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Thyroxine (T4) is one of two major hormones produced by the thyroid gland (the other is called triiodothyronine, or T3). T4 and T3 are regulated by a sensitive feedback system involving the hypothalamus and the pituitary gland. The hypothalamus releases the thyrotropin releasing hormone (TRH), which stimulates the pituitary to release the thyroid stimulating hormone (TSH). This causes the thyroid to release T3 and T4 and these in turn regulate the release of TRH and TSH via a feedback control mechanism. Normally, elevated blood levels of T4 and T3 act to decrease the amount of TSH secreted, thereby reducing the production and release of T4 and T3. Over 99% of T4 is reversibly bound to three plasma proteins in blood: thyroxine binding globulin (TBG) binds close to 70%, thyroxine binding pre-albumin (TBPA) binds 20%, and albumin binds 10%. Approximately 0.03% of T4 is in the free, unbound state in blood at any one time. T4 is a useful marker for the diagnosis of hypothyroidism and hyperthyroidism. The level of T4 decreases in hypothyroidism, myxedema and chronic thyroiditis (Hashimoto’s disease). Increased levels of T4 have been found in hyperthyroidism due to Grave’s disease and Plummer’s disease.