Does the widespread use of proton pump inhibitors mask, complicate and/or delay the diagnosis of Zollinger-Ellison syndrome?

Background: Proton pump inhibitors are potent acid suppressants which, at n ormal doses, can result in hypergastrinaemia in patients with idiopathic oe sophageal reflux disease and in the control of symptoms in most patients wi th gastrinomas. Therefore, their use could delay or mask the diagnosis of g astrinoma. Aim: To investigate whether the widespread use of proton pump inhibitors ma sks or complicates the diagnosis of gastrinoma. Subjects and methods: Data from two centres with different referral criteri a for suspected gastrinomas were analysed (Gastroenterology Unit, Rome, Ita ly and National Institutes of Health, Bethesda, AM, USA). The number of ref errals and the number of new patients with gastrinoma diagnosed in the year s prior to the widespread use of proton pump inhibitors (1986-1992) were co mpared with the numbers since proton pump inhibitors became widely availabl e (1993-1998). Results: The decrease in referral rate (P=0.0009) and the decrease in the a nnual rate of gastrinoma diagnosis (P=0.0020) at both centres correlated wi th the increased use of proton pump inhibitors. At the Italian centre, ther e 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, wherea s there was an increase in the rate of referral of other gastrointestinal e ndocrine 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 p eriod (P=0.0012). There was a 2.6-fold increase in the post-proton pump inh ibitor period in the percentage of referrals with a false diagnosis of gast rinoma as the cause of hypergastrinaemia (P=0.0040). Conclusions: In both referral centres, less patients have been referred wit h 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 b een released, the diagnosis of gastrinoma has been masked and will probably be delayed, with the result that patients with gastrinoma will be diagnose d at more advanced stages in their disease course.