Abstract
Background: Performance of thyroid function assays can vary significantly. To address this issue, the Centers for Disease Control and Prevention (CDC) Clinical Standardization Programs conducted an interlaboratory comparison of free thyroxine (fT4) immunoassays (IAs) and laboratory-developed tests (LDTs). This assessment aimed to determine the current performance characteristics of these assays as a first step toward measurement standardization. Thyrotropin (TSH) IAs were also evaluated. Methods: Assays measured 41 blinded individual-donor sera, including a sample from a pregnant woman (for fT4 analysis only) and three serum pools, with 11.3-32.1 pmol/L (0.881-2.49 ng/dL) fT4 and 0.337-21.6 mIU/L TSH in duplicate over 2 days. Passing-Bablok regression analysis performed pre-recalibration compared assays performance to the CDC fT4 reference measurement procedure (RMP) or TSH all-lab mean (ALM). Additionally, the impact of linear regression-based recalibration of assays to the CDC fT4 RMP or TSH ALM was estimated. Inter-assay agreement of sample classification according to the assay-specific reference interval (RI) was assessed pre- and post-recalibration. Results: A total of 21 fT4 and 17 TSH assays participated. Pre-recalibration, median biases of TSH measurements to the ALM were -1.2% [confidence interval or CI -1.8% to -0.4%], and good classification agreement among TSH assays was observed. fT4 assays all showed a negative median bias to the RMP, with higher bias among IAs (median: -20.3%, CI [-21.5% to -19.4%]) than LDTs (median: -4.5%, [CI -6.1% to -3.2%]). Of the individual-donor sera, only 21 out of 40 samples were classified uniformly by all fT4 assays, indicating poor inter-assay agreement. Post-recalibration, agreement improved to 33 out of 40 individual-donor sera correctly classified by all tested IAs and LDTs. Similar improvement in post-recalibration median percent bias was observed for fT4 IAs (median: -0.2, [CI -1.2% to 0.6%]) and LDTs (median: -0.3%, [CI -2.5% to 1.4%]). Conclusions: The comparison among fT4 assays emphasizes the need for measurement standardization to improve accuracy and comparability. This and previous studies demonstrate the possibility to develop common fT4 RIs via standardization, enabling the use of evidence-based clinical guidelines universally in patient care. Recalibration can effectively address high variability in fT4 assays, ensuring consistent diagnostic classification.