Familial Euthyroid Thyroxine Excess: Characterization of Abnormal Intermediate Affinity Thyroxine Binding to Albumin*

The abnormal high capacity T4 binding site of familial euthyroid T4 excess was separable from prealbumin and T4-binding globulin but not from albumin. We therefore compared T4 binding by albumin preparations isolated from the sera of normal and affected subjects. By equilibrium dialysis, albumin from affected subjects showed an extra T4 binding site (Kd ∼ 50 nM) in addition to the T4 binding sites of normal albumin (Kd ∼ 4 μM). Comparison of the estimated capacity of the additional site (200 μM) with the molar concentration of albumin suggested that only about one third of albumin molecules from affected subjects contained the extra binding site. Estimates of affinity and capacity were used to derive combining powers for the diverse classes of serum T4 binding sites. From these estimates, it appears that the presence of the abnormal site accounts for the approximate doubling of normal mean total T4 (from ∼ 100 nM or 7.7 μg/dl to ∼ 200 nM or 15.5 μg/dl), in order to maintain a normal free T4 in the face of...