The Main Routes of Metabolism of Thyroid Hormones Are Through Deiodination or the Formation of Glucuronides and Sulfates via Hepatic Mechanisms
The main form of metabolism of thyroid hormones involves the removal of iodide molecules. Except for the T3 formed from T4, none of the deiodinated thyronine derivatives has any significant metabolic activity.
The two enzymes involved in T3 and reverse T3 synthesis, 5,-deiodinase and 5-deiodinase, are also involved in the catabolism of thyroid hormones. Only these two enzymes are needed for catabolism because they do not differentiate between the 3 and 5 positions of the phenolic rings of the thyronines. Skeletal muscle, liver, and kidney tissues are important tissues involved in the catabolism of thyroid hormones through deiodination. The formation of thyroid hormone conjugates represents another form of inactivation; sulfates and glucuronides are formed mainly in the liver and kidneys. Conjugation is less common than deiodination as a means of metabolism of thyroid hormones. Another form of metabolism involves modification of the alanine moiety of the thyronines by either transamination or decarboxylation. The deiodinated and conjugated forms of the thyronines are eliminated primarily in the urine; unmetabolized thyronines are excreted with feces through bile secretion. Degradation of the conjugate forms in the feces results in the production of iodide molecules, which are reabsorbed as part of the enterohepatic cycle. Humans are more efficient than dogs in recovery of iodide both intrathyroidally and enterohepatically.One of the striking aspects of thyroid hormones is their long half-lives in humans; T3 has a half-life of 1 day and T4 of 6 to 7 days, whereas most other hormones have half-lives of seconds or minutes. One reason for these long half-lives is the large percentage of the circulating thyronines that are bound to the plasma proteins, which protects them from degradation. The difference in half-lives between T3 and T4 results from the tighter T4 protein binding compared with T3 and the resultant reduction in free circulating hormone. In contrast, the half-life for T4 is relatively short in certain domestic species; dogs and cats exhibit a T4 half-life of less than 24 hours.