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* T4 Disposition. In healthy individuals, about 41% of T4 is converted to T3, about 38% is converted to reverse T3 (rT3), and about 21% is metabolized via other pathways, such as conjugation in the liver and excretion in the bile. Reverse T3, which is metabolically inactive, results from removal of the iodine on position 5 of the inner ring. The normal circulating concentration of T4 is 4.5-11 ?g/dL. The normal circulation concentration of T3 is about 100-fold less (60-180 ng/dL).1 Reference 1. Hardman JG, Limbird LE, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. New York, NY: McGraw Hill; 1996:1388. * Carriers for Circulating Thyroid Hormones. Thyroid hormones are transported in the blood by carrier plasma proteins,1 which bind more than 99% of serum T4 and T3.2 Together, the carrier proteins keep the concentration of thyroid hormone constant over a wide range and provide a means for equal distribution of hormone among the tissues.2 Thyroxine-binding globulin (TBG) is the major carrier of thyroid hormones in the circulation because of its extremely high binding affinity, even though it represents only a small fraction of the total serum proteins.2 TBG binds 75% of T4,2 and has 10-20 times greater affinity for T4 than T3.2-4 Transthyretin (TTR) binds T4, but does not significantly bind T3.4 In spite of its low binding affinity, albumin carries about 7% of T4 because of its high serum concentration.2 The thyroid hormones also bind to plasma lipoproteins, with high-density lipoproteins (HDL) being the major binders.3 HDL transports about 3% of T4 and about 6% of T3 in serum.3 The transport proteins are affected by physiological changes, pharmacologic agents, and disease.3 References 1. Hardman JG, Limbird LE, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. New York, NY: McGraw Hill; 1996:1388-1389. 2. Janssen OE, et al. J Clin Endocrinol Metab. 2002;87:1217-1222. 3. Braverman LE, Utiger RD, eds. Werner
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