Percentile transformation and recalibration functions allow harmonization of thyroid-stimulating hormone (TSH) immunoassay results

Background The comparability of thyroid-stimulating hormone (TSH) results cannot be easily obtained using SI-traceable reference measurement procedures (RPMs) or reference materials, whilst harmonization is more feasible. The aim of this study was to identify and validate a new approach for the harmonization of TSH results. Methods Percentile normalization was applied to 125,419 TSH results, obtained from seven laboratories using three immunoassays (Access 3rd IS Thyrotropin, Beckman Coulter Diagnostics; Architect System, Abbott Diagnostics and Elecsys, Roche Diagnostics). Recalibration equations (RCAL) were derived by robust regressions using bootstrapped distribution. Two datasets, the first of 119 EQAs, the second of 610, 638 and 639 results from Access, Architect and Elecsys TSH results, respectively, were used to validate RCAL. A dataset of 142,821 TSH values was used to derive reference intervals (RIs) after applying RCAL. Results Access, Abbott and Elecsys TSH distributions were significantly different (p < 0.001). RCAL intercepts and slopes were -0.003 and 0.984 for Access, 0.032 and 1.041 for Architect, -0.031 and 1.003 for Elecsys, respectively. Validation using EQAs showed that before and after RCAL, the coefficients of variation (CVs) or among-assay results decreased from 10.72% to 8.16%. The second validation dataset was used to test RCALs. The median of between-assay differences ranged from -0.0053 to 0.1955 mIU/L of TSH. Elecsys recalibrated to Access (and vice-versa) showed non-significant difference. TSH RI after RCAL resulted in 0.37-5.11 mIU/L overall, 0.49-4.96 mIU/L for females and 0.40-4.92 mIU/L for males. A significant difference across age classes was identified. Conclusions Percentile normalization and robust regression are valuable tools for deriving RCALs and harmonizing TSH values.