ZOLLINGER-ELLISON SYNDROME CAN BE THE INITIAL ENDOCRINE MANIFESTATIONIN PATIENTS WITH MULTIPLE ENDOCRINE NEOPLASIA-TYPE-I

PURPOSE: To determine whether patients with multiple endocrine neoplas ia type I (MEN-I) can initially present with Zollinger-Ellison syndrom e (ZES), and to learn whether ZES exhibits any distinguishing features when it occurs as a first manifestation of MEN-I. PATIENTS AND METHOD S: Sixty patients who had been referred to a clinical research center with ZES were examined by cohort analysis. Twenty-eight had MEN-I and 32 did not. In patients with MEN-I, we analyzed the temporal relations hips between the clinical and biochemical manifestations of ZES and th e other endocrinopathies associated with the neoplasia. To determine w hether patients who had ZES as a first manifestation of MEN-I (n = 8) had any distinguishing clinical characteristics, we compared them to a cohort of patients with established sporadic ZES (n = 32) matched for age, sex, and time since the onset of symptoms consistent with ZES. R ESULTS: Of the 28 patients with ZES and MEN-I, 11 initially presented with ZES and hyperparathyroidism (HP) and 1 with evidence only for pit uitary disease. Eight patients (29%) presented with features of ZES an d developed clinical and biochemical evidence for HP later, while the same number developed these 2 endocrinopathies in the opposite order. In whichever order ZES and HP occurred, the time from the diagnosis of the first to the diagnosis of the second was similar. It ranged from 9 to 177 months in patients who presented with ZES first, and from 12 to 264 months in patients who presented with HP first. At the time of initial diagnosis, the patients who presented with ZES as a manifestat ion of MEN-I had no distinguishing ZES-related symptoms, biochemical a ssays, or tumor imaging results compared to the cohort of patients who had the syndrome sporadically. CONCLUSION: Patients with MEN-I can in itially present with a symptomatic pancreatic endocrine tumor syndrome without any other disease manifestations. In patients with ZES and ME N-I, up to one third may present with ZES without evidence of any othe r endocrinopathy. Consequently, patients with presumed sporadic ZES sh ould undergo continual biochemical screening for other endocrinopathie s characteristic of MEN-I and, in the future, genetic studies for the MEN-I gene.