Thyroxine (T4), the principal thyroid hormone largely bound to transport proteins, especially TBG. Given normal levels of thyroid hormone-binding proteins, hyperthyroidism is characterized by increased levels of circulating T4, hypothyroidism by decreased levels. Exceptions to this parallelism between thyroid status and total T4 concentration are found. Levels of TBG are known to be altered under various physiological, pharmacological and genetic conditions. Thus, elevated T4 levels may be obtained when TBG levels are high, as in pregnancy, acute intermittent  porphyria, hyperproteinemia, hereditary TBG elevation and in patients undergoing estrogen therapy or taking oral contraceptives. Total T4 levels may be depressed when TBG levels are low, as in nephrotic, hepatic, gastrointestinal and neoplastic disorders; in acromegaly, hypoproteinemia and hereditary TBG deficiency; and in patients undergoing androgen, testosterone or anabolic steroid therapy.