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Thyroid hormone synthesis and secretion is regulated by the hypothalamic-pituitary-thyroid axisThyrotropin-releasing hormoneTRHreleased from the hypothalamus stimulates secretion of thyrotropin-stimulating hormoneTSHfrom the anterior pituitaryTSHin turnis the physiologic stimulus for the synthesis and secretion of thyroid hormonesL-thyroxineT 4and L-triiodothyronineT 3by the thyroid glandCirculating serum T 3 and T 4 levels exert a feedback effect on both TRH and TSH secretionWhen serum T 3 and T 4 levels increaseTRH and TSH secretion decreaseWhen thyroid hormone levels decreaseTRH and TSH secretion increase.

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Circulating thyroid hormones are greater than 99bound to plasma proteinsincluding thyroxine-binding globulinTBGthyroxine-binding prealbuminTBPAand albuminTBAwhose capacities and affinities vary for each hormoneThe higher affinity of both TBG and TBPA for T 4 partially explains the higher serum levelsslower metabolic clearanceand longer half-life of T 4 compared to T 3Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormoneOnly unbound hormone is metabolically activeMany drugs and physiologic conditions affect the binding of thyroid hormones to serum proteinssee PRECAUTIONSDrug Interactions and Drug-Laboratory Test InteractionsThyroid hormones do not readily cross the placental barriersee PRECAUTIONSPregnancy

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