Reverse triiodothyronine, also known as rT<sub>3</sub>, is an isomer of triiodothyronine (T<sub>3</sub>).
Reverse T<sub>3</sub> is the third-most common iodothyronine the thyroid gland releases into the bloodstream, at 0.9%; tetraiodothyronine (levothyroxine, T<sub>4</sub>) constitutes 90% and T<sub>3</sub> is 9%. However, 95% of rT<sub>3</sub> in human blood is made elsewhere in the body, as enzymes remove a particular iodine atom from T<sub>4</sub>.
The production of hormone by the thyroid gland is controlled by the hypothalamus and pituitary gland. The physiological activity of thyroid hormone is regulated by a system of enzymes that activate, inactivate or simply discard the prohormone T<sub>4</sub> and in turn functionally modify T<sub>3</sub> and rT<sub>3</sub>. These enzymes operate under complex direction of systems including neurotransmitters, hormones, markers of metabolism and immunological signals.
The levels of rT<sub>3</sub> increase in conditions such as euthyroid sick syndrome because its clearance decreases while its production stays the same. The decreased clearance is possibly from lower thyroxine 5-deiodinase activity in the peripheral tissue or decreased liver uptake of rT<sub>3</sub>. In addition, increased rT<sub>3</sub> concentrations result from upregulated thyroxine 5-deiodinase activity in critical illness, starvation and fetal life.