Prophylactic thyroidectomy in MEN 2 carriers: histological findings and outcome in 40 youngsters.

BARONTINI M; SANSÓ G; VIEITES A; ACHA O; MAGLIO S; LEVIN G; IORCANSKY S

Delphi, Grecia

Workshop; 11 International Workshop on Multiple Endocrine Neoplasia; 2008

Background: Multiple endocrine neoplasia type 2 (MEN2) is an inherited disease caused by germline mutations in the RET proto-oncogen. Carriers of RET mutations are at risk for developing medular thyroid carcinoma (MTC) at young age. Detection of mutations of the RET proto-oncogen provides the basis for prophylactic thyroidectomy in children. Aim: In the present study, we report the results of prophylactic thyroidectomy in 40 carriers of RET mutations performed at ages from 17m to 21y (median 10y; males:22 ; females:18). Twenty seven carriers belonged to 15 families with MEN 2A, 11 to 3 families with FMTC and 2 to one family with MEN 2B. Results: Level 2 mutations were harboured by 38 carriers: 36 in exon 11 codon 634, and 2 in exon 11 codon 611. The remaining 2 carriers showed the typical MEN2B features and presented the clasical Met918Thr mutation (level 3). Histology was normal only in a 4-year-old carrier. The other 39 carriers had C-cell hyperplasia and in 30 of them MTC was present. MTC was unilateral in 13 and bilateral in 17. In 6/17 bilateral, multifocal MTC was found and one of them presented regional lymph node metastases. Lymphocitic thyroiditis was detected in 3 specimens. Preoperative basal calcitonin levels were increased in 16/40 children: in 3/9 younger than 5 y., in 3/15 with ages between 5 and 10 y. and in 10/16 of 11 to 21 years of age. In all patients under 10 y. serum calcitonin levels dropped to normal after surgery while they remained high in 3/10 patients older than 10 y. It is worth mentioning that the two MEN2B children who underwent prophylactic thyroidectomy at 7 y. showed normal pre-operative calcitonin levels which remained undetectable during the 3-year-follow up. All patients are still alive. They were followed up between 1 and 25 years. (median 5y) post thyroidectomy. No patient presented any other associated endocrine neoplasia indicating that MTC is the first manifestation of MEN2 in juvenile carriers. Conclusions: The results of this study emphasize the importance of early screening and preventive thyroidectomy in children at risk to develop MTC.