Thyroid hormone binding in nonthyroid illness

Abstract

The binding of the thyroid hormones, L-thyroxine (T 4) and L-triiodothyronine (T 3), was examined in eight sera obtained from patients with severe illness and the results compared to those obtained in a concurrently studied normal serum pool. In these eight sera, the values for percent free T 4 (%FT 4) and free T 3 (%FT 3) measured by dialysis were distinctly increased. The calculated values for the absolute concentration of FT 4 in six of the eight sera were increased relative to the value in the normal pool and in all eitht sera were greatly underestimated by a free T 4 index based on an in vitro T 3-uptake test. By contrast, the absolute concentration of free T 3 was distinctly increased in only one of the eight sera and this increase was reflected in the free T 3 index. Mixing of the normal serum pool with seven of the eight sera produced values for %FT 4 that significantly exceeded those in normal pool diluted with buffer so that the resulting values for thyroxine-binding globulin (TBG) binding capacity were equivalent to those in the serum mixtures. By contrast, values for %FT 3 in these sera did not differ in a consistent manner from those in the normal pool diluted with buffer to equivalent values for TBG binding capacity. Ultrafiltrates prepared from each of the eight sera, when employed in place of buffer as diluent for serum in the dialysis method for measuring %FT 4, did not affect the %FT 4 in the normal serum pool. Likewise, immunoglobulin concentrates prepared from three sera were also without effect on the %FT 4 in the normal pool. We conclude that there is present in the serum of some patients with severe nonthyroid illness either a nonultrafilterable binding inhibitor or a protein-protein interaction that interferes with T 4-binding to a greater extent than T 3-binding, thereby resulting in a value for %FT 4 that is greater than can be accounted for by a decrease in TBG. Such a phenomenon might contribute to the underestimation by the in vitro T 3-uptake test of the %FT 4.