Optimal timing of early thyroidectomy in young patients with MEN2A and its impact on disease outcome

BACKGROUND: RET genetic screening identifies individuals at risk of hereditary medullary thyroid carcinoma. The optimal timing for thyroidectomy in gene carriers is debated. METHODS: Outcomes of MEN2A patients diagnosed at ≤ 20 years were evaluated. RESULTS: Of 104 patients, four were index cases, and 100 (96.2%) diagnosed by genetic screening. The mean age at diagnosis was 11.2 ± 5.6 years, and 65.4% were female. The most common pathogenic variant occurred at codon 634 (70.2%). Excluding index cases, 83 patients underwent thyroidectomy, 15 were under active surveillance, and two awaited surgery. The mean age at surgery was 13.2 ± 5.0 years, and the median preoperative basal serum calcitonin (preCTN) level was 28.0 pg/mL (9.9–60.0). Tumor size ranged 0.1–3.5 cm. After a mean period of 10.9 years, 74 (91.4%) patients achieved an excellent response, while 7 (8.6%) had persistent disease (4 with biochemical and 3 with structural disease). Variables associated with persistent disease included age at diagnosis, age at surgery, preCTN levels, and lymph node or distant metastasis. ROC analysis assessed preCTN level as a predictor of lymph node metastasis and persistent disease; optimal preCTN cutoff values were 28.5 pg/mL (100% sensitivity and 53% specificity) and 71.9 pg/mL (100% sensitivity and 88% specificity). CONCLUSIONS: Most young MEN2A patients who underwent thyroidectomy later than recommended by guidelines were disease-free after long-term follow-up, suggesting the possibility of delaying surgery in selected RET carriers with low serum CTN levels.