To Örebro University

Introduction: Prevalence of distant stage disease and overall mortality rates vary considerably among patients with multiple endocrine neoplasia type 1 (MEN1).

Aim(s): To study the metastatic potential of MEN1 different components, and the associated mortality rates.

Materials and methods: We included patients with clinical and/or genetic diagnosis of MEN1, followed at the Endocrinology Unit, First Department of Propaedeutic and Internal Medicine, Laiko General Hospital of Athens, Greece.

Results: We included 123 patients; 56 were women (45.9%). MEN1 first manifestation, commonly hyperparathyroidism, appeared at <25 years of age in 46 patients (38%), between 25-40 years in 49 (39,8%) and >40 years in 23 patients (19,4%). Among patients with pNETs (n=79), 23 had grade 2 and one grade 3 tumors, respectively. Fifteen patients (19%) had secretory pNETs for either insulin or gastrin. PNET distant metastases, mainly to the liver, were present in seven patients (8.9%). Overall, atypical lung (AC) and thymic carcinoids (TC) were encountered in three and seven patients, respectively (two of these had ACTH dependent Cushing’s syndrome); AC and/or TC distant metastases were encountered in all ten patients, harbouring these primaries. Overall, 12 patients with stage IV disease manifested disease progression according to RECIST criteria, with a mean duration of disease for pNETs 14 years and for AC and TC 8 years and died. The mortality was associated with the disease progression in 11 patients, and one died because of sepsis.

Conclusion: Spread metastatic disease is encountered in all MEN1-associated AC and TC tumors and in a subset of pNETs, approximately 9%. These MEN1 components account for the disease associated mortality at a 10% rate in our Greek MEN1 cohort.