Development and application of a novel sensitive immunometric assay for calcitonin in a large cohort of patients with medullary and differentiated thyroid cancer, thyroid nodules, and autoimmune thyroid diseases.

BACKGROUND: Serum calcitonin (sCT) is a useful biomarker for medullary thyroid cancer (MTC). Consensus has not been reached concerning sCT measurements in the evaluation of nodular thyroid disease (NTD).

OBJECTIVE AND METHODS: We developed a new immunofluorometric assay for sCT and have validated it in samples from 794 patients [203 with MTC, 205 with autoimmune thyroid disease (ATD), 248 with NTD, 80 with differentiated thyroid cancer (DTC) 'free of disease', 58 with chronic renal failure (CRF)] and 178 normal individuals, including samples after pentagastrin tests and samples from the washout of 92 FNA procedures in patients with NTD or MTC. We also compared some samples from patients with low or high calcitonin levels using both this assay and the Nichols Institute Diagnostics (NID) assay.

RESULTS: The assay's analytical sensitivity was 1.0 pg/ml. Considering MTC patients prior to surgery, the cut-off values for the 95% reference range were 11.1 pg/ml for males and 5.5 pg/ml for females and employing the ROC curve were 18.4 pg/ml for males and 7.8 pg/ml for females. sCT in patients with MTC was strongly correlated with disease status. Patients with NTD and ATD did not present false-positive results. sCT measurements were significantly correlated with age (excluding MTC and CRF). The NID test had a strong correlation with our assay. A hook effect was observed only with concentrations >200,000 pg/ml.

CONCLUSIONS: We developed a novel sCT assay and validated it in healthy subjects, as well as in a large cohort of patients with MTC, NTD, ATD, DTC, and CRF.