BACKGROUND Hereditary medullary thyroid carcinoma can present as a part of multiple endocrine neoplasia syndrome by rearranged during transfection gene mutation. We evaluated the prevalence of rearranged during transfection gene mutation in patients who have medullary thyroid carcinoma and the correlations of genotype with medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism according to the revised American Thyroid Association risk level.

METHODS A total of 331 patients were diagnosed with medullary thyroid carcinoma, 172 of whom were tested for the rearranged during transfection germline mutation by sequencing of exon 8, 10, 11, and 13-16. These patients were diagnosed during the years 1982-2012 at 2 Korean tertiary hospitals. Patients were analyzed according to the route of diagnosis (screened versus index cases) or the mutational site of rearranged during transfection gene (the American Thyroid Association risk group).

RESULTS Rearranged during transfection mutation was found in 23.8% of patients tested, showing a decreasing trend with time. The most commonly mutated codon was codon 634 (37.1%), followed by codon 918 (14.3%). rearranged during transfection-positive patients were younger than rearranged during transfection-negative patients, although no other clinicopathologic characteristics differed. Screened cases were younger and had smaller tumors than index cases. Among rearranged during transfection-positive patients, pheochromocytoma manifested in 35.1% and hyperparathyroidism in 7.0%. Notably, pheochromocytoma and hyperparathyroidism emerged at any time after the diagnosis of medullary thyroid carcinoma. The American Thyroid Association risk-group analysis demonstrated that medullary thyroid carcinoma patients in the highest risk group were younger, had larger tumors, and higher disease-specific mortality. Similar results for pheochromocytoma were found, according to the American Thyroid Association risk group, although the results were not significant.

CONCLUSIONS Korean patients who have medullary thyroid carcinoma showed a similar distribution of rearranged during transfection gene mutation with those in Western countries. The American Thyroid Association risk classification was shown to be useful for pheochromocytoma, as well as for medullary thyroid carcinoma. Familial screening for rearranged during transfection mutation and lifelong monitoring for associated pheochromocytoma should be emphasized in hereditary medullary thyroid carcinoma.