Endocrine Abstracts

Introduction: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor derived from the calcitonin-producing parafollicular C-cells. Calcitonin is the most important tumor marker for MTC both in the diagnostic and follow-up phase. The 2015 ATA guidelines recommend performing additional imaging preoperatively when calcitonin exceeds 500 pg/mL to detect distant metastases. However, this recommendation is based on a single study. Whether this is the optimal cutoff, including other diagnostic parameters, has not been evaluated in other studies. Therefore, the aim of the current study was to investigate the association of preoperative calcitonin and the presence of distant metastases at first clinical evaluation in MTC patients and to find the optimal cut-off.

Methods: We retrospectively collected a cohort of patients treated for MTC in a tertiary care hospital between 1984 and 2023. We included all patients with a preoperative serum calcitonin measurement. The presence of distant metastases was detected by preoperative imaging or biopsy. Performance of calcitonin was visualized by receiver operating characteristic (ROC) curve and analysis of area under the curve (AUC). Diagnostic performance parameters, sensitivity, specificity, positive predicted value (PPV) and negative predicted value (NPV), were calculated for different calcitonin cut-offs.

Results: In total, 123 patients with MTC were included of which 85 were suitable for analysis. Mean age was 55 (± 14.4) years, 46% was female (n = 39) and 71% had sporadic MTC (n = 60). Distant metastases at presentation were found in 34% (n = 29) of all patients. They had significantly higher preoperative calcitonin measurements than those without distant metastases (6036 pg/mL, 25-75 range 1367 – 15148.0 vs 695.0 pg/mL, 25-75 range 112.3 – 1835.0, P < 0.001). The AUC for preoperative calcitonin was 0.8 (CI 95% (0.7 – 0.9), P < 0.001). We calculated diagnostic performance parameters for different cut-offs with 350 pg/mL showing the best results (sensitivity: 97%, specificity: 48%, PPV: 49%, NPV: 96%).

Conclusion: To our knowledge, this is the first study investigating the optimal cut-off and its diagnostic accuracy for preoperative calcitonin in detecting distant metastases at first clinical evaluation in MTC patients. In our study, the best diagnostic performance for calcitonin was at a cut-off of 350 pg/mL, suggesting that the currently recommended cut-off of 500 pg/mL could be interpreted as guidance rather than a fixed cut-off. Ongoing analyses aim to further validate our proposed cut-off taking into account the optimal balance between detecting all distant metastases while minimizing unnecessary imaging.