Usefulness of the genetic screening in the diagnosis of medullary thyroid carcinoma

Germ-line mutations in the RET proto-oncogene are associated with multiple endocrine neoplasia type 2A (MEN 2A) and with familial medullary thyroid ca rcinoma (FMTC). Detection of these mutations allows the identification of t he affected kindred members, who will develop medullary thyroid carcinoma ( MTC) in 100% of cases, We studied 24 patients of two kindreds (MEN 2A and FMTC), Basal calcitonin levels and pentagastrin-stimulated calcitonin were measured in all patients . The RET mutations were detected by DNA analysis. The RET mutations were identified in 14 patients. Two of them had been oper ated in the past, 2 refused operation and 4 were living abroad. In the 6 re maining, only one showed a thyroid mass, basal calcitonin was normal in all patients except one, and pentagastrin-stimulated calcitonin was negative i n 2 patients. Total thyroidectomy was performed in ail cases. Histology sho wed C-cell hyperplasia in all patients and MTC in 5 of them. In MEN 2A and FMTC DNA analysis allows the identification of RET mutation c arriers, in which presymptomatic thyroidectomy allows and improvement in su rvival.