Thyroxine physiology

Murkin JM. Anesthesia and hypothyroidism a review of thyroxine physiology, pharmacology, and anesthetic implications. Anesth Analg 1982 61(4) 371-83. 

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)... 

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 ... 

Thyroid gland secretes two important hormones, thyroxine (TJ and triiodothyronine (Tj). The third hormone, calcitonin secreted from interstitial cells is physiologically different and is responsible for the regulation of calcium metabolism. 

T4 and T3 in plasma are reversibly bound to protein, primarily thyroxine-binding globulin (TBG). Only about 0.04% of total T4 and 0.4% of T3 exist in the free form. Many physiologic and pathologic states and drugs affect T4, T3, and thyroid transport. However, the actual levels of free hormone generally remain normal, reflecting feedback control. 

Albumin is a major transport facilitator of hydrophobic compounds which would otherwise disrupt cellular membranes. These compounds include free fatty acids and bilirubin as well as hormones such as cortisol, aldosterone, and thyroxine when these materials have exceeded the capacity of proteins normally associated with them. Albumin also binds ions, including toxic heavy metals and metals such as copper and zinc which are essential for normal physiological functioning but may be toxic in quantities in excess of their binding capacity for their carrier proteins. Binding of protons is the basis for the buffering capacity of albumin. 

There is no such clear cut difTcrcnlialiun as metamorphosis in the mammal, but development is an extremely complex process and has been shown to depend upon the presence of adequate amounts of thyroid hormones. Deficient development, especially of the central nervous system, is marked in ehildren suffering from thyroid deficiency early in life, ansi this inadequacy cannot be overcome completely by medication commenced after the first few weeks. In the adult, thyroxine is important in the maintenance of energy turnover in most of the tissues of the body, such as the heart, skeletal muscle, liver, and kidney, Other physiological functions, most notably brain aclivity and reproduction, are also dependent upon thyroxine, although the metabolic rales of the tissues concerned in these functions do not seem to be altered. 

When replacement therapy is with levothyroxine only, the T4/T3 ratio is increased compared with healthy subjects, suggesting that thyroid secretion of T3 is physiologically important. Animal studies have shown that euthyroidism is not restored in all tissues by levothyroxine alone (13). Mood and neuropsychological function improved in hypothyroid patients when 50 micrograms of thyroxine was replaced by 12.5 micrograms of liothyr-onine (14). 

Several studies have failed to confirm the benefits of combined levothyroxine and liothyroninc therapy. Liothyroninc given once a day results in non-physiologi-cal peak serum concentrations of T3. Modified-release triiodothyronine plus thyroxine can normalize serum biochemistry, but it is not known whether this formulation is superior to levothyroxine alone (15). 

This case illustrates the need to verify apparently severe reactions to thyroxine, since such reactions are physiologically unlikely, given that exogenous thyroxine is structurally identical to that produced endogenously. 

Bauer M, Baur H, Berghofer A, Strohle A, Hellweg R, Muller-Oerlinghausen B, Baumgartner A. Effects of supra-physiological thyroxine administration in healthy controls and patients with depressive disorders. J Affect Disord 2002 68(2-3) 285-94. 

The many effects of lithium on thyroid physiology and on the hypothalamic-pituitary axis and their clinical impact (goiter, hypothyroidism, and hyperthyroidism) have been reviewed (620). Lithium has a variety of effects on the hypothalamic-pituitary-thyroid axis, but it predominantly inhibits the release of thyroid hormone. It can also block the action of thyroid stimulating hormone (TSH) and enhance the peripheral degradation of thyroxine (620). Most patients have enough thyroid reserve to remain euthyroid during treatment, although some initially have modest rises in serum TSH that normalize over time. 

Because thyroxine contains four iodine residues, this compound is also referred to by the abbreviation T4. Likewise, triiodothyronine contains three iodine residues, hence the abbreviation T3. There has been considerable discussion about which hormone exerts the primary physiologic effects. Plasma levels of T4 are much higher than T3 levels, but T3 may exert most of the physiologic effects on various tissues, which suggests that T4 is a precursor to T3 and that the conversion of T4 to T3 occurs in peripheral tissues.23 Regardless of which hormone ultimately affects cellular metabolism, both T4 and T3 are needed for normal thyroid function. 

Lee, C.G. and Ip, Y.K. (1987). Environmental effect on plasma thyroxine (T4), 3,5,3 -triiodo-L-thyronine (T3), prolactin and cyclic adenosine 3 -5 -monophosphate (cAMP) content in the mudskippers Periophthalmus chrysospilos and Boleophthalmus boddaerti. Comparative Biochemistry and Physiology 87A, 1009-1014. 

Selenium is an essential trace element, being important in at least two critical enzymes, the antioxidant glutathione peroxidase (GPx), and type 1 iodothyronine deiodinase. GPx converts hydrogen peroxide to water, in the presence of reduced glutathione, while iodothyronine deiodinase catalyzes the conversion of thyroxine to triiodothyronine, the physiologically active hormone species. 

Inactive T4 converted to THY-R agonist T3 by Iodothyronine 5 -deiodinase (ITD) thyroxine synthesized by Edward Kendall (USA) (Nobel Prize, Physiology/Medicine, 1950, glucocorticoids, with T. Reichstein and ... 

Hormones are chemical substances which travel through the blood from one organ or tissue to another, and by catalytic action or in a similar w ay act as regulators of physiological activity. Some of the hormones, including thyroxine, are relatively simple chemical substances with knowm structure but many of them are very complex protein molecules, containing thousands of atoms per molecule. 

L-thyroxine (T j or tetraiodo-L-thyronine) and liothyronine (Tg or triiodo-L-thyronine) are the natural hormones of the thyroid gland. is a less active precursor of Tj, which is the major mediator of physiological effect. In this chapter for therapeutic use is referred to as levothyroxine (the rINN, see p. 83) rather than levothyroxine (the former usage). 

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