P213 - ECE_3504 - Epidemiological profile of 134 patients with multiple endocrine neoplasia type 1 (MEN1)

Abstract

Patients with Multiple Endocrine Neoplasia type 1 (MEN1) exhibit marked clinical heterogeneity regarding tissue involvement, metastatic potential, disease stage at diagnosis, and overall mortality. To evaluate the clinical manifestations and mortality associated with various neuroendocrine tumors (NETs) in a cohort of patients with MEN1. We conducted a retrospective analysis of 134 patients with clinical and/or genetically confirmed MEN1 followed at the ENETS–EURACAN Centre of Excellence, Laiko General Hospital, Athens. Of 134 patients, 53.5% were male and 46.5% female. The mean follow-up from diagnosis to last data collection was 14.8years. At study conclusion, 121 patients (90.3%) were alive and 13 (9.7%) had died. Genetic testing was performed in 58.9% of patients (79/134), with MEN1 mutations identified in 75 individuals, most frequently in exons 9 (22.8%), 10 (22.8%), and 3 (15.2%). The most common initial manifestation was primary hyperparathyroidism (88%), occurring before age 25 in 39.4%, between 25-40 in another 39.4%, and after age 40 in 19.2% of patients. Gastroenteropancreatic NETs (GEP-NETs) were identified in 82 patients (75.9%). Firty-eight (50%) had G1, 23 (37.5%) G2 tumors (13% of which were stage III-IV), and one G3 tumor (2.7%, stage IV). Functioning GEP-NETs occurred in 15 patients (9 gastrinomas and 6 insulinomas). Pituitary adenomas (pitNETs) were found in 67 patients (60.9%); 46 were microadenomas (57.5%) and 15 macroadenomas (18.8%). Adrenal adenomas were observed in 30 patients (28.3%): 17 were unilateral (14.2%) and 19 bilateral (15.8%). Only 30% were functioning: 26.7% secreting cortisol, followed by aldosterone (3.3%). Other neoplasias included meningiomas (11.8%), breast cancer (4.0%), and differentiated thyroid cancer (7.1%). Pulmonary NETs (LungNETs) were found in 11 patients: 8 typical carcinoids (TC),3 atypical carcinoids (AC). Thymic carcinoids (ThC) were diagnosed in 5 patients: 2 with G2 tumors developed ACTH-dependent Cushing’s syndrome. Distant metastases from GEP-NETs, occurred in 16 patients (12.9%), all with G2 tumors >2 cm, mainly hepatic. Pancreatectomy was performed in 27 patients (24.1%); 38.0% received somatostatin analogs, and 13.4% PRRT. All patients with AC and/or ThC developed metastates, and 5 died. Additionally, seven patients died due to metastatic G2 PanNETs, and one from sepsis. In one of the largest Greek MEN1 cohorts, we described the clinical phenotype, morbidity, and mortality of affected individuals. The study highlights the clinical and neoplastic heterogeneity of the syndrome and underscores the need for systematic, individualized follow-up in specialized centers with expertise in neuroendocrine tumors.