Omeprazole, Hypergastrinemia, and Gastric Carcinoid Tumors

The long-term management of reflux esophagitis is challenging because of the frequency of symptomatic relapses and the uncertain efficacy and safety of long-term treatment with acid-suppressing drugs. Reflux esophagitis recurs within 6 months in at least 80% of patients after discontinuation of medical therapy [1]. Thus, some patients, such as those described in this issue by Klinkenberg-Knol and colleagues [2], require continuous therapy with omeprazole. Despite its superior efficacy when compared with histamine-2-(H₂) receptor antagonists in healing reflux esophagitis [3] and maintaining remissions [4], clinicians have generally been reluctant to treat patients chronically with omeprazole because of concerns about the long-term effects of omeprazole-induced hypergastrinemia. Omeprazole also is superior to H₂-receptor antagonists in healing gastric and duodenal ulcers [3] and is effective in combination with amoxicillin in eradicating Helicobacter pylori infection [5], but the hypergastrinemia associated with such short-term use appears to be of little consequence.

Because gastrin secretion by the G cells of the antral mucosa is inhibited by an acid pH in the gastric lumen, hypergastrinemia may be induced by any treatment that decreases gastric acidity. For example, the administration of H₂-receptor antagonists causes an increase in plasma gastrin levels proportional to the dose [6]. Omeprazole administration causes a greater increase because it is a more potent inhibitor of gastric acid secretion [7]. Plasma gastrin levels increase within days of starting omeprazole therapy and peak at 2 to 4 months, after which they generally remain stable at 2 to 4 times the baseline levels [2, 6-9]. …