rT3

Reverse triiodothyronine (rT3) is an iodothyronine that is considered an inactive metabolite of thyroid hormone. It is produced mainly in peripheral tissues through inner-ring deiodination of thyroxine (T4) by type 3 deiodinase (DIO3), which converts T4 to rT3 and also inactivates T3 to T2. Circulating rT3 is present at much lower concentrations than T3 and is variably measured in clinical practice.

Biological activity of rT3 is limited. It binds thyroid hormone receptors with far lower affinity than T3 and does not reliably trigger the gene transcription programs associated with active thyroid signaling. Thus, rT3 is generally regarded as a metabolite with minimal direct hormonal activity. Like other iodothyronines, it is cleared from the circulation primarily by the liver and kidneys, with degraded products excreted in the urine.

Clinical relevance is mainly as part of the broader assessment of thyroid status in certain states. In euthyroid sick syndrome (non-thyroidal illness), T3 levels typically fall and rT3 levels may rise, reflecting altered peripheral deiodinase activity during illness. In starvation or severe illness, rT3 can be elevated, whereas in overt hypothyroidism or hyperthyroidism, rT3 does not serve as a reliable standalone diagnostic marker. Because assay methods and interpretation vary, rT3 testing is not routinely recommended for the evaluation of thyroid disease and is more commonly used in research or in ambiguous clinical situations.

Measurement of rT3 is performed by specialized immunoassays or chromatography-based methods, but results must be interpreted in the context of other thyroid tests and the patient’s clinical status.

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