During the deiodination of T4 in circulation to T3, under the influence of cortisol, deiodinases may catalyze the inner ring deiodination to produce a component known as "reverse" T3 (RT3), which is biologically inert. As illustrated, the iodine residues are "reversed" between the inner and outer rings at the 5 and 5' positions, compared to T3. High levels of RT3 may indicate that a high degree of T4 is being rendered inactive, and hypothyroid-like symptoms may ensue, including clinically elevated levels of TSH.
RT3 is not routinely measured in clinical laboratories, as non-isotopic automated immunoassays are not currently commercially available. However, if elevated TSH persists in patients who are symptomatic for hypothyroidism, RT3 analysis may provide insight as to the diagnosis and prospective treatment.