Thyroxine , metabolism

Dronedarone is a structural analog of amiodarone and lacks iodine atoms. The design was intended to eliminate action of the parent drug on thyroxine metabolism and to modify the half-life of the drug. Dronedarone has multiple actions like amiodarone, blocking IKr, IKs, ICa, INa, and adrenoceptors. The drug has a half-life of 24 hours and was administered twice daily in the initial clinical trials. No thyroid or pulmonary toxicity has been noted during early use. 

Hypothyroidism developed within 2 weeks of rifampicin therapy in these patients and resolved when it was withdrawn. Rifampicin increases thyroxine clearance, possibly by enhancing hepatic thyroxine metabolism and the biliary excretion of iodothyronine conjugates. In healthy volunteers rifampicin reduces circulating thyroid hormone concentrations without affecting thyrotropin, suggesting that rifampicin directly reduces thyroid hormone concentrations. 

Bastomsky CH. 1977. Enhanced thyroxine metabolism and high uptake goiters in rats after a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Endocrinology 101 292-296. 

OH-PCBs can also influence thyroxine metabolism. Some of the OH-PCBs that are retained in blood were shown to strongly inhibit sulfation of thyroxine in vitro [204-206]. As sulfation is a major regulation pathway of thyroxine in the fetus, the OH-PCBs may negatively influence the development of the fetus, and in particular fetal brain development [44]. Diodinase mediation is another pathway for thyroxine metabolism e.g., to the active hormone triiodothyronine. Hydroxylated metabolites of CB-77 were shown to inhibit triiodothyronine formation in an in vitro assay using rat hepatic microsomes [207],... 

The effect of beta-adrenoceptor antagonists on thyroid hormone metabolism is unlikely to play a significant role in their use in hyperthyroidism. Since D-propranolol has similar effects on thyroxine metabolism to those seen with the racemic mixture, membrane-stabilizing activity may be involved (176). 

Phenytoin decreases the urinary excretion of 17-ketosteroids and 17-hydroxycorticosteroids by stimulating the conversion of cortisol to 6-P-hydroxycortisol it also diminishes serum FSH and the sperm count in semen, and thereby reduces fertility, Phenytoin also lowers the serum thyroxine concentration, probably by competitive displacement of thyroxine from its protein-binding sites free thyroxine also tends to be low. Serum triiodothyronine is low, probably as a result of stimulated metabohsm in the liver, but the concentration of TSH is unaffected by the altered thyroxine metabolism. 

Emi, Y., Ikushiro, S., and Kato, Y. (2007) Thyroxine-metabolizing rat uridine diphosphate-glucuronosyltransferase 1A7 is regulated by thyroid hormone receptor. 

Deiodination of Mono- and Diiodotyrosine and Diiodothyronine Thyroxine Metabolism... 

Higgs, D. A., and J. G. Eales. 1971. Iodide and thyroxine metabolism in the brook trout, Salvelinus fontinalis (Mitchill), during sustained exercise. Can. J. Zool. 49(9) 1255-1269. [ I]... 

Thyroxine Metabolism. Thyroxine or triiodothyronine, elaborated by the gland inlte the blood, is bound to a specific protein, a glycoprotein, which is one of the a-glob-ulins (thyroxine-binding globulin, TBG). 

The term chiral recognition refers to a process m which some chiral receptor or reagent interacts selectively with one of the enantiomers of a chiral molecule Very high levels of chiral recognition are common m biological processes (—) Nicotine for exam pie IS much more toxic than (+) nicotine and (+) adrenaline is more active than (—) adrenaline m constricting blood vessels (—) Thyroxine an ammo acid of the thyroid gland that speeds up metabolism is one of the most widely used of all prescription... 

The thyroid gland, located in the base of the neck, exerts i key role on growth and metabolism. In contrast with that of some of the other endocrine glands, this control is effected Ihrough a pair of relatively simple molecules, thyroxine, and its close congener, triiodothyronine. Cases of thyroid deficien-cy (hypothyroidism) are common enough to warrant the production... 

Thyroid gland. An endocrine gland that secretes thyroxin and triiodothyronine, hormones that modulate the rate of cellular metabolism. 

Propylthiouracil (PTU), but not methyl-mercaptoi-midazole (MMI), has an additional peripheral effect. It inhibits the monodeiodination of thyroxine to triiodothyronine by blocking the enzyme 5 mono-deiodinase [1]. In humans the potency of MMI is at least 10 times higher than that of PTU, whereas in rats PTU is more potent than MMI. The higher potency of MMI in humans is probably due to differences in uptake into the thyroid gland and subsequent metabolism, because in vitro inhibition of thyroid peroxidase by MMI is not significantly more potent than by PTU [1, 6]. Whether antithyroid drags have additional immunosuppressive actions is a matter of discussion [1, 2]. 

Triiodothyronine (3, 5,3-L-triiodothyronine, T3) is a thyroid hormone. It is producedby outer ring deiodination of thyroxine (T4) in peripheral tissues. The biologic activity of T3 is 3-8 times higher than that of T4. T3 is 99.7% protein-bound and is effective in its free non-protein-bound form. The half-life of triiodothyronine is about 19 h. The daily tur nover of T3 is 75%. Triiodothyronine acts via nuclear receptor binding with subsequent induction of protein synthesis. Effects of thyroid hormones are apparent in almost all organ systems. They include effects on the basal metabolic rate and the metabolisms of proteins, lipids and carbohydrates. 

The functional form of thyroxine (T3) is generated by the deiodination of T4, and PCBs can influence the tissue levels of this form by disturbing metabolism, as well as by reducing the binding of T4. PCBs have been shown to inhibit the sulfation of thyroid hormones and the deiodination of T4 to T3. They can also induce the glucuronyl transferase that conjugates T4 (Brouwer et al. 1998). 

C03-0144. The thyroid gland produces hormones that help regulate body temperature, metabolic rate, reproduction, the synthesis of red blod cells, and more. Iodine must be present in the diet for these thyroid hormones to be produced. Iodine deficiency leads to sluggishness and weight gain, and can cause severe problems in the development of a fetus. One thyroid hormone is thyroxine, whose chemical formula is... 

Despite the availability of a wide array of thyroid hormone products, it is clear that synthetic levothyroxine (LT4) is the treatment of choice for almost all patients with hypothyroidism. LT4 mimics the normal physiology of the thyroid gland, which secretes mostly T4 as a prohormone. As needed, based on metabolic demands, peripheral tissues convert thyroxine (T4)... 

M24. Mendel, C. M., Laughton, C. W., McMahon, F. A., and Cavalieri, R. R., Inability to detect an inhibitor to thyroxine-serum protein binding in sera from patients with nonthyroidal illness. Metabolism 40, 152-159 (1991). 

MISCELLANEOUS ARYLALKANOIC ACIDS It has been known for some time that thyroxine, and related compounds such as liothyronine (88) are effective in lowering serum cholesterol. The normal metabolic activity of this class of thyroid active compounds has precluded their use as hypocholesterol-emic agents. 

The thyroid hormones are lipophilic and relatively insoluble in the plasma. Therefore, they are transported throughout the circulation bound to plasma proteins such as thyroxine-binding globulin (75%) and albumins (25%). Approximately 99.96% of circulating thyroxine is protein bound. Bound hormone is not available to cause any physiological effects however, it is in equilibrium with the remaining 0.04% that is unbound. This free form of the hormone is able to bind to receptors on target tissues and cause its effects. Thyroid hormone has many metabolic effects in the body ... 

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