Free T4 Index Results are Non-Specific in Patients with Hypothyroxinemia

Abstract

Hypoproteinemia is well-recognized as a cause of hypothyroxinemia. Both hypoproteinemia and hypothyroxinemias are common among patients hospitalized for nonthyroidal illnesses, yet the role of T4-binding proteins in the hypothyroxinemias of nonthyroidal illness is unclear. T4-binding proteins can be measured indirectly by studies of either T3 binding or T4 binding to serum proteins, or they can be measured directly by protein-specific assays. Discrepancies between T3 binding and T4 binding are common in nonthyroidal illness, but it is unknown which, if either, represents T4-binding protein levels. In this study we measured the three T4-binding proteins by protein assays and compared the levels to the T3 binding activity and the T4 binding activity. We selected 150 hypothyroxinemic patients hospitalized for nonthyroidal illnesses solely on the basis of their serum T4 concentrations. Albumin was measured colormetrically; prealbumin (PA) and TBG were measured by immunoassay. T3 binding was measured by in vitro T3 uptake or by equilibrium dialysis, and T4 binding was measured by equilibrium dialysis. In 134 of the 150 hypothyroxinemic patients one or more of the T4-binding proteins was low. The contribution of these hypoproteinemias to the hypothyroxinemias was assessed by calculating the overall T4-binding protein level of each serum from the concentrations of each of the three individual T4-binding proteins measured by protein-specific assays and comparing this overall T4-binding protein level to the protein-bound T4 concentration (i.e., Total T4). The interrelationships between overall T4-binding protein levels, tracer T3 binding and tracer T4 binding were examined. The biochemical mechanisms of hypothyroxinemia were determined from the free T4 concentration, protein-corrected T4 level, and serum TSH without consideration of free T4 index values. The ability of the free T4 index to identify different types of hypothyroxinemias was then evaluated.