Metabolism of thyroid hormones

There are several ways by which TSH secretion can be increased. An increased hepatic enzyme activity may cause an increased metabolism of thyroid hormones, leading to lower semm hormone levels, which in mm leads to increased secretion of TRH, and subsequently increased TSH secretion. Regarding human relevance, the pathways for regulation of the hypothalamo-pituitary-thyroid axis of rats and humans are similar and the mechanism is relevant for humans, but the human system is far more resistant to perturbation. 

BIOSYNTHESIS, STORAGE, SECRETION, AND METABOLISM OF THYROID HORMONES... 

Following receipt of data the Commission drew up priority lists of substances that, on the basis of that data, were thought to have the potential to pose a risk of harm to human health or the environment. By the publication of the EU White Paper in 2001, four lists, containing a total of 141 substances, had been adopted by the relevant technical committee (CEC, 2001). The progress of these risk assessments was very slow. Risk assessment of hexabromocyclododecane (HBCD), for example, commenced in 1997 but was still not completed nine years later (ENDS, 2006). In 2006 around 16,700 tonnes of HBCD were produced every year for use as a flame retardant. It may have neurotoxic effects and interfere with the metabolism of thyroid hormone, but because risk assessment of it had not reached a conclusion there were no restrictions on its use. By 2006 final risk assessment reports were available for only about 70 substances (European Commission, 2006b) — less than 0.5 per cent of the 30,000 or so existing substances on the European market at quantities of above 1 tonne per annum. 

The most clearly documented role lor selenium is as a necessary component of glutathione peroxidase. Selenium is also involved in the functions of additional enzymes, e.g.. type I iodoihvronine deiodinase. leukocyte acid phosphatase, and glucuronidases. A role for selenium in electron transfer has been suggested as has involvement in nonheme iron proteins. Selenium and vitamin b appear to be necessary lor proper functioning of lysosomal membranes. A role for selenium in metabolism of thyroid hormone has been continued. 

Burger A, Dinichert D, Nicod P, Jenny M, Lemarchand-Beraud T, Vallotton MB. Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxin, and thyrotropin. A drug influencing peripheral metabolism of thyroid hormones. J Clin Invest 1976 58(2) 255-9. 

Some diseases (liver disease, kidney disease, and malnutrition) interfere with the transport or metabolism of thyroid hormones and thereby alter thyroid function tests. 

Several drugs (for example amiodarone, androgens, glucocorticoids, phenytoin, and salicylates) interfere with the transport or metabolism of thyroid hormones and thereby alter thyroid function tests. These have been reviewed (90). In patients taking levothyroxine serum TSH rises after treatment with sertraline (91) and antimalarial prophylaxis with chloroquine and proguanil... 

Thyroid hormone activity is determined predominantly by intracellular concentrations of (free) T3 in the tissues. This T3 bioavailability depends on 1) the secretion of T4 and T3 by the thyroid, 2) the conversion of T4 to T3 outside the thyroid, 3) the metabolic clearance of T3 and 4) exchange of T4 and T3 between plasma and tissues. It is the purpose of this chapter to review recent advancements in the study of the transport and metabolism of thyroid hormone. Especially the role of deiodination, conjugation and tissue uptake mechanisms will be emphasized in the regulation of thyroid hormone action. 

Figure 5 is a model of the peripheral metabolism of thyroid hormone in normal humans which places the production of plasma T3 and the clearance of plasma rT3 predominantly in tissues with PTU-sensitive, type I deiodinase activity. Although the role of the liver is emphasized, contribution of the kidneys is not excluded. Clearance of plasma T3 and production of plasma rT3 is located mainly in tissues such as brain and perhaps skin with PTU-insensitive, type III deiodinase activity. 

There are many reviews available on the biochemistry of thyroid hormones27-30 including the excellent review by Doonan in this Series1. Biosynthesis and metabolism of thyroid hormones will be reviewed briefly in this chapter. Attention will be given to recent developments relating to the mechanisms responsible for the physiological responses to thyroid hormones. 

Riboflavin may also be involved in the metabolism of thyroid hormones. In the presence of oxygen, riboflavin phosphate catalyzes a photolytic deiod-ination of thyroxine. The lower tissue concentration of riboflavin phosphate in hypothyroidism may thus serve to protect such thyroid hormone as is available against catabolism and prolong its action. 

Thyroid hormones are used either to replace the failing function of the thyroid gland (spontaneous or drug-induced) or to suppress the endocrine function of abnormal thyroid tissues (especially non-toxic struma or goiter or after thyroidectomy for thyroid neoplasms). Although there are abnormalities of the peripheral metabolism of thyroid hormones in some forms of undernutrition or overnutrition, thyroid drug therapy cannot be considered a safe way of treating obesity. 

Eder K, Kralik A, Kirchgebner M. 1995. [Influence of deficient to subtoxic selenium intake on metabolism of thyroid hormones], Z Emahrungswiss 34 277-283. (German)... 

Some organochlorine chemicals (including some pesticides and industrial by-products, such as polychlorinated biphenyls [PCBs] and hexachlorobenzene) may interfere with the metabolism of thyroid hormones (Brouwer et al., 1999 Sala et al., 2001). 

Visser, TJ. (1990). Importance of deiodination and conjugation in the hepatic metabolism of thyroid hormone. In (ed. M.A. Greer), The Thyroid Gland. Raven Press, New York, NY, pp. 233-269. 

Chopra IJ, Solomon DH, Chopra U, et al. Pathways of metabolism of thyroid hormones. Recent Prog Horm Res 1978 34 521-567. 

Licastro F, Mocchegiani E, Zannotti M, et al. 1992. Zinc affects the metabolism of thyroid hormones in children with Down s Syndrome Normalization of thyroid stimulating hormone and of reversal triiodothyronine plasmic levels by dietary zinc supplementation. Int J Neurosci 65(1-4) 259-268. (Retrieval in progress)... 

Chen, M.D., A.K. Kuang, and J.L. Chen. 1989. Influence of yang-restoring herb medicines upon metabolism of thyroid hormone in normal rats and a dmg administration schedule. Zheng Xi Yi ieHeZaZhi9 2) 93-95. 

In the early 70 s, when different approaches to studying these problems experimentally were considered, the distribution of thyroid hormones in the brain had not yet been systematically examined. Since that time a number of studies have addressed the issue of regional, cellular and sub-cellular localization and metabolism of thyroid hormones in brain (7-9). 

Kaplan, M.M. (1983) Metabolism of thyroid hormones. In Congenital Hypothyroidism (Dussault JH and Walker P, Eds), Marcel Dekker Inc., New York, pp 11-35. 

Woods RJ, Sinha AK, Ekins R, Uptake and metabolism of thyroid hormones by the rat foetus in early pregnancy, Clin Sci 67 359 (1984)... 

Fig. 8-5. Effects of drugs and inborn errors on the metabolism of thyroid hormones...

In the human, TTR is one of three plasma proteins involved in the transport of the thyroid hormones in blood (Ingbar, 1963 Oppenheimer, 1968). The principal transport protein for thyroid hormones in human plasma is thyroxine-binding globulin, and TTR plays only a lesser role in the normal transport and metabolism of thyroid hormones in man (Woeber and Ingbar, 1968). In the rat, however, TTR appears to be the major thyroid hormone transport protein (Davis et al., 1970 Sutherland and Brandon, 1976). 

Endocrine Hypothyroidism and altered metabolism of thyroid hormones have been reported as adverse events in neonates and children, resulting from the use of antiseptics containing povidone-iodine [SED-15, 1896 SEDA-30, 279 SEDA-31, 411 SEDA-32, 440]. Because of concerns about possible iodine excess, chlorhexidine-based antiseptics have replaced povidone-iodine in some clinical settings. However, this may not be advantageous for infants and children who are receiving total parenteral nutrition (TPN) as iodine is not routinely added to TPN solutions. Previously, iodine deficiency was considered unlikely in patients receiving TPN, because of adsorption from iodine-containing skin disinfectants and other adventitious sources [67 68 ]. 

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