Circulation and Transport of thyroid hormones T3/T4
Most of the circulating thyroid hormone is bound to transport proteins (70% bound to thyroxine binding globulin (TBG)). Only a very small fraction is free and biologically active. Unbound T4 (fT4) = 0.03%; Unbound T3 (fT3) = 0.3%
When thyroid hormone is bound, it is not active, so the amount of free T3 compared to free T4 is what is important. Thus, measuring total T4 in the blood can be misleading.
Membrane transport of T3/T4
Since they are lipophilic (“fat-loving”) molecules, T3 and T4 cross the cell membrane easily, and function via a well-studied set of thyroid hormone receptors (receptors in the nucleus of the cell);
Although they can even transverse the cell membrane in a passive manner, at least 10 different active, energy dependent and genetic regulated iodothyronine transporters have been identified in humans. They guarantee that intracellular levels of thyroid hormones are higher than extracellular blood plasma or interstitial fluids (tissue fluids).