Triiodothyronine effects

Defesi, C.R., and Surks, M. I., 1981, 3,5,3 -Triiodothyronine effects on the growth rate and cell cycle of cultured GC cells. Endocrinology, 108 259. 

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... 

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]. 

Thyroxine (3, 5, 3,5-L-teraiodothyronine, T4) is a thyroid hormone, which is transformed in peripheral tissues by the enzyme 5 -monodeiodinase to triiodothyronine. T4 is 3-8 times less active than triiodothyronine. T4 circulates in plasma bound to plasma proteins (T4-binding globulin, T4-binding prealbumin and albumin). It is effective in its free non-protein-bound form, which accounts for less than 1%. Its half-life is about 190 h. 

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 concentration of Li+ in the thyroid is three to four times that in serum [179]. It is thought that Li+ may be concentrated in the thyroid gland by a mechanism similar to the incorporation of iodide, I-, resulting in competition between Li+ and I the levels of intracellular 1 decrease when those of Li+ increase, and vice versa [182]. Li+ inhibits both the ability of the gland to accumulate 1 and the release of iodine from the gland. In vitro, Li+ has no effect on thyroid peroxidase, the enzyme that catalyzes the incorporation of I" into tyrosyl residues leading to thyroidal hormone synthesis, but does increase the activity of iodotyrosine-deio-dinase, which catalyzes the reductive deiodination of iodotyrosyls, thus maintaining the levels of intracellular I [182]. The increase in iodoty-rosine-deiodinase activity is probably a response to the Li+-induced decrease in the concentration of thyroidal I". Li+ has no effect on the conversion of thyroxine to triiodothyronine. The overall effect of this competition between Li+ and 1 is, therefore, reduced levels of thyroid hormone in the presence of Li+. 

Krasner, L.J., Wendling, W.W., Cooper, S.C., Chen, D., Heilmann, S.K., Eldridge, C.J., McClurken, J.B., Jeevanandam, V., and Carlsson, C., Direct effects of triiodothyronine on human internal mammary artery and saphenous veins,. Cardiothorac. Vase. Anesth., 11, 463-466,1997. 

The Class III effects of amiodarone develop over several weeks. This time-course is similar to that seen in thyroid gland ablation [25]. It is well known that patients with hypothyroidism have long QT intervals which are indicative of prolonged action potentials. Amiodarone has been shown to inhibit the conversion of thyroxine (T4) to triiodothyronine (T3) both in human subjects [26] and in vitro [27]. It has been argued that the Class III effects of amiodarone are due to its effects on thyroid hormones [28]. Others, however, argue that there is no relationship between prolongation of ventricular refractory period by amiodarone and thyroid state [29]. 

Triiodothyronine (Cytomel, T3). T3 is also an effective augmenting agent. It is important to use the T3 thyroid hormone instead of thyroxine (T4). T4 is the form most often used to treat hypothyroidism, but T3 crosses from the bloodstream to the brain more easily and thus is better for treating depression. T3 is usually tolerated well and is taken at 25-50 pg/day in split doses. When taking T3, laboratory tests to check thyroid function should be performed periodically. 

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

Triiodothyronine (Cytomel). A reportedly effective augmentation strategy for major depression, thongh two recent studies are negative, a controlled study for OCD, utilizing a daily dose of 25-50 ag, did not find triiodothyronine to be effective. 

Youson JH, Manzon RG, PeckBJ, Holmes JA (1997) Effects of exogenous thyroxine (T4) and triiodothyronine (T3) on spontaneous metamorphosis and serum T4 and T3 levels in immediately premetamorphic sea lampreys, Petromyzon marinus. J Exp Zool 279 145-155... 

Walpita CN, Van der Geyten S, Rurangwa E, Darras VM (2007) The effect of 3,5,3 -triiodothyronine supplementation on zebrafish (Danio rerio) embryonic development and expression of iodothyronine deiodinases and thyroid hormone receptors. Gen Comp Endocrinol 152 206-214... 

The thyroid releases predominantly thyroxine (T4). However, the active form appears to be triiodothyronine (T3) T4 is converted in part to T3, receptor affinity in target organs being 10-fold higher for T3. The effect of T3 develops more rapidly and has a shorter duration than does that of T4. Plasma elimination tip for T4 is about 7 d that for T3, however, is only 1.5 d. Conversion of T4 to T3 releases iodide 150 pg T4 contains 100 pg of iodine. 

Z)-2,3-Methanothyronine 59 and its dibromo derivative 60 have comparable activity with the thyroxine 61, a thyroid hormone [66], which exhibited thyro-mimetic activities in basal metabolism and antigoiter tests (comparison of oxygen consumption and heart rate in normal and thyroidectomized rats) but did not have an inhibitory action on the metabolism developed by triiodothyronine [66]. (Z)-2,3-Methanohistidine 62, tested on rat liver, is an effective inhibitor of histidine decarboxylase, Eq. (23) [67]. 

Bimevicius R, Kazanavicius G, Zalinkevicius R, Prange AJ. Effects of thyroxine as compared with triiodothyronine in patients with hypothyroidism. New Engl J Med 1999 340 424-9. 

Thyroid effect. Goffee oil, administered orally to 11 healthy normolipemic volunteers at a dose of 2 g/day for 3 weeks, produced no effect on serum total and free thyroxine, triiodothyronine, and thyroid-stimulating hormone... 

Mechanism of Action A synthetic form of triiodothyronine (T3), a thyroid hormone involved in normal metabolism, growth, and development. Possesses catabolic and anabolic effects. Therapeutic Effect Increases basal metabolic rate, enhances gluco-neogenesis, and stimulates protein synthesis. 

Mecfianism of Action A thiourea derivative that blocks oxidation of iodine in the thyroid gland and blocks synthesis of thyroxine and triiodothyronine. Therapeutic Effect Inhibits synthesis of thyroid hormone. 

Lithium blocks the release of thyroxine (T4) and triiodothyronine (T3) mediated by thyrotropin (Kleiner et ah, 1999). This results in a decrease in circulating T4 and T3 concentrations and a feedback increase in serum thyrotropin concentration. It also inhibits thyrotropin-stimulated adenylate cyclase activity (Kleiner et ah, 1999). Lithium has varying effects on carbohydrate metabolism. Increased and decreased glucose tolerance and decreased sensitivity to insulin have been observed (Van derVelde Gordon, 1969). In animals, lithium decreases hepatic cholesterol and fatty acid synthesis. 

Arnsten AE, lin GH, Van Dyck CH, et al The effects of S-HTj receptor antagonists on cognitive performance in aged monkeys. Neurobiol Aging 18 21-28, 1997 Aronson R, Offman JH, Joffe RT, et al Triiodothyronine augmentation in the treatment of refractory depression a meta-analysis. Arch Gen Psychiatry 53 842-848, 1996... 

Whitworth P, Kendall DA Effects of lithium on inositol phospholipid hydrolysis and inhibition of dopamine D, receptor-mediated cyclic AMP formation by carbachol in rat brain slices. J Neurochem 53 536-541, 1989 Whybrow PC The therapeutic use of triiodothyronine and high dose thyroxine in psychiatric disorder. Acta Med Austriaca 21 44-47, 1994 Whybrow PC Update on thyroid axis approaches to treatment of rapid cycling bipolar disorder. Paper presented at the annual meeting of the New Clinical Drug Evaluations Unit (NCDEU), Boca Raton, EL, May 30, 1996... 

For example, low levels of thyroxine (T4) have been found in patients with significant confusion and memory problems after ECT. Furthermore, consistent with data from animal studies, 50 pg of triiodothyronine (T3) given before ECT diminished amnestic effects and accelerated the antidepressant effect of ECT (134). 

Excessive catecholamine action is an important aspect of the pathophysiology of hyperthyroidism, especially in relation to the heart (see Chapter 38). The 13 antagonists are beneficial in this condition. The effects presumably relate to blockade of adrenoceptors and perhaps in part to the inhibition of peripheral conversion of thyroxine to triiodothyronine. The latter action may vary from one 13 antagonist to another. Propranolol has been used extensively in patients with thyroid storm (severe hyperthyroidism) it is used cautiously in patients with this condition to control supraventricular tachycardias that often precipitate heart failure. 

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