The Role of Thyroxine Binding in the Establishment of Thyroid Status

Abstract

This paper reviews previously published evidence concerning the view of thyroxine metabolism which holds that thyroxine exchanges rapidly and freely throughout its distribution space. This view is essential for the well known concept of ‘free thyroxine’, that small fraction of the plasma hormone not bound to protein but in equilibrium with the specific binding proteins. ‘Free thyroxine’ is held to be the biologically active fraction of the plasma hormone. A considerable body of evidence inconsistent with the ‘free thyroxine’ hypothesis is examined and details of experiments indicating the essentially permanent nature of thyroxine binding are reviewed. It is concluded that the ‘free thyroxine’ concept as currently defined, is no longer acceptable. A new model of thyroxine metabolism is presented.