Simulation of the Thyroid Hormone-Binding Protein Interactions in Human Plasma1

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Abstract
A mathematical model based on a set of differential equations representing the reactions of thyroxine (T4) and triiodothyronine (T3) with the binding proteins of human plasma is presented. Simulation of experiments on the kinetics of these reactions established that they are probably vexy rapid at body temperature. The value for the association constant of T4 with albumin was held constant and the effects of changes in the constants for T4 binding by thyroxine-binding prealbumin and thyroxinebinding globulin on the predicted % free T4 at equilibrium were explored. For plasma of average hormone and binding protein content a wide range of values gave results consistent with either the high % (about 0.042%) observed in experiments with undiluted plasma and unpurified T4 or the low % (about 0.028%) found in experiments using diluted plasma or predialyzed labeled T4. In both cases, however, when calculated values were compared with experimental results obtained from plasma of varying binding protein concentrations, satisfactory prediction of the observed % free T4 was obtained only with a very narrow range of values for the association constants. However, the % free T4 in plasmas from patients with various diseases often differed substantially from the values predicted by the model on the basis of the optimum parameter values obtained from the study of plasmas from healthy individuals. Computation of the expected free hormone level for a given plasma may facilitate recognition and investigation of those cases where the observed changes cannot be accounted for by changes in binding protein levels alone.

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