Harmonization of free thyroid hormone tests: a mission impossible?

The aim of in vitro testing of thyroid function is to accurately reflect the in vivo activity of key analytes, such as thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4). For these key laboratory parameters, it is highly desirable that assay results are interpretable in relation to consensus reference intervals, which should not vary depending on the choice of method used for measurement. The IFCC Working Group for Standardization of Thyroid Function Tests has recently published three reports on standardization of thyroid function tests in order to resolve the issues concerning method performance and quality specifications, as well as to meet clinical requirements. The aim of the present article is to discuss the relevant contribution of the IFCC Working Group study towards the standardization of free triiodothyronine (FT3) and free thyroxine (FT4) assays. The most important result obtained by this study is the establishment of a reliable candidate reference procedure and some commutable reference materials. These reference materials, including sera collected from blood donors, were measured by the gold standard method, and by several immunoassay methods and two equilibrium dialysis procedures in order to obtain a recalibration of test results. The recalibration on average eliminated assay-specific biases with respect to reference method values. However, sample-related effects remained among the immunoassay methods tested. Although these findings are clearly important, they should only be considered a start towards harmonization of patients test results. In conclusion, further studies are necessary to answer the question of whether standardization and harmonization of the FT3 and FT4 test is an impossible mission (or not).