Endocrine Abstracts

JOINT2292

Introduction: Medullary thyroid carcinoma (MTC) is a rare but aggressive endocrine malignancy, often associated with variants in the RET proto-oncogene. RET variants are responsible for multiple endocrine neoplasia (MEN) syndromes (MEN2A, MEN2B). In addition to MTC, these patients may develop other MEN components, including pheochromocytoma and primary hyperparathyroidism. This study aims to evaluate the clinical outcomes of pediatric patients with MEN syndromes who has undergone either prophylactic or therapeutic thyroidectomy; and their long-term surveillance for pheochromocytoma and hyperparathyroidism.

Methods: Retrospective review of medical records of patients (aged <18 years) diagnosed with a pathogenic variant in the RET proto-oncogene between 2000-2024. Collected data included clinical information, biochemical markers, genetic analysis, imaging, and long-term outcomes. Histopathological evaluation classified patients as having benign (benign findings, C-cell hyperplasia) or malignant (micromedullary, multicentric MTC) pathology. Risk stratification was based on RET mutation status according to the 2015 American Thyroid Association (ATA) guidelines for MTC, and recurrence was defined by elevated calcitonin levels and/or radiological evidence of disease.

Results: Twenty-two RET variant carriers were included in the study; 54.5% (n=12) were male. Mean age at presentation was 6.8±0.9 years (95% confidence interval [CI]: 4.8-8.9). According to risk stratification, 22.7% (n=5) were identified as moderate risk, 72.7% (n=16) as high risk, and 4.5% (n=1) as highest risk. All patients underwent total thyroidectomy at a mean age of 8±0.9 years (95% CI: 5.9-10). Histopathological evaluation revealed benign findings in 22.7% (n=5), C-cell hyperplasia in 13.6% (n=3), micromedullary MTC in 50% (n=11), and multicentric MTC in 13.6% (n=3). No statistically significant difference was found between preoperative calcitonin levels and postoperative pathology outcomes in the benign and malignant groups (P=0.111). During postoperative follow-up, 27.3% (n=6) experienced recurrence. A significant association was found between pathology results (benign vs. malignant) and recurrence status (P=0.041), indicating a higher recurrence rate in malignant cases. During the follow-up period (mean: 5&middot;9±0&middot;8 years) no cases of pheochromocytoma or hyperparathyroidism were observed.

Conclusions: Close monitoring of RET variant carriers is essential for early detection and management of MTC. Despite prophylactic thyroidectomy and subsequent diagnosis of MTC, recurrence occurred in some patients, highlighting the necessity of long-term follow-up. Preoperative calcitonin levels did not serve as a reliable predictor of malignancy, thus further research is needed to identify alternative biomarkers. Family screening enables the early identification of at-risk children, allowing prophylactic thyroidectomy to effectively prevent MTC.