Endocrine Abstracts

JOINT3401

Introduction: Multiple Endocrine Neoplasia type 2 (MEN2) is a rare disease caused by activating mutations of the RET proto-oncogene. MEN2 is responsible for predisposition to develop endocrine tumors including medullary thyroid carcinoma (MTC) and pheochromocytomas (PHEO)¹. MEN2 is characterized by a genotype-phenotype correlation, as evidenced by the phenotypic differences of the two main entities: MEN2A, mainly linked to codon 634 mutations, associates CMT, PHEO, less frequently primary hyperparathyroidism, while MEN2B linked to codon 918 mutation associates CMT, PHEO and cutaneous-mucosal, digestive and bone manifestations². This genotype-phenotype correlation is the basis of international recommendations for monitoring and management (prophylactic and curative) of MEN2 patients³. Despite this genotype-phenotype correlation, MEN2 is characterized by intra- and inter-family variability for patients carrying the same RET variant, particularly concerning CMT. The aim of this study is to conduct a retrospective analysis of the clinical, biological, and genetic characteristics of MEN2 patients in France to better understand the natural history of the disease and identify modifiers of disease progression.

Patients and Methods: Between November 2022 and October 2023, we collected retrospective data from MEN2 patients followed at four tertiary centres in France.

Results: We established a cohort of 748 patients from 335 families. The RET variant was available for 734 patients (98%), mainly located on exons 10 (n = 142, 19%), 11 (n = 278, 38%), and 14 (n = 163, 22%). The mean age at molecular diagnosis was 45. 4 years for index cases and 26. 8 years for relatives. A total of 393 of 467 patients (84%) had undergone surgery for MTC, with 283 localized diseases (pTxN0) at diagnosis, 96 locally advanced (pTxN1), and 7 metastatic (pTxNxM1). After a median follow-up of 12 years, 199 of 304 patients were in remission (65%), 87 had residual disease (29%), and 18 had died (6%). A total of 30% (137/449) of patients benefited from pheochromocytoma surgery, including 91 patients with bilateral adrenal involvement (66%).

Conclusion: This study confirms the feasibility of national epidemiological and genetic data collection. This future database will help identify modifiers of disease progression to better understand phenotypic variability and to tailor the management of MEN2 patients.

Conflict of interest: None

Fundings: This work was funded by the French Society of Endocrinology.

¹ Waguespack et al. Nat Rev Endocrinol. 2011 ² Lodish M, Front Horm Res. 2013 ³ Wells SA et al. Thyroid. 2015