Interactions of Thyroxine with Thyroxine-Binding Globulin of Low Binding Capacity

Abstract

The physico-chemical interactions between thyroxine (T₄) and thyroxine-binding globulin (TBG) of low binding capacity were investigated by radioimmunoassay, equilibrium dialysis, and reverse flow electrophoresis. Knowledge of total and free T₄ (FT₄) concentrations in serum, and of the total binding capacity of the protein carrier (TTBG), allowed the determination of the association constant ruling these interactions (K_tbg). Correlation between T₄ and FT₄ varies with TTBG, shifting the normal range for T₄. The level of FT₄ in serum is a function of the fractional saturation of TBG by endogenous hormones, which depends on T₄ and TTBG. Data on T₄, TTBG, and K_tbg were integrated into the general equation of the law of mass action and the results showed a very significant linear correlation with the values of FT₄ measured by equilibrium dialysis. It is concluded that the misleading results of serum T₄ measurements and of the free T₄ index, obtained in euthyroid individuals with low TTBG, cannot be ascribed to a reduction of the intrinsic sensitivity of the assay due to oversaturation of TBG by endogenous T₄, as previously postulated by others, but to a shift of their normal ranges produced by abnormal variations of TTBG. These results stress the need for data regarding TTBG for the proper interpretation of T₄, and for the calculation of the fractional saturation of TBG and the FT₄ concentration in serum. We have solved this problem by using an empirical equation relating TTBG to T₄ and triiodothyronine (T₃) uptake, which was previously derived by other workers.