Multiple endocrine neoplasia 2A syndrome: Surgical management

Background/purpose: Currently, molecular genetic diagnostics allow familial types of medullary thyroid carcinoma to be detected at an asymptomatic stage and surgery thus to be performed at a time when prognosis is good. The current report aims to determine the appropriate age for safe prophylactic thyroidectomy in children with multiple endocrine neoplasia (MEN) 2A and mutations at codon 609 according to genotype-phenotype correlations and will discuss surgical procedures.

Methods: The authors describe the case of a family with hereditary MEN 2A syndrome. A DNA analysis of 7 family members confirmed the diagnosis by a mutation at codon 609 of the RET proto-oncogene.

Results: A phaeochromocytoma developed in 2 family members. Four had medullary thyroid carcinoma. A grandson underwent a prophylactic thyroidectomy at the age of 5 on account of genetic evidence. Despite the negative preoperative and intraoperative findings he already had an invasive medullary thyroid carcinoma.

Conclusions: Few genotype-phenotype correlations have been established for MEN 2A disease. According to the natural history of the disease, families with the genotype RET cys609gly should have a more benign disease than high-risk families (mutations at codon 634, 618). From this report the authors conclude that prophylactic thyroidectomy in "609" families should be performed earlier than actually recommended, favorably at the age of 2 to 4 years. Further multicenter studies are needed to provide more clinical and prognostic data for less frequent (codon 609, 630, 791, and 891) RET genotypes.