Serum Binding of Triiodothyronine: Theoretical and Practical Implications for in Vitro Triiodothyronine Uptake*

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Abstract
T3 resin uptake (T3U) is believed to be related to the serum free T4 (FT4) and free T3 (FT3) fraction in the form of the clinical FT4 index and the FT3 index. Although theoretical distribution of T4 and T3 among the different binding proteins has been well studied, the exact relationship between T3U and the FT4 and FT3 fraction has not been demonstrated. We have derived a set of mathematical equations similar to those of Robbins and Rail, showing the dependence of T3U and the FT4 and FT3 fraction on the total T4-binding proteins (TBP) concentrations and on the total T4 concentration. Experimentally determined FT4 and FT3 fractions are used to demonstrate these theoretical relations. The Sephadex competitive binding technique of Sutherland is first used to determine the serum TBP concentrations and their association constants for T4. When parallel titrations are carried out using radioactively labeled T3, the method can be used to study binding of T3 by serum proteins. The distribution of T3 and the association constants for T3 are derived. The association constants of the TBP for T4 are determined to be kTBG = 7.47 × 109 M-1,kTBPA = 1.26 × 108 M-1 where TBG is T4- binding globulin and TBPA is T4-binding prealbumin. The association constants of the TBP for T3 are determined to be k′TBG = 7.79 × 108 M-1 k′TBPA = 6.7 × 106 M-1 and k′Alb = 0.209 × kAlb, where Alb is albumin. Using these values, the serum bound to free ratio (B/F) of T4 or T3 can be calculated from the Sephadex binding study as the sum of the weighted excess capacity of each of the TBP. The distribution of bound hormone among the TBP can be estimated as the weighted excess capacity of the TBP divided by the serum B/F. For 16 serum samples, the serum B/F for T3 is found to correlate linearly with the inverse of T3U, in accordance with the theory presented. However, the B/F ratio for T4 is found to correlate poorly with the inverse of T3U, explaining the lack of correlation between FT4 index and FT4 observed in many clinical conditions