A Progress Report of the IFCC Committee for Standardization of Thyroid Function Tests

The IFCC Committee for Standardization of Thyroid Function Tests aims at equivalence of laboratory test results for free thyroxine (FT4) and thyrotropin (TSH).

This report describes the phase III method comparison study with clinical samples representing a broad spectrum of thyroid disease. The objective was to expand the feasibility work and explore the impact of standardization/harmonization in the clinically relevant concentration range.

Two sets of serum samples (74 for FT4, 94 for TSH) were obtained in a clinical setting. Eight manufacturers participated in the study (with 13 FT4 and 14 TSH assays). Targets for FT4 were set by the international conventional reference measurement procedure of the IFCC; those for TSH were based on the all-procedure trimmed mean. The manufacturers recalibrated their assays against these targets.

All FT4 assays were negatively biased in the mid- to high concentration range, with a maximum interassay discrepancy of approximately 30%. However, in the low range, the maximum deviation was approximately 90%. For TSH, interassay comparability was reasonable in the mid-concentration range, but worse in the pathophysiological ranges. Recalibration was able to eliminate the interassay differences, so that the remaining dispersion of the data was nearly entirely due to within-assay random error components. The impact of recalibration on the numerical results was particularly high for FT4.

Standardization and harmonization of FT4 and TSH measurements is feasible from a technical point of view. Because of the impact on the numerical values, the implementation needs careful preparation with the stakeholders.