What is the Origin of Reverse T3 (rt3)?

The term is a biochemical descriptor, indicating that the molecular structure of this T3 isomer has its iodine atoms in the "reverse" positions compared to the active T3. Its discovery was crucial in elucidating the complex peripheral metabolism of thyroid hormones beyond simple T4-to-T3 conversion. Clinically, the measurement of rT3 became important in the diagnosis of non-thyroidal illness syndrome, previously known as euthyroid sick syndrome.

What is the Mechanism of Reverse T3 (rt3)?

The primary mechanism governing rT3 production involves the enzyme type 3 deiodinase (D3), which is upregulated in conditions of stress, inflammation, or critical illness. D3 specifically catalyzes the inner ring deiodination of T4, rapidly converting it into inactive rT3 and preventing the formation of active T3. This metabolic shunting serves as a protective mechanism, reducing tissue oxygen consumption and metabolic demand during periods of physiological duress. The ratio of T3 to rT3 is often a more accurate reflection of peripheral thyroid hormone action than TSH or T4 levels alone.

Reverse T3 (rt3)

Meaning

Reverse T3 (rT3) is an inactive, biologically inert metabolite of the primary thyroid hormone thyroxine (T4), formed by the peripheral deiodination of T4 at the inner ring. Unlike the active triiodothyronine (T3), which is formed by outer ring deiodination, rT3 cannot bind effectively to the thyroid hormone receptor and therefore exerts no significant metabolic activity. Elevated levels of rT3 often reflect a physiological adaptation or a state of systemic stress, chronic illness, or caloric restriction, where the body attempts to conserve energy by downregulating metabolic rate.

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