PROPHYLACTIC SURGERY FOR MULTIPLE ENDOCRINE NEOPLASIA TYPE IIA AFTER GENETIC DIAGNOSIS - IS PARATHYROID TRANSPLANTATION INDICATED

Identification of germline mutations in the RET proto-oncogene predisp osing to multiple endocrine neoplasia type IIa (MEN-IIa) has allowed a DNA-based approach to diagnosis and treatment by prophylactic thyroid ectomy in children testing genetically positive. Although total thyroi dectomy is the accepted operation for C cell disease, the necessity of routine total parathyroidectomy and autotransplantation as previously described in these asymptomatic children is questionable, particularl y given the low occurrence of hyperparathyroidism in MEN-IIa (10-20%). Thirty-six children (ages 1 month to 12 years) from four MEN-IIa kind reds at risk for disease underwent genetic testing. Mutational analysi s was done using a highly sensitive PCR-based denaturing gradient gel electrophoresis technique. Parathyroid or serum calcium concentrations were determined preoperatively. Of the 36 children at risk, 18 were f ound to have a MEN-IIa mutation; 11 have undergone prophylactic thyroi dectomy at ages ranging from 2 to 12 years (mean 7.5 years). In each c ase, there was no biochemical evidence of hypercalcemia preoperatively , and all parathyroid glands were identified and mere found to be gros sly normal at exploration. Glands were carefully dissected and left in situ. Postoperatively, 10 of the 11 children maintained normocalcemia , allowing discharge within 24 to 36 hours. Resected thyroid glands co ntained C cell hyperplasia in nine, medullary carcinoma in one, and no rmal histology in one. We conclude that an alternative to routine para thyroidectomy may be desirable for prophylactic treatment of MEN-IIa. In situ parathyroid preservation fan be safely achieved without compro mising the completeness of the thyroid resection. This conservative ap proach obviates the potential morbidity associated with total parathyr oidectomy and autotransplantation.