Effect of short-term proton pump inhibitor treatment and its discontinuation on chromogranin A in healthy subjects.

CONTEXT Chromogranin A (CgA) is used as a generic tumor marker for neuroendocrine tumors. Proton pump inhibitors (PPI) are known to increase CgA, but it is not clear to what extent, and there is little information on how long PPI need to be discontinued before the effect of PPI has disappeared. Furthermore, is it not known whether this PPI effect is dependent on the CgA assay used. OBJECTIVE The aim of the study was to determine the effect of 7-d treatment with a PPI and its discontinuation on CgA in serum and plasma comparing four CgA assays. DESIGN AND PARTICIPANTS Seventeen healthy subjects took lansoprazole 30 mg at bedtime for 7 d, and blood samples for CgA were obtained at baseline, d 7 of PPI use, and 1, 2, 4, and 7 d after discontinuation of the PPI. In all samples, CgA was measured using the following assays: Alpco (serum and plasma), Cis-Bio (serum and plasma), DAKO, and Cis-Bio radioisotope assay. RESULTS When using the same assay, CgA was higher in plasma than in serum. Treatment with a PPI for 1 wk resulted in a significant (about 2.5-fold) increase in CgA with significant interindividual variation. After discontinuation of PPI, serum CgA gradually declined, with a half-life of 4-5 d. CONCLUSION Short-term PPI use results in a significant increase of CgA in serum and plasma, an effect that is largely independent of the assay used. PPI need to be discontinued for 2 wk to fully eliminate their effect on CgA. This effect of PPI needs to be considered when interpreting results of CgA measurements.

[1]  T. Viset,et al.  Gastric neuroendocrine carcinoma after long-term use of proton pump inhibitor , 2012, Scandinavian journal of gastroenterology.

[2]  M. Muller,et al.  Discontinuation of proton pump inhibitors during assessment of chromogranin A levels in patients with neuroendocrine tumours , 2011, British Journal of Cancer.

[3]  M. Ducreux,et al.  Chromogranin a Measurement in Metastatic Well-Differentiated Gastroenteropancreatic Neuroendocrine Carcinoma: Screening for False Positives and a Prospective Follow-Up Study , 2011, The International journal of biological markers.

[4]  Z. Tulassay,et al.  Effect of Proton-Pump Inhibitor Therapy on Serum Chromogranin A Level , 2011, Digestion.

[5]  W. Jeske,et al.  [Chromogranin A (CgA) - the influence of various factors in vivo and in vitro, and existing disorders on it's concentration in blood]. , 2010, Endokrynologia Polska.

[6]  H. Chae,et al.  [Influence of long-term gastric acid suppression therapy on the expression of serum gastrin, chromogranin A, and ghrelin]. , 2009, The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi.

[7]  M. Spampatti,et al.  Neuroendocrine tumors of the gastro-entero-pancreatic system. , 2008, World journal of gastroenterology.

[8]  G. Qvigstad,et al.  Proton pump inhibitors and gastric neoplasia , 2007, Gut.

[9]  R. Pezzilli,et al.  Chromogranin A: is it a useful marker of neuroendocrine tumors? , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  R. Fossmark,et al.  Rebound acid hypersecretion after long‐term inhibition of gastric acid secretion , 2005, Alimentary pharmacology & therapeutics.

[11]  F. Minuto,et al.  Effect of short-term treatment with low dosages of the proton-pump inhibitor omeprazole on serum chromogranin A levels in man. , 2004, European journal of endocrinology.

[12]  D. Jonkers,et al.  Serum chromogranin A as a screening test for gastric enterochromaffin‐like cell hyperplasia during acid‐suppressive therapy , 2001, European journal of clinical investigation.

[13]  R. Bouillon,et al.  Chromogranin A: its clinical value as marker of neuroendocrine tumours , 1998, European journal of clinical investigation.

[14]  A. Sandvik,et al.  Marked increase in gastric acid secretory capacity after omeprazole treatment. , 1996, Gut.

[15]  T. Seufferlein,et al.  Gastrin transactivates the chromogranin A gene through MEK-1/ERK- and PKC-dependent phosphorylation of Sp1 and CREB. , 2008, Cellular signalling.