Context: MEN1 patients frequently develop Zollinger-Ellision syndrome (MEN1/ZES). Although esophageal reflux symptoms are common in these patients, little is known about long-term occurrence of severe peptic esophageal disease including strictures and Barrett's esophagus (BE).

Objective: To prospectively analyze the frequency of severe peptic esophageal disease in ZES patients with/without MEN1.

Setting: Tertiary care research-center.

Patients: 295 patients (80 = MEN1/ZES, 215 = sporadic ZES) participating in a prospective study.

Interventions-outcome measures: Assessment of MEN1, acid hypersecretion, UGI endoscopy/biopses and tumor status initially and at each follow-up. Esophageal manometry was performed in 89 patients. Frequency/type of esophageal disease was correlated with clinical/laboratory/tumoral features of ZES/MEN1.

Results: In MEN1/ZES patients esophageal stricture was 3-fold higher, BE 5-fold higher, dysplasia 8-fold higher and one patient died of esophageal adenocarcinoma. Esophageal symptoms were more frequent/severe in MEN1/ZES, but known risk factors for severe esophageal disease and ZES specific features did not differ between MEN1/ZES and sporadic ZES. In MEN1/ZES the onset of ZES was 10 yr earlier, H₂-antagonists were used longer and at lower doses. MEN1/ZES patients with esophageal disease differed from those without in that ZES diagnosis was delayed longer, esophageal symptoms were more frequent/severe, hiatal hernias were more frequent, esophagitis/pyloric scarring were more common, BAO was higher and hyperparathyroidism was underdiagnosed.

Conclusions: This study shows MEN1/ZES patients have a higher incidence of severe esophageal disease including the premalignant condition BE and identifies factors important for their pathogenesis that need to be incorporated into their long-term treatment.