Presymptomatic detection and treatment of Japanese carriers of the multiple endocrine neoplasia type 2A gene.

DNA extracted from the peripheral blood leukocytes of 36 members of five families with multiple endocrine neoplasia (MEN) type 2A was analyzed for mutations of exons 10, 11, 13, 14, and 16 of the RET proto-oncogene by nonisotopic polymerase chain reaction-single-strand conformation polymorphism analysis and automated DNA sequencing. Germline mutations were found in all 9 of the affected individuals and in 6 of the 27 individuals of unknown status. A 70-year-old man who had been completely asymptomatic before genetic diagnosis underwent left adrenalectomy and total thyroidectomy, and was found to have pheochromocytoma and multifocal micromedullary thyroid carcinoma (MTC). A 32-year-old man and a 15-year-old boy, with elevated calcitonin levels detected by the C-cell-stimulation test, but no evident thyroid tumor, underwent total thyroidectomy. Histopathological diagnosis revealed multiple micro MTCs. A 7-year-old girl without evidence of a thyroid tumor or an elevated calcitonin level is being followed up. The remaining two subjects with an evident thyroid tumor and elevated calcitonin levels refused surgery. These results suggest that genetic screening for MEN type 2 afflicted family members can facilitate the presymptomatic detection of gene carriers. Thus, we must carefully evaluate whether immediate prophylactic total thyroidectomy is indicated for gene carriers of MEN 2A without an evident thyroid tumor or elevated calcitonin levels.