EARLY TREATMENT OF HEREDITARY MEDULLARY-THYROID CARCINOMA AFTER ATTRIBUTION OF MULTIPLE ENDOCRINE NEOPLASIA TYPE-2 GENE CARRIER STATUS BY SCREENING FOR RET GENE-MUTATIONS

Background. Germline missense point mutations of the ret proto-oncogen e have been shown as causative in multiple endocrine neoplasia type 2 (MEN 2A and 2B) and in familial medullary thyroid carcinoma (FMTC). Mo st of the mutations are found in exon 10, 11, or 16 of the gene and ar e easily recognized by restriction analysis. Methods. Using restrictio n analysis, we screened 58 subjects from nine kindreds. Results. Famil y members (n = 16) already known to be affected with the disease carri ed the germline mutation. Among the 42 subjects apparently unaffected, 37 were not gene carriers and 5 were gene carriers. Basal and pentaga strin-stimulated serum calcitonin levels were normal in two patients a nd abnormal in three. All patients were treated with total thyroidecto my and central node dissection. In all cases multiple foci of MTC were shown at histologic examination. Conclusions. Our data indicate that genetic screening of MEN2 pedigrees allows the early identification of gene carriers. Because surgery of MTC in the preclinical phase has hi gh probability of curing these patients, we suggest genetic screening soon after birth and total thyroidectomy in gene carriers as early as possible.