Effect of Proton-Pump Inhibitor Therapy on Serum Chromogranin A Level

Background: The neuroendocrine marker, chromogranin A (CgA) increases during medium- or long-term proton-pump inhibitor (PPI) treatment. Aims: To analyze the effect of ultra-short-term and diverse dose of PPI therapy on serum CgA and gastrin levels and evaluate the effect of PPI treatment cessation. Patients and Methods: Fasting serum CgA and gastrin were determined in newly diagnosed gastroesophageal reflux disease (GERD) patients (n = 54) treated with diverse doses of PPI during a 28-day period, in patients treated with PPIs for at least 6 months (n = 42), and in subjects where PPI treatment could be stopped (n = 11). Results: A significant stepwise increase of CgA levels was observed after 5 days during the 28-day period treatment with all PPI doses. Gastrin increased significantly also in the standard and high-dose PPI subgroups. The most prominent increase of CgA was observed in the high-dose PPI subgroup. Serum CgA and gastrin were markedly elevated after 6 months of PPI treatment, and decreased significantly after 5 days of PPI discontinuation. Conclusions: Serum CgA increases significantly even after ultra-short-term (5 days) PPI therapy. After long-term treatment, 5-day cessation of PPI therapy is sufficient to decrease significantly both CgA and gastrin levels.

[1]  W. Jeske,et al.  Commentary to “Chromogranin A: Biological Function and Clinical Utility in Neuroendocrine Tumor Disease” , 2010, Annals of surgical oncology.

[2]  I. Modlin,et al.  Chromogranin A—Biological Function and Clinical Utility in Neuro Endocrine Tumor Disease , 2010, Annals of Surgical Oncology.

[3]  P. Moayyedi,et al.  Medical treatments for the maintenance therapy of reflux oesophagitis and endoscopic negative reflux disease. , 2010, The Cochrane database of systematic reviews.

[4]  C. Reimer,et al.  Clinical trial: long‐term use of proton pump inhibitors in primary care patients – a cross sectional analysis of 901 patients , 2009, Alimentary pharmacology & therapeutics.

[5]  C. Reimer,et al.  Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. , 2009, Gastroenterology.

[6]  Z. Tulassay,et al.  Peptic Esophageal Stricture: Medical Treatment , 2009, Digestive Diseases.

[7]  P. Orosz,et al.  Gastroesophageal Reflux Disease: Work-Related Disease? , 2009, Digestive Diseases.

[8]  P. Igaz,et al.  Serum chromogranin A reflects regression of metastatic carcinoid during prolonged octreotide treatment. , 2009, European journal of gastroenterology & hepatology.

[9]  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.

[10]  G. Qvigstad,et al.  Serum gastrin and chromogranin A levels in patients with fundic gland polyps caused by long-term proton-pump inhibition , 2008, Scandinavian journal of gastroenterology.

[11]  B. Hirschowitz,et al.  Chromogranin A in patients with acid hypersecretion and/or hypergastrinaemia , 2007, Alimentary pharmacology & therapeutics.

[12]  H. El‐Serag,et al.  Temporal trends in new and recurrent oesophageal strictures in a Medicare population , 2007, Alimentary pharmacology & therapeutics.

[13]  G. Cui,et al.  Physiological and clinical significance of enterochromaffin-like cell activation in the regulation of gastric acid secretion. , 2007, World journal of gastroenterology.

[14]  P. Moayyedi,et al.  Diagnostic and Therapeutic Use of Proton Pump Inhibitors in Non-Cardiac Chest Pain: A Metaanalysis , 2005, The American Journal of Gastroenterology.

[15]  J. Zacny,et al.  Systematic review: the efficacy of intermittent and on‐demand therapy with histamine H2‐receptor antagonists or proton pump inhibitors for gastro‐oesophageal reflux disease patients , 2005, Alimentary pharmacology & therapeutics.

[16]  D. Conte,et al.  Plasma chromogranin A in patients with autoimmune chronic atrophic gastritis, enterochromaffin-like cell lesions and gastric carcinoids. , 2005, European journal of endocrinology.

[17]  J. Sen,et al.  Chromogranin A, a Marker of the Therapeutic Success of Resection of Neuroendocrine Liver Metastases: Preliminary Report , 2004, World Journal of Surgery.

[18]  E. van Marck,et al.  Neuroendocrine tumor markers and enterochromaffin-like cell hyper/dysplasia in type 1 diabetes. , 2004, Diabetes care.

[19]  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.

[20]  G. Qvigstad,et al.  Hypergastrinemia in animals and man: causes and consequences , 2004, Scandinavian journal of gastroenterology.

[21]  M. Stridsberg,et al.  A comparison between three commercial kits for chromogranin A measurements. , 2003, The Journal of endocrinology.

[22]  R. Jensen,et al.  Involvement of cholecystokinin/gastrin-related peptides and their receptors in clinical gastrointestinal disorders. , 2002, Pharmacology & toxicology.

[23]  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.

[24]  D. O'Connor,et al.  Malignant Pheochromocytoma: Chromaffin Granule Transmitters and Response to Treatment , 2000, Hypertension.

[25]  A. Kjellin,et al.  Omeprazole and CYP2C19 polymorphism: effects of long‐term treatment on gastrin, pepsinogen I, and chromogranin A in patients with acid related disorders , 2000, Alimentary pharmacology & therapeutics.

[26]  Jonkers,et al.  Serum gastrin and chromogranin A during medium‐ and long‐term acid suppressive therapy: a case‐control study , 1999, Alimentary pharmacology & therapeutics.

[27]  J. Rehfeld,et al.  Basal chromogranin A and gastrin concentrations in circulation correlate to endocrine cell proliferation in type-A gastritis. , 1997, Scandinavian journal of gastroenterology.

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

[29]  J. Jansen,et al.  Long-Term Treatment with Omeprazole for Refractory Reflux Esophagitis: Efficacy and Safety , 1994, Annals of Internal Medicine.

[30]  A. Sandvik,et al.  Gastrin-histamine sequence in the regulation of gastric acid secretion. , 1991, Gut.

[31]  G. Dockray,et al.  Gastrin: old hormone, new functions , 2004, Pflügers Archiv.

[32]  J. C. Tony The chromogranin-secretogranin family. , 2003, The New England journal of medicine.

[33]  A. Oluwasanmi,et al.  Gastro-oesophageal reflux disease. , 1999, Hospital medicine.