thyroxinebinding

Thyroxine binding refers to the reversible association of thyroxine (T4) with circulating plasma proteins that transport the hormone in the bloodstream. In humans, the major carrier is thyroxine-binding globulin (TBG). Smaller fractions are bound to transthyretin (thyroxine-binding prealbumin) and to albumin. Free (unbound) T4 is a small fraction of the total and represents the biologically active portion that equilibrates with tissues.

The binding proteins act as a reservoir that protects T4 from rapid metabolism and clearance and helps maintain a steady supply for distribution to organs. The binding interactions are characterized by high affinity but limited capacity (especially for TBG), while albumin provides greater capacity at a lower affinity. Because only free T4 can enter cells and be available for receptor binding, the concentration of free hormone is tightly regulated by the equilibrium between bound and unbound pools.

Clinical implications arise when levels of binding proteins change. Increases in TBG (for example, during pregnancy or estrogen therapy) raise total T4 and T3 without changing the free hormones or TSH, whereas decreases in TBG (such as liver disease or certain illnesses) lower total hormone levels but can leave free T4 and TSH largely normal. Thyroid function testing typically emphasizes free T4 and TSH rather than total T4 to account for variations in binding proteins. Genetic variations in binding proteins can also affect binding affinity and capacity, influencing diagnostic interpretation.