calcitonin (Ctn) is a highly specific and sensitive marker for c-cell disease. In the era of precision medicine, preoperative differentiation between c-cell hyperplasia (CCH) and medullary thyroid cancer (MTC) potentially enables a tailored surgical approach, avoiding over- or undertreatment.

379 patients with CCH and intrathyroidal MTC without lymph node or distant metastases underwent primary surgery between 01/2006-10/2023 in two tertiary care centers. All achieved postoperative biochemical cure. Performance of gender-specific, assay-dependent basal and stimulated cut-off calcitonin values as well as stimulated values at 2 and 5 minutes from prospective databases to prognosticate CCH versus MTC was analyzed.

preoperative calcium-stimulated Ctn cut-off value of 812 pg/ml differentiated c-cell disease in men best. Contrary, basal Ctn cut-off of 22 pg/ml in men showed higher PPV compared to the stimulated Ctn cut-off in women. The combination of basal and stimulated Ctn cut-off performed best in discriminating c-cell disease preoperatively: basal Ctn of 27 pg/ml and stimulated 812 pg/ml for men and basal Ctn of 22 pg/ml and stimulated 646 pg/ml for women most accurately prognosticated the type of c-cell disease.

combined gender-specific basal and stimulated Ctn cut-off values remain a useful tool in the diagnostic arsenal to preoperatively discriminate the type of c-cell disease and tailor the appropriate surgical approach individually.