Accuracy Issues in Free Thyroxine Testing Methods

The incidence of low neonatal free thyroxine (T4) assay results is methodology-dependent. Nonanalog free T4 assay results represent free T4 concentrations when free T4 is the only form of T4. Similar analog-based free T4 assay results are produced by an extraordinary range of free T4 concentrations, when free T4 is the only form of T4. Adding albumin or transthyretin to free T4 concentrations greatly decreased free T4 concentrations, as expected, but increased analog-based free T4 assay results. By contrast, adding thyroxine-binding globulin decreased free T4 concentrations and free T4 assay results; but these free T4 concentrations were not represented by assay results. There was no specificity for the free form of T4 versus bound forms of T4 in some free T4 assay results. The protein that binds T4 can have a major influence on some of the total T4 assay results that may be used in free T4 index methods.