<p>Approximately 70% of secreted T<sub>4</sub> is deiodinated to equal amounts of T<sub>3</sub> and reverse triiodothyronine (rT<sub>3</sub>), which is calorigenically inactive. T<sub>4</sub> is slowly eliminated through its major metabolic pathway to T<sub>3</sub> via sequential deiodination, where approximately 80% of circulating T<sub>3</sub> is derived from peripheral T<sub>4</sub>. The liver is the major site of degradation for both T<sub>4</sub> and T<sub>3</sub>, with T<sub>4</sub> deiodination also occurring at a number of additional sites, including the kidney and other tissues.</p><p>Elimination of T<sub>4</sub> and T<sub>3</sub> involves hepatic conjugation to glucuronic and sulfuric acids. The hormones undergo enterohepatic circulation as conjugates are hydrolyzed in the intestine and reabsorbed. Conjugated compounds that reach the colon are hydrolyzed and eliminated as free compounds in the feces. Other minor T<sub>4</sub> metabolites have been identified. <sup class="text-reference-group"><a class="reference-popover-link" data-content="American Association of Clinical Endocrinologists (AACE): Clinical Practice Guidelines for Hypothyroidism in Adults" href="#reference-F4636">15</a></sup></p><p class="d-none d-sm-block"><strong>Hover over products below to view reaction partners</strong></p>