Reverse triiodothyronine

Reverse triiodothyronine (rT3) is a metabolite of the thyroid hormone triiodothyronine (T3). It is formed by the deiodination of T3 in a reaction catalyzed by the enzyme iodothyronine deiodinase. rT3 is considered an inactive metabolite because it does not bind to thyroid hormone receptors and does not have the biological activity of T3.

Structure and Synthesis

Reverse triiodothyronine is structurally similar to T3, but with one of the iodine atoms removed. This deiodination occurs at the outer ring of the T3 molecule, resulting in a molecule with three iodine atoms arranged in a different configuration. The enzyme responsible for this conversion, iodothyronine deiodinase, exists in three forms: type 1, type 2, and type 3. Type 1 and type 2 deiodinases can both produce rT3, but type 3 deiodinase does not.

Function and Regulation

Although rT3 does not bind to thyroid hormone receptors and does not have the biological activity of T3, it plays a role in the regulation of thyroid hormone levels in the body. The production of rT3 increases when the body is under stress, such as during illness or fasting. This is thought to be a protective mechanism that reduces the metabolic rate and conserves energy. The levels of rT3 in the blood can be measured as part of a thyroid function test to assess the overall activity of the thyroid gland.

Clinical Significance

Abnormally high levels of rT3 can occur in conditions such as nonthyroidal illness syndrome (NTIS), also known as euthyroid sick syndrome, and in some cases of hypothyroidism. In NTIS, the increase in rT3 is thought to be a response to severe illness or stress. In hypothyroidism, high levels of rT3 may be due to a deficiency of the enzymes needed to convert T3 to its active form.

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