Over 99% of Triiodothyronine (T4) circulates in blood is bound to carrier proteins; thyroxine-binding globulin (TBG). However, only the free (unbound) portion of T4 is responsible for the biological action. Further, the concentrations of the carrier proteins are altered in many clinical conditions, such as pregnancy. In normal thyroid function as the concentrations of the carrier proteins alters, the total T4 level changes so that the free T4 concentration remains constant. Thus, measurements of free T4 concentrations correlate more reliably with clinical status than total T4 levels. The increase in total T4 levels associated with pregnancy, oral contraceptives and estrogen therapy result in higher total T4 levels while the free T4 concentration remains basically unchanged.
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