Thyroxine, the major secretory product of the thyroid gland, is metabolized in the peripheral tissues by phenolic conjugation, deamination, decarboxylation, and a cascade of monodeiodinations. This brief review focuses on the deiodination reactions, which currently are under intensive investigation. One product, 3,5,3'-triiodothyronine (T3), is the major active form of the thyroid hormone, and about 80% of the T3 produced in the body is derived extrathyroidally. Furthermore, a greater fraction of the T3 found on nuclear receptors in pituitary and brain cells is derived intracellularly, as compared to liver and kidney cells. The latter tissues, on the other hand, appear to be the source of most of the circulating T3. Another deiodinase, acting on the nonphenolic ring of T4, gives rise to the hormonally inactive 3,3',5'-triiodothyronine ("reverse" T3 or rT3). A number of physiological and pathological events perturb the deiodination pathway, leading to a decrease in T3 neogenesis and reciprocal changes in the circulating level of T3 (which decreases) and rT3 (which increases). This so-called "low T3 syndrome" is also produced by a number of pharmacological agents. The biological effects resulting from these changes are incompletely understood, but they are potentially important in the body's adjustment to stress and as a site of action of toxic agents. In addition, they are of obvious importance clinically because of their influence on serum T3 and TSH levels, which are commonly used tests of thyroid function.
