Clinical Information

Thyroxine (T4) is an iodine-containing hormone secreted by the thyroid gland. T4 and its associate thyroid hormone T3 are responsible for regulating diverse biochemical processes throughout the body which are essential for normal metabolic and neural activity.

Although T3 has greater biologic potency, T4 is normally present in serum in approximately 50-fold excess of circulating T3 and accounts for more than 90% of circulating protein-bound iodine. T4 is 99.9% bound to serum thyroxine binding proteins (TBP). It is transported bound primarily to thyroxine binding globulin (TBG) and secondarily by thyroxine binding prealbumin (TBPA) and albumin. Less than 0.05% of total circulating T4 is unbound and therefore biologically active.

Clinically, T4 measurements are recognized as an aid in the assessment and diagnosis of thyroid status. Elevated T4 values are characteristically seen in patients with overt hyperthyroidism, while T4 levels are generally depressed in patients with overt hypothyroidism. Normal T4 levels and high T3 values are seen in patients with T3- thyrotoxicosis. T4 levels are altered by physiological or pathological changes in TBP capacity, which has a pronounced effect on thyroid hormone concentrations. Consequently, T4 levels may be elevated with increased TBG, seen in pregnancy, administration of oral contraceptives or estrogen, infectious and chronic hepatitis, biliary cirrhosis or congenital TBG increase. Conversely, when TBG levels are decreased, such as in nephrotic syndrome, androgen therapy, glucocorticoid therapy, major systemic illness, or congenital decrease of TBG, T4 may be reduced.

Drugs that compete for protein binding sites such as phenylbutazone, diphenylhydantoin or salicylates can result in a depressed T4 measurement. Serum T4 levels in neonates and infants are higher than in a normal adult due to increased TBG concentration in neonate serum.