Effects of Thyroid Hormones

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. 

Ahlgren SC, Wallace H, Bishop J, Neophytou C, Raff MC 1997 Effects of thyroid hormone on embryonic oligodendrocyte precursor cell development in vivo and in vitro. Mol Cell Neurosci 9 420-432... 

During treatment of hyperthyroidism, Lp(a), as well as LDL cholesterol and apolipoprotein B, increases, indicating an effect of thyroid hormone on receptor activity and on protein synthesis. The opposite effect is observed in treatment of hypothyroidism (B27, E9, K16). 

K., Seckl, J.R., (2000) Postnatal handling increases the expression of cAMP inducible transcription factors in the rat hippocampus effects of thyroid hormone and serotonin /. Neurosci 20 3926-3935. 

In the context of an updated comprehensive evaluation of mood stabilizers, it is worthwhile to mention the recent studies showing a beneficial effect of thyroid hormones and melatonin in rapid-cycling patients. A detailed account of these hormones appears elsewhere in this book series and is briefly described by Halbreich in Chapter 17. 

Bartalena L, Bogazzi F, Martino E. Adverse effects of thyroid hormone preparations and antithyroid drugs. Drug Saf 1996 15(l) 53-63. 

Table 1 Summary of studies on the effects of thyroid hormones on bone mineralization...

Data from more than 30 studies of the effect of thyroid hormone on bone have been reviewed (37). The results have supported the view, expressed before (38), that there is a small, but statistically significant, adverse effect on bone mineral density, especially in postmenopausal women. 

Krolner B, Jorgensen JV, Nielsen SP. Spinal bone mineral content in myxoedema and thyrotoxicosis. Effects of thyroid hormone(s) and antithyroid treatment. Clin Endocrinol (Oxf) 1983 18(5) 439 16. 

Stathatos NWL. Effects of thyroid hormone on bone. Clin Rev Bone Mineral Metab 2005 2 135-50. 

The results on the effect of thyroid hormone on myelin lipid synthesis correlate well with the in vivo changes induced under altered thyroid functions, proving, thereby, the direct influence of T on brain maturation. Another in vitro system used to demonstrate such a direct effect of thyroid hormone on myelination was an explant culture of cerebella obtained from newborn rats. 

The clinical manifestations of hyperthyroidism and hypothyroidism are listed in Table 31-2. From a pharmacotherapeutic standpoint, hyperthyroidism is treated with drugs that attenuate the synthesis and effects of thyroid hormones. Hypothyroidism is usually treated by thyroid hormone administration (replacement therapy). The general aspects and more common forms of hyperthyroidism and hypothyroidism are discussed here, along with the drugs used to resolve these primary forms of thyroid dysfunction. 

Lamb JC IV, Harris MW, McKinney JD, et al. 1986. Effects of thyroid hormones on the induction of cleft palate by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57BL/6N mice. Toxicol Appl Pharmacol 84 115-124. 

Sher ES, Xu XM, Adams PM, Craft CM, Stein SA (1998) The effects of thyroid hormone level and action in developing brain Are these targets for the actions of polychlorinated biphenyls and dioxins Toxicol Ind Health, 14 121-158. 

Membrane-containing fractions displaying T3-binding activities have been detected in a variety of cell types [13-16], Rat liver [15] and erythrocyte [16] plasma membranes, for instance, contain T4- and T3-binding sites with affinities ranging from 1 to 10 x 10 10 M for T3. It is not clear whether the function of these sites is related to the transport of thyroid hormones from the blood to the cell or if they represent receptors responsible for non-nuclear effects of thyroid hormones [17,18]. 

Effects of thyroid hormone on the receptor-adenylate cyclase system in the adipocyte and the hepatocyte... 

Recently Exton and co-workers [93] have proposed that adrenergic responsiveness in skeletal muscle is regulated by thyroid hormones at two levels, i.e., 1) stimulation of /3-adrenergic receptors and adenylate cyclase activity and 2) increased activity of phosphoprotein phosphatases. Such results would explain the effect of thyroid hormones on glycogen metabolism in muscle although the primary mechanism of these actions remains unknown. 

The higher leakiness to protons noted in the inner mitochondrial membranes of the rat relative to A. vitticeps has a parallel in the effects of thyroid hormones on respiration. Increased... 

Adverse effects of thyroid hormone parallel the increase in metabolic rate. The symptoms and signs are those of hyperthyroidism. Symptoms of myocardial ischaemia, atrial fibrillation or heart failure are liable to be provoked by too vigorous therapy or in patients having serious ischaemic heart disease who may even be unable to tolerate optimal therapy. Should they occur levothyroxine must be discontinued for at least a week and begim again at lower dosage. Only slight overdose is needed to precipitate atrial fibrillation in patients over 60 years. 

Hoppner, W., and Sieiz, H -J. (1989) Effect of thyroid hormones on glucokinase gene transcription in rat liver, f, Biol, Client- 264, 20643-20647-Kaptein, E. M. (1996). Thyroid hormone metabolism and thyroid diseases in chronic renal failure. Ernlocr. Rev. 17, 45-65... 

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