Serum chromogranin A as a screening test for gastric enterochromaffin-like cell hyperplasia during acid-suppressive therapy

Eur J Clin Invest. 2001 Sep;31(9):802-11. doi: 10.1046/j.1365-2362.2001.00890.x.


Background: Serum chromogranin A (CgA), a marker of neuroendocrine neoplasia, increases during profound gastric acid inhibition, possibly reflecting the trophic effect of gastrin on the enterochromaffin-like (ECL) cells.

Aims: This study investigated the clinical value of serum CgA as a screening test for gastric fundic enterochromaffin-like (ECL) cell hyperplasia during acid-suppressive therapy.

Method: A consecutive series of 230 dyspeptic patients referred for upper gastrointestinal endoscopy was investigated in a cross-sectional design. They were 154 patients on continuous medium-term (6 weeks to one year) or long-term (longer than one year) acid inhibition with either proton pump inhibitors (PPIs, n = 117) or histamine2-receptor antagonists (H2RAs, n = 37) for gastro-oesophageal reflux disease, and 76 nontreated subjects, with normal endoscopic findings (control group). Fasting blood samples were analysed for gastrin and CgA. Gastric biopsy specimens (oxyntic mucosa) were examined for histological evaluation of gastritis (Sydney classification) and of ECL cell hyperplasia (Solcia classification).

Results: Serum CgA levels correlated positively with serum gastrin, following a quadratic function (r = 0.78, P < 0.0001). Elevated serum CgA values during long-term acid inhibition correlated with the presence and severity of fundic ECL cell hyperplasia. Multivariate analysis identified hypergastrinaemia (P < 0.0001), duration of acid inhibition (P < 0.0001), H. pylori infection (P = 0.008), ECL cell hyperplasia (P = 0.012), and body gland atrophy (P = 0.043) as independent predictors of elevated serum CgA. In subjects on long-term acid inhibition (n = 123), serum CgA was equally sensitive but more specific than serum gastrin for the detection of ECL cell hyperplasia (sensitivity, 91.3% for both; specificity, 73% vs. 43%, P < 0.0001).

Conclusions: During long-term gastric acid inhibition, serum CgA levels reflect the presence and severity of fundic ECL cell hyperplasia. Serum CgA is therefore a useful screening test for gastric ECL cell proliferative changes within this context.

MeSH terms

  • Adult
  • Aged
  • Anti-Ulcer Agents / adverse effects*
  • Chromogranin A
  • Chromogranins / blood*
  • Cross-Sectional Studies
  • Enterochromaffin-like Cells / pathology*
  • Female
  • Gastric Acid / metabolism
  • Gastric Fundus / pathology
  • Gastrins / blood
  • Gastritis / blood
  • Gastritis / drug therapy*
  • Gastritis / pathology*
  • Gastroesophageal Reflux / blood
  • Gastroesophageal Reflux / drug therapy
  • Gastroesophageal Reflux / pathology
  • Helicobacter Infections / blood
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / pathology
  • Helicobacter pylori
  • Humans
  • Hyperplasia
  • Male
  • Mass Screening
  • Middle Aged
  • Multivariate Analysis
  • Sensitivity and Specificity


  • Anti-Ulcer Agents
  • CHGA protein, human
  • Chromogranin A
  • Chromogranins
  • Gastrins