Altered release of thyroid hormone from the gland
	Iodide in high dosage acutely decreases the release of thyroid hormone from the gland, apparently by inhibition of proteolysis, with a more marked effect in thyrotoxicosis than in the normal gland. Glucocorticoids exert a similar effect that was initially attributed to TSH suppression, but the effect also occurs when TSH is suppressed, as in Graves' disease. Lithium chronically inhibits thyroid hormone release as a result of an apparent decrease in proteolysis of thyroglobulin (Lazarus, 1996). These agents are occasionally used as additional medications in the management of complicated thyrotoxicosis. Table 1: Principal medications that influence thyroid hormone or TSH levels + increase - decrease Modify pituitary TSH secretion Dopamine, dobutamine, glucocorticoids, octreotide - Affect thyroid hormone synthesis and release by delivering iodine load Contrast agents, amiodarone, topical preparations +/- Influence thyroid hormone synthesis or release Lithium, glucocorticoids, aminiglutethimide? - Inhibit T4-T3 5' Deiodination Amiodarone, glucocorticoids, beta blockers* Contrast agents, e.g. iopanoic acid, ipodate - Modify immune function Interleukin 1, interferon α, interferon β Monoclonal antibody therapy see text see text Modify binding of T4 and T3 to plasma proteins a. Alter concentration of T4 binding globulin Estrogen, heroin, methadone Clofibrate, 5-fluouracil, perphenazine, tamoxifen b. Displace T4 and T3 from binding proteins Furosemide, salicylates, phenytoin, carbamazepine Non-steroidal antiinflammatory agents # Heparin Y + + - - - Displace T4 from tissue pool Alkylating agents, oral cholecystographic agents + Modify thyroid hormone action Amiodarone, phenytoin? +/- Increase clearance of T4,T3 Barbiturates, phenytoin, carbamazepine Rifampicin Sertraline?, fluoxetine?, dothiepin? + + + Impair absorption of ingested T4 Aluminium hydroxide, ferrous sulfate, cholestyramine Colestipol, sucralfate, soya preparations Kayexalate - - + : Stimulatory; - : inhibitory; +/- effect depends on thyroid status * Those with membrane-stabilizing effect, e.g. propranolol Y In vitro effect of in vivo heparin administration (see figure) # Some members of the group (see Lim et al, 1988) Table 2: Medications with multiple effects on the pituitary-thyroid axis Glucocorticoids Inhibit TSH secretion Impair thyroid hormone release from the gland Inhibit 5' deiodination of T4 and rT3 Decrease concentration of TBG Amiodarone Delivers iodine load     Iodine-induced thyrotoxicosis (Jod-Basedow)     Iodine-induced hypothyroidism Causes unique form of thyrotoxicosis due to thyroiditis Retards T4 clearance Inhibits 5' deiodination of T4 and rT3 Thyroid hormone receptor antagonist? Augments TSH secretion Phenytoin Inhibits T4 and T3 binding to TBG Accelerates T4 clearance and metabolism Thyroid hormone receptor action ?