A prospective evaluation of the effect of chronic proton pump inhibitor use on plasma biomarker levels in humans.

OBJECTIVE Proton pump inhibitors (PPIs) are used primarily to treat gastroesophageal reflux disease. Proton pump inhibitor-induced achlorhydria increases circulating gastrin and chromogranin A (CGA). Chromogranin is a widely used biomarker for the diagnosis and follow-up for gut-based neuroendocrine tumors (NETs). Proton pump inhibitor-induced increases in CGA or gastrin may falsely suggest the presence of a NET when none exists. Pancreastatin, a fragment of CGA, is also commonly used to diagnose and follow NETs. We hypothesized that chronic PPI use would increase circulating plasma gastrin, CGA, and pancreastatin levels. METHODS Thirty patients who used PPIs for 6 months or more (mean ± SD duration, 3.1 ± 2.5 years) and a separate control group of 30 patients who never used antacid medications were prospectively evaluated with plasma gastrin, CGA, and pancreastatin determinations. RESULTS Chronic PPI use resulted in significant increases in CGA (15.1 ± 11 vs 131 ± 207 ng/mL; P = 0.005) and significant increases in gastrin (34.8 ± 22.3 vs 167.8 ± 136.2 pg/mL; P = 0.001) compared to controls. In contrast, pancreastatin level in nonusers and chronic PPI users were identical (81.6 ± 36.4 vs 89.4 ± 43.4 pg/mL; P = 0.46). CONCLUSIONS Pancreastatin levels do not change with chronic PPI use and normal pancreastatin levels may be used to distinguish between drug-induced changes in biomarkers and tumor-related increases in circulating biomarkers.