Use of omeprazole in Zollinger‐Ellison syndrome: a prospective nine‐year study of efficacy and safety

Abstract

SUMMARY H+, K+‐ATPase inhibitors such as omeprazole are the antisecretory agents of choice for the management of gastric acid hypersecretory states, including the Zollinger‐Ellison syndrome. However, long‐term follow‐up data on the overall efficacy and safety of these agents in large numbers of patients are lacking. In the current study we examined the long‐term efficacy and safety of omeprazole in 116 patients with Zollinger‐Ellison syndrome treated with oral omeprazole at a single centre for up to 114 months (mean ± S.E.M. = 38 ± 3 months). The initial omeprazole maintenance dose was established according to the acute upward dose titration method in 89/116 patients (77%). Gastric acid output was effectively controlled using 60 mg of omeprazole once daily in 41/89 patients (46%) and 22/89 patients (25 %) required twice daily omeprazole therapy. The mean ranitidine equivalent dose for patients who required 60 mg omeprazole once daily (2.5 ± 0.2 g/day) was significantly lower than the mean ranitidine equivalent dose for patients who required more than 60 mg omeprazole once daily (4.3 ± 0.3 g/day). Long‐term omeprazole maintenance therapy was discontinued in 36/116 patients (31%) but in no cases was discontinuation due either to drug‐induced side‐effects or uncontrolled gastric acid output. Fasting serum gastrin levels were significantly elevated above pre‐treatment levels at only one time point during follow‐up and were likely due to tumour growth rather than a drug effect. The final long‐term omeprazole maintenance doses were lower than the initial doses but correlated closely with the preomeprazole basal acid output (r= 0.41, P < 0.001) and ranitidine equivalent dose requirements (r= 0.49, P < 0.001). We conclude that omeprazole effectively and safely controls gastric acid hypersecretion in all patients with Zollinger‐Ellison syndrome for up to nine years without evidence by tachyphylaxis.

Diagnosis of Zollinger–Ellison Syndrome in the Era of Ppis, Faulty Gastrin Assays, Sensitive Imaging and Limited Access to Acid Secretory Testing

“…Initially, because gastrinoma resection was rarely curative, only total gastrectomy adequately controlled the profound acid hypersecretion [17, 20, 21]. However, with the availability of histamine H 2 -antagonists in the 1980s [11, 22, 23], and later the availability of PPIs (omeprazole, lansoprazole, rabeprazole, esomeprazole, or pantoprazole) [11, 13, 24–26], medical control of acid hypersecretion, both acutely and long-term, is possible in almost every patient [11, 27, 28]. …”

Multiple endocrine neoplasia type 1 (MEN1)

“…53,72 As in sporadic gastrinoma, PPI therapy frequently controls the symptoms of hypergastrinemia and is safe to use in the long term, while H2-receptor antagonists or somatostatin analogues can be additionally used in those with persistent symptoms. 3,29,73 The role of surgery in MEN1-associated NFPNET remains unresolved, and it is recognized that progressive malignant PNET is the cause of significant mortality in MEN1. 74,75 Given that multiple non-functional pancreatic microadenomas are frequently found in patients with MEN1, and that pancreatic surgery incurs significant morbidity and mortality, a rational approach would be to aim to resect only those at high risk of progression to malignancy.…”

Gastrinoma (Duodenal and Pancreatic)

“…Patients have been treated for up to 15 years with PPIs with no evidence of tachyphylaxis and no dose-related side effects. Vitamin B 12 deficiency but not iron deficiency has been reported with long-term PPI use in ZES, but it is unclear if it causes clinically important vitamin B 12 deficiency [57,58,59]. Both intravenous PPIs (intermittent use) and continuous infusion of high doses of H2 blockers satisfactorily control acid secretion when parenteral drugs are needed.…”