Sources of T₃s: Thyroidal Secretion Versus Extrathyroidal Metabolism of T₄

Abstract

In determining the sources of circulating T₃, the description of the pathway for the conversion of T₄ to T₃ (Pitt-Rivers et al. 1955) and its confirmation in man (Braverman et al. 1970; Pittman et al. 1971) as well as in animal species (Schwartz et al. 1971; Fisher et al. 1972) led to the question of the relative significance of extrathyroidal metabolism versus thyroidal secretion. This question was important because its answer reflects on the extent to which T₄ is normally metabolized by conversion to T₃ and the extent to which the metabolic activity of T₄ may depend on its conversion to a metabolically more potent T₃. Subsequently, when the existence of rT₃ in human circulation and thyroglobulin became known, and when it was realized that, as in the case of T₃, the peripheral metabolism of T₄ is also an important source of rT₃, questions were raised about the relative significance of thyroidal secretion versus extrathyroidal metabolism of T₄ as sources of rT₃. Answers to these were important to help understand more fully the relative importance in health (and subsequently in disease) of the pathway of inner ring monodeiodination of T₄ compared with the outer ring monodeiodination to T₃ (Chopra 1974, 1976 a).