Direct and indirect techniques for free thyroxin compared in patients with nonthyroidal illness. II. Effect of prealbumin, albumin, and thyroxin-binding globulin.

We studied the correlation of thyroxin (T4)-binding proteins with the apparent free T4 (FT4) in 101 patients with nonthyroidal illness (NTI). Most patients (95%) were seriously ill at the time of blood collection. Concentrations of T4-binding prealbumin (transthyretin), albumin, and T4-binding globulin (TBG) often were low in the sera of these patients. Albumin was the most frequently subnormal, TBG the least. FT4 in serum was determined by five methods represented in 16 different assays. With few exceptions, analog (one-step) FT4 RIAs--both the binding-rate-based RIA and the related FT4 indices (calculated from triiodothyronine-macroaggregated albumin uptake and total T4)--and T4/TBG ratios correlated positively and usually highly significantly (P less than 0.01) with concentrations of prealbumin, albumin, and TBG. Equilibrium dialysis values for FT4 did not correlate with prealbumin concentrations but showed a weakly (P less than 0.03) positive association with albumin and a highly significant (P less than 0.002) positive correlation with TBG. Of the three two-step FT4 RIAs tested, the only statistically significant but weakly (P less than 0.02) positive correlation with T4-binding proteins was between Spiria FT4 and TBG. Thus, in these NTI patients, FT4 estimates vary with methodology and, to a lesser extent, with the particular assay used. The results from two-step FT4 RIAs are least associated with binding protein concentrations.