Objective: To evaluate the impact of genetic testing in the management of familial multiple endocrine neoplasia 2A patients.
Design: Retrospective study.
Setting: University teaching hospital, Hong Kong.
Patients: Twenty-two patients from eight multiple endocrine neoplasia 2A families underwent prophylactic total thyroidectomy based on a positive RET mutation genetic testing. All mutations were located at codon 634 of exon 11. Nineteen patients had preoperative basal serum calcitonin measured, and the 12 with normal levels had pentagastrin stimulation tests. Preoperative thyroid ultrasound examination was performed for 17 patients.
Results: There were 13 females and 9 males with a median age of 25.1 (range, 6.1-71.9) years. Histopathology revealed medullary thyroid carcinoma in 17 (77%), C-cell hyperplasia in four (18%), and normal pathology in one (5%) of the patients. Five patients with either C-cell hyperplasia or normal pathology were among the youngest (age range, 6-9 years). The youngest patient with medullary thyroid carcinoma was nearly 9 years old. The median size of medullary thyroid carcinomas was 8.3 (range, 0.1-18) mm, but there were no lymph node metastases. Of 15 patients with normal basal calcitonin levels, 10 had medullary thyroid carcinoma, though two tested negative with the pentagastrin-stimulated calcitonin assay. Five of six patients with normal preoperative ultrasonographic examinations had medullary thyroid carcinoma. Three (14%) of the patients were prescribed long-term calcium and vitamin D supplementation. After a median follow-up of 49 (range, 13-128) months, no patient had recurrence of medullary thyroid carcinoma.
Conclusions: Genetic testing has replaced conventional biochemical and radiological modalities to identifying multiple endocrine neoplasia 2A carriers, in order to offer them prophylactic thyroidectomy. Chinese multiple endocrine neoplasia 2A patients with codon 634 mutation seem to have less aggressive forms of medullary thyroid carcinoma, for whom prophylactic thyroidectomy can be considered at the age of 8 years.