. If clinical, biochemical, or genetic testing confirms MEN 1, other family members need to be screened.