Hypergastrinemia

Prolonged hypergastrinemia leading to the development of colonic polyps and potentially adenocarcinoma in rats was a concern that has proven to be unfounded with long-term use in humans.19 The FDA has stated that there is insufficient evidence linking PPI use to atrophic gastritis, intestinal metaplasia, or gastric cancer.20... 

HP infection causes gastritis in all infected individuals and is causally linked to PUD. However, only about 20% of infected persons develop symptomatic PUD. Most non-NSAID ulcers are infected with HP, and HP eradication markedly decreases ulcer recurrence. HP may cause ulcers by direct mucosal damage, altering the immune/inflammatory response, and by hypergastrinemia leading to increased acid secretion. 

The prodrugs are unstable in the presence of acid and therefore must be administered as an enteric-coated preparation or as a buffered suspension. Pantoprazole is also available in an intravenous formulation. The most commonly reported side effects are diarrhea and headache. Hypergastrinemia has been noted as a reaction to the marked reduction in acid secretion. Gastric carcinoid tumors have developed in rats but not in mice or in human volunteers, even after long-term use. 

A scheme illustrating the possible mechanisms by which N -methylhistamine produced by H.p. may influence parietal cell function is shown in Figure 3. This scheme clearly shows that N -methylhistamine produced by H.p. could change the regulation of acid secretion in two opposite ways its effect on histamine formation in the fundus could reduce acid secretion, whereas the effect on somatostatin in the antrum could induce hypergastrinemia and thus increase acid secretion One could speculate that the final effect of this bacterium on acid production would depend on its distribution in the stomach. 

Mably TA, Theobald HM, Ingall GB, et al. 1990. Hypergastrinemia is associated with decreased gastric acid secretion in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats. Toxicol Appl Pharmacol 106 518-528. 

Moderate nausea, diarrhea, or abdominal pain can occur in patients taking omeprazole (13). There is an increased incidence of the severe interstitial and atrophic forms of gastritis, associated with moderate hypergastrinemia and hjrperplasia of the argyrophil cells (1). This is not necessarily an adverse effect it could represent the natural history of chronic gastritis associated with peptic ulcer disease. 

Hypergastrinemia and other gastrointestinal disorders Pulmonary disease... 

Elevated concentrations of calcitonin or increased responsiveness to stimulation have also been reported in acute and chronic renal failure, hypercalcemia, hypergastrinemia and other gastrointestinal disorders, pulmonary disease, and severe iUness. ... 

The proton pump inhibitors are usually well tolerated however, potential adverse effects include headache, dizziness, somnolence, diarrhea, constipation, and nausea. The frequency of adverse events appears to be similar to that seen with the H2-receptor antagonists. Concern and controversy regarding the safety of therapy with a proton pump inhibitor are based on the proton pump inhibitor s ability to cause hypergastrinemia and gastric carcinoid tumors in rats. After nearly a decade of experience with the proton pump inhibitors, gastric carcinoid tumors have not been directly linked to omeprazole use in humans. ... 

A number of bacterial and host factors contribute to the ability of HP to cause gastroduodenal mucosal injury. Pathogenic mechanisms include (a) direct mucosal damage, (b) alterations in the host immune/inflammatory response, and (c) hypergastrinemia leading to increased acid secretion. In addition, HP enhances the carcinogenic conversion of susceptible gastric epithelial cells. ... 

FIGURE 33-6. The gastrin hypothesis suggests that prolonged hypergastrinemia results in hyperplasia of the enterochromaffin-l ike (ECL) cells of the gastric fundus. The trophic influence of gastrin may be a risk factor for ECL cell carcinoid tumor formation. 

Synaptophysin and chromogranin A also highlight the proliferation of ECL cells in the oxyntic (fundic/body) mucosa in hypergastrinemia, hypochlorhydria, and Zollinger-Ellison syndrome. 

Hypergastrinemia is more frequent and more severe with proton-pump inhibitors than with H2-receptor antagonists, and gastrin levels of >500 ng/L occur in approximately 5 to 10% of users with chronic omeprazole administration. This hypersecretion may predispose patients to rebound hypersecretion of gastric acid upon discontinuation of therapy. 

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