title: Does the widespread use of proton pump inhibitors mask, complicate and/or delay the diagnosis of Zollinger-Ellison syndrome?
abstract: BACKGROUND
  Proton pump inhibitors are potent acid suppressants which, at normal doses, can result in hypergastrinaemia in patients with idiopathic oesophageal reflux disease and in the control of symptoms in most patients with gastrinomas. Therefore, their use could delay or mask the diagnosis of gastrinoma.
  
  
  OBJECTIVE
  To investigate whether the widespread use of proton pump inhibitors masks or complicates the diagnosis of gastrinoma.
  
  
  METHODS
  Data from two centres with different referral criteria for suspected gastrinomas were analysed (Gastroenterology Unit, Rome, Italy and National Institutes of Health, Bethesda, MD, USA). The number of referrals and the number of new patients with gastrinoma diagnosed in the years prior to the widespread use of proton pump inhibitors (1986-1992) were compared with the numbers since proton pump inhibitors became widely available (1993-1998).
  
  
  RESULTS
  The decrease in referral rate (P=0.0009) and the decrease in the annual rate of gastrinoma diagnosis (P=0.0020) at both centres correlated with the increased use of proton pump inhibitors. At the Italian centre, there was a 62% decrease in annual referrals (P < 0.0001) in the post-proton pump inhibitor period, relative to the pre-proton pump inhibitor period, whereas there was an increase in the rate of referral of other gastrointestinal endocrine tumours. The number of new cases of gastrinoma diagnosed decreased by 40%. At the US centre, the referral rate decreased by 28% (P=0.024) in the post-proton pump inhibitor period. There was also a 43% decrease in the number of new cases diagnosed annually in the post-proton pump inhibitor period (P=0.0012). There was a 2.6-fold increase in the post-proton pump inhibitor period in the percentage of referrals with a false diagnosis of gastrinoma as the cause of hypergastrinaemia (P=0.0040).
  
  
  CONCLUSIONS
  In both referral centres, less patients have been referred with a possible diagnosis of gastrinoma and fewer new patients with gastrinoma have been diagnosed since proton pump inhibitors became widely available. These data support the conclusion that, since proton pump inhibitors have been released, the diagnosis of gastrinoma has been masked and will probably be delayed, with the result that patients with gastrinoma will be diagnosed at more advanced stages in their disease course.
authors.affiliation: Gastroenterology Unit, Departments of Cellular Biotechnology and Haematology, University La Sapienza, Rome, Italy.
authors.forename: V D
authors.initials: VD
authors.lastname: Corleto
authors.forename: B
authors.initials: B
authors.lastname: Annibale
authors.forename: F
authors.initials: F
authors.lastname: Gibril
authors.forename: S
authors.initials: S
authors.lastname: Angeletti
authors.forename: J
authors.initials: J
authors.lastname: Serrano
authors.forename: D J
authors.initials: DJ
authors.lastname: Venzon
authors.forename: G
authors.initials: G
authors.lastname: Delle Fave
authors.forename: R T
authors.initials: RT
authors.lastname: Jensen
mesh_terms: D000897:Anti-Ulcer Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003365:Costs and Cost Analysis; D006635:Histamine H2 Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007558:Italy; D009853:Omeprazole / Q000009:adverse effects* / Q000627:therapeutic use; D054328:Proton Pump Inhibitors; D012017:Referral and Consultation; D014481:United States; D015043:Zollinger-Ellison Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology
chemical_list: D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors; D009853:Omeprazole