Combining Procalcitonin and Calcitonin for the Diagnosis of Medullary Thyroid Cancer: A Two-Step Approach

Calcitonin (CT) represents the most important biochemical marker of medullary thyroid cancer (MTC), but has certain limits. Procalcitonin (ProCT) has been recognized as an alternative or additional marker for MTC. The aim of the study is to evaluate prospectively the role of ProCT combined with CT in the identification of MTC.

Patients and measurements: 478 patients undergoing thyroidectomy in Padua between January 2023 and June 2024 were enrolled to investigate ProCT levels in comparison with CT for MTC diagnosis. Serum levels of ProCT and CT were dosed preoperatively.

At histological diagnosis, 23/478 (4.8%) patients tested positive for MTC. CT with a cut-off > 10 pg/mL performed as follows: sensitivity 0.91, specificity 0.98, positive predictive value (PPV) 0.7, negative predictive value (NPV) 0.99. CT with a cut-off > 10 pg/mL performed better than ProCT both using the cut-off of 0.04 ng/mL (sensitivity 0.87; specificity 0.96; PPV 0.56; NPV 0.99) and the cut-off of 0.07 ng/mL (sensitivity 0.78; specificity 0.98; PPV 0.72; NPV 0.99). Within the sample of patients with a CT value between 10 and 100 pg/mL, 17/21 (80.9%) patients would have been correctly identified as MTC or non-MTC based on a positive or negative ProCT using the 0.04 ng/mL cut-off.

CT is more sensitive than ProCT as a diagnostic marker for MTC. However, a two-step approach using ProCT as a supplementary marker can help to refine the diagnosis avoiding overtreatment, particularly when CT serum levels lie between 10 and 100 pg/mL.