Endocrine Abstracts

Medullary thyroid carcinoma (MTC) originates from the parafollicular or C cells of the thyroid gland and represents approximately 10% of all thyroid malignancies. The operational classification of FMTC is four or more family members with MTC without objective evidence of pheochromocytoma (PC) and parathyroid hyperplasia. In multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid cancer (FMTC), the majority of germline mutations are restricted to specific positions in exons 10 and 11 of the RET gene. Germline mutations may very occasionally occur in other exons, including exon 14 of the RET gene. 1n 2000 we reported a large kindred where the V804M mutation and the S836S variant were identified and only the V804M mutation associated with FMTC. That time 80 members of the family were evaluated. In the past 15 years the family has grown to 281 members. In our current study we summarized the follow-up data obtained in patients with RET V804M mutation of this family. Molecular screening of the family in the second generation indicated 6 genetically positive patient from 13 that they have germline V804L mutation and a germline S836S polymorphism in separate alleles in exon 14 of the RET gene. Five of the six positive members were operated for medullary thyroid cancer, one patient with known high level of calcitonin and nodular thyroid refused the surgery. However, based on the 15 years of follow up data the cancer patients and the other mutation carriers, showed no disease progression. None of the other family members with positive genetic test had clinical or biochemical evidence of MTC This current data confirm that the V804M mutation associates with FMTC presenting as a mild phenotype.