Calcitonin as a Clinical Biomarker: Unmet Diagnostic needs and Biosensor-based Solutions

A key biomarker for medullary thyroid cancer (MTC), calcitonin (CTN), is a peptide hormone released by thyroid parafollicular C-cells. It facilitates early identification, prognostic evaluation, and post-treatment recurrence monitoring. In nodular thyroid disease, elevated serum CT levels of 60–100 pg/ml are more suggestive of MTC or C-cell hyperplasia (CCH) than imaging or fine-needle aspiration alone. Nevertheless, there are still unmet diagnostic needs, such as false positives from non-thyroidal conditions, difficulties in pediatric populations, and the rise of calcitonin-negative MTC (CNMTC), in which up to 5–10% of cases have normal CTN levels that confuse detection, requiring the use of alternative markers such as procalcitonin (PCT), or progastrin-releasing peptide (proGRP). Despite their dependability, traditional immunoassays have drawbacks such as costly, time-consuming procedures and matrix interferences in complicated biofluids. By using nanomaterials like graphene, carbon nanotubes, gold nanoparticles, and quantum dots for ultrasensitive, real-time CTN detection at picogram levels, biosensor-based systems provide viable substitutes. By improving specificity by molecular imprinting or antibody immobilization, electrochemical, optical, and piezoelectric biosensors allow point-of-care applications in serum or saliva with little sample preparation. This mini review outlines diagnostic gaps, summarizes the most recent data on CTN's therapeutic efficacy, and investigates biosensor advances as alternative instruments for individualized MTC therapy. With the ultimate goal of reducing MTC mortality by proactive screening, next avenues include wearable sensors for ongoing monitoring and clinical validation to bridge bench-to-bedside translation.