Serum gastrin and chromogranin A during medium- and long-term acid suppressive therapy: a case-control study

Background: Serum chromogranin A (CgA) is regarded as a reliable marker of neuroendocrine proliferation. We previously described increased serum CgA l evels during short-term profound gastric acid inhibition. Aim: To investigate serum gastrin and CgA levels in dyspeptic patients duri ng continuous medium- (6 weeks to 1 year), or long-term (1-8 years) gastric acid suppressive therapy, Patients and methods: 114 consecutive dyspeptic patients referred for upper gastrointestinal endoscopy were enrolled in a cross-sectional, case-contro l study [62 patients on continuous antisecretory therapy, either with proto n pump inhibitors (n = 47) or H-2-receptor antagonists (H(2)RA) (n = 15) fo r gastro-oesophageal reflux disease with or without Barrett's oesophagus or functional dyspepsia, and 52 age- and sex-matched patients without medical acid inhibition and with normal endoscopic findings (control group)]. Omep razole doses ranged from 20 mg to 80 mg daily and ranitidine from 150 mg to 450 mg daily, Fasting serum CgA and serum gastrin levels were measured by radioimmunoassay (reference values: serum CgA < 4.0 nmol/L; serum gastrin < 85 ng/L), Results: Fasting serum CgA levels positively correlated with serum gastrin in the entire study population (r = 0.55, P = 0.0001), Median serum CgA val ues were higher in patients treated with a proton pump inhibitor than H(2)R A [2.8 (2.0-5.9) nmol/L vs. 2 (1.9-2.3) nmol/L, P < 0.002] and controls [2. 8 (2.0-5.9) nmol/L vs. 1.8 (1.5-2.2) nmol/L, P < 0.0001) and did not differ between patients treated with H(2)RA or controls. Serum gastrin and CgA le vels in patients on proton pump inhibitor therapy positively correlated wit h the degree and duration of acid inhibition. Patients on long-term proton pump inhibitor therapy had significantly higher fasting serum gastrin and C gA than those on medium-term proton pump inhibitor therapy [127 (73-217) ng /L vs. 49 (29-78) ng/L, P < 0.0001 and 4.8 (2.8-8) ng/L vs. 2.1 (1.9-2.6) n g/L, P < 0.001]. No such relation was found in patients on medium- vs. long -term H(2)RA. Overall, patients with positive Helicobacter pylori serology had higher serum gastrin and CgA levels than those with negative H. pylori serology [51 (27-119) ng/L vs. 27 (14-79) ng/L, P = 0.01, 2.4 (1.9-3.4) nmo l/L vs, 2.0 (1.7-2.5) nmol/L, P = 0.05]. Conclusions: During long-term continuous proton pump inhibitor treatment, s erum gastrin and CgA levels are significantly elevated compared to H(2)RA t reatment and nontreated dyspeptic controls. H. pylori infection seems to af fect gastric ECL cell secretory function. Increased serum CgA values during longterm profound gastric acid inhibition could reflect either gastric ent erochromaffin-like cell hyperfunction or proliferative changes.