Direct and indirect techniques for free thyroxin compared in patients with nonthyroidal illness. III. Analysis of interference variables by stepwise regression.

We applied stepwise regression for multivariate analysis of data for free thyroxin (FT4) in serum and for other laboratory tests of thyroid function in patients with nonthyroidal illness. Using the maximum R2 improvement and backward elimination methods to test five variables [prealbumin, albumin, T4-binding globulin (TBG), free fatty acids (FFA), and FFA/albumin molar ratio], we found that the variables with the greatest predictive power clustered according to the methodology of FT4 measurement. Thus, we best predicted the FT4 results obtained by 16 techniques as follows: FT4 measured by one-step (analog) RIAs, with albumin; FT4 determined by two-step (sequential) RIAs, with FFA or FFA/albumin molar ratio; FT4 estimated by a binding-rate-based RIA or conceptually related FT4 indices [based on triiodothyronine (T3) uptake], with TBG; FT4 measured by equilibrium dialysis, with TBG and FFA/albumin molar ratio; and T4/TBG ratios, with either none or prealbumin and albumin. We could very highly (P less than 0.001) predict total T4 and T3 by considering TBG, and total T3 also by considering prealbumin and albumin, whereas reverse T3 was predictable with prealbumin only (negative relationship). We found comparatively weak associations between thyrotropin (TSH) and albumin or TBG. In clinical practice, abnormalities in key variables should call attention to possible effects of these variables on FT4 and other thyroid-test results and thus to the need for appropriate correction or alternative testing.