Reverse T3 is the third-most common iodothyronine the thyroid gland releases into the bloodstream, at 0.9%; tetraiodothyronine (levothyroxine, T4) constitutes 90% and T3 is 9%.

However, 95% of rT3 in human blood is made elsewhere in the body, as enzymes remove a particular iodine atom from T4.

These enzymes operate under complex direction of systems including neurotransmitters, hormones, markers of metabolism and immunological signals.

The levels of rT3 increase in conditions such as euthyroid sick syndrome because its clearance decreases while its production stays the same.

[2] In addition, increased rT3 concentrations result from upregulated thyroxine 5-deiodinase activity in critical illness, starvation and fetal life.