Reverse Triiodothyronine

3,3′,5′-Triiodo-L-thyronine also known as reverse triiodothyronine or reverse T3 (rT3), differs from 3,3′,5-Triiodo-L-thyronine (T3) in the positions of the iodine atoms in the molecule. The majority of circulatory rT3 is synthesized by peripheral deiodination of thyroxine (T4). Both T3 and rT3 bind to thyroid hormone receptors, but in contrast to T3, rT3 has not been found yet to stimulate receptor metabolic activity; it blocks receptor sites from T3 activation. The ratio of rT3 to T3 is a valuable biomarker of the metabolism and function of thyroid hormones because the process of 5’ monodeiodination that converts T4 to T3 and rT3 to 3,3’-T2 is inhibited in a number of non-thyroidal conditions such as fasting, anorexia nervosa, malnutrition, diabetes mellitus, stress, severe trauma or infection, hemorrhagic shock, hepatic dysfunction, pulmonary diseases and others. This scenario is known as “Sick euthyroid” syndrome or “Low T3” syndrome. An elevated ratio of rT3 over T3 is therefore indicative of “sick euthyroid” syndrome and helps to exclude a diagnosis of hypothyroidism, particularly in critically ill patients1–9. The concentration of rT3 could be high in patients on the following medications: amiodarone, dexamethasone, propylthiouracil, ipodate, propranolol, and the anesthetic halothane. The concentration of rT3 could be low in patients on Dilantin, which decreases rT3 due to its displacement from thyroxine-binding globulin and therefore generates an excessive clearance of rT3.