pancreastatin and Gastroesophageal-Reflux

Drugs inhibiting gastric acid secretion are widely used because of the high prevalence of acid-related disorders. However, from clinical experience it seems that symptom relapse is common after withdrawal of these drugs. Experimental as well as clinical studies have demonstrated an increased acid secretion after a period of treatment with either histamine 2 receptor antagonists or proton pump inhibitors. Rebound hypersecretion is likely to reflect the following sequence of events: Long-term inhibition of acid output is accompanied by elevated serum gastrin levels, leading to enterochromaffin-like cell activation and proliferation, resulting in increased amounts of histamine being mobilized from these cells to stimulate the parietal cells. The clinical consequences of rebound hypersecretion have not been settled.

Topics: Animals; Biomarkers; Chromogranin A; Enterochromaffin-like Cells; Gastric Acid; Gastric Mucosa; Gastrins; Gastroesophageal Reflux; Histamine; Histamine H2 Antagonists; Humans; Pancreatic Hormones; Parietal Cells, Gastric; Proton Pump Inhibitors; Receptor, Cholecystokinin B; Recurrence; Time Factors

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.. 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.. 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).. 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.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chromogranin A; Female; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Neuroendocrine Tumors; Pancreas; Pancreatic Hormones; Pancreatic Neoplasms; Prospective Studies; Proton Pump Inhibitors