MEDULLARY-THYROID CARCINOMA IN CHILDREN WITH MULTIPLE ENDOCRINE NEOPLASIA TYPES 2A AND 2B

Recently it has become possible to identify persons who have multiple endocrine neoplasia (MEN) syndrome types 2A and 2B based on the presen ce of missense mutations in the RET protooncogene. Kindred members who have inherited these syndromes can be identified before clinical or b iochemical evidence of medullary thyroid carcinoma (MTC) develops, the malignancy that occurs in all affected patients. It is not known whet her prophylactic removal of the thyroid gland early in childhood, base d on a positive genetic test result, has a better clinical outcome tha n that associated with thyroidectomy after MTC is diagnosed clinically or biochemically. The authors' goal was to determine the long term ou tcome for patients with MEN 2A and 2B who had thyroidectomy for MTC du ring childhood. These results were compared with those of patients who had prophylactic removal of the thyroid gland after the genetic diagn osis of MEN 2A was established. The hospital records of 49 children wi th MEN 2A or 2B were reviewed. Each patient had thyroidectomy for MTC before 16 years of age. The mean age at the time of operation was 10 y ears, and the mean follow-up period for those who had surgery before t he availability of direct DNA genetic testing was 9.8 years. The indic ations for surgery included an elevated basal or stimulated plasma cal citonin revel, a positive genetic test result, a thyroid mass, family history of MTC, or a phenotype diagnostic of MEN 2B. All children for whom the diagnosis of MEN 2A was established by direct genetic testing had thyroidectomy within the last 2 years. Of the 11 patients with ME N 2B who underwent thyroidectomy during childhood, 10 had MTC, and onl y three (27%) remain free of disease after the mean follow-up period o f 11 years. One patient died, and seven are alive with persistent MTC. Among the 24 patients with MEN 2A who had their thyroid glands remove d because of a family history of MTC or because of biochemical evidenc e of the disease, 5 (21%) have persistent or recurrent MTC after the m ean follow-up period of 9.3 years. In four of these, the MTC was confi ned to the thyroid gland at the time of thyroidectomy. Of the 14 child ren who had thyroidectomy based on direct DNA testing, MTC was present in 11. Only four had elevated levels of stimulated plasma calcitonin before surgery. None had lymph node metastasis or surgical complicatio ns. The authors conclude that a significant number of patients with ME N 2A or 2B who undergo thyroidectomy in childhood for MTC have persist ent or recurrent disease long-term. The genetic diagnosis of patients with these syndromes may allow for prophylactic surgery before the dev elopment of biochemical or clinical evidence of MTC. This approach is safe, but longer clinical follow-up will be necessary to confirm that MTC has been cured. Copyright (C) 1996 by W.B. Saunders Company.