Thyroid hormones physiology

Mastorakos G, Karoutsou El, Mlzamtsidi M, Creatsas G (2007) The menace of endocrine disrupters on thyroid hormone physiology and their impact on intrauterine development. Endocrine 31 219-237... 

Fisher DA. Physiological variations in thyroid hormones physiological and pathophysiological considerations. Clin Chem 1996 42 135-9. 

In higher organisms a portion of the tyrosine is metabolized via the thyroid hormones. Physiologically these are highly active substances, and the amount of tyrosine metabolized by this pathway is probably relatively small. However, no quantitative figures appear to be available. 

Whereas some of the recent advances in thyroid function tests have been necessitated by the new concepts of thyroid hormone physiology, others have been secondary to major technological advances in clinical chemistry, in particular the introduction of radioimmunoassay (RIA). 

Among vertebrate species, the neuro-endocrine-immime system is responsible for many complex, inter-related physiological processes including neuronal, homeostatic, reproductive and immune functions. There are four main types of hormone polypeptides, eicosanoids, steroids and thyroid hormones. Reflecting the inter-dependency of the neiiro-endocrine and immune systems, hormones, neuropeptides and other neiirotransmitters are known to be produced by some immune cells and play a role in the regulation of the immune system, while endocrine and nervous tissues express receptors for many substances produced by the immune system. The major focus of interest in endocrine disruption has... 

The TAAR receptor system has also been associated with body temperature regulation on the basis of putative thyroid hormone metabolites and their synthetic derivatives (thyronamines) activating TAAR1 in rodents. However, as these effects are only observed with thyronamine concentrations several orders of magnitude above physiological levels, and as the specificity of these compounds has not been determined, the physiological significance of these observations is unclear. 

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)... 

Most of the physiologic activity of thyroid hormones is from the actions of T3. T4 can be thought of primarily as a prohormone. Eighty percent of needed T3 is derived from the conversion of T4 to T3 in peripheral tissue under the influence of tissue deiodinases. These deiodinases allow end organs to produce the amount of T3 needed to control local metabolic functions. These enzymes also catabolize T3 and T4 to biologically inactive metabolites. Thyroid hormones bind to intracellular receptors and regulate the transcription of various genes. 

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 ... 

Vasudevan N, Ogawa S, Pfaff D (2002) Estrogen and thyroid hormone receptor interactions physiological flexibility by molecular specificity. Physiol Rev 82 923... 

Retinoids are a family of naturally occurring and synthetic analogues of vitamin A. The skin of subjects deficient in vitamin A becomes hyperplastic and keratotic (phrynoderma, or toad skin). While natural vitamin A is occasionally employed therapeutically, synthetic retinoids are more effective and represent a major advance in dermatological pharmacotherapy. Retinoids have myriad effects on cellular differentiation and proliferation it is likely that nuclear retinoic acid receptors mediate these effects by activating gene expression in a manner analogous to receptors for steroid hormones and thyroid hormones. Despite a common mechanism of action, however, retinoids vary widely in their physiological effects. 

A second dietary trace element, selenium, is also essential for normal thyroid hormone metabohsm. Selenium in the form of selenocysteine is a required component for three enzymes that remove iodide from thyroid hormones. Deiodination is the major metabohc pathway by which T4 and T3 are cleared from the system. After secretion by the thyroid gland, T4 may be deiodinated to yield either T3 or the physiologically inactive reverse Tj (3,3, 5 -triiodothyronine, or rX3). T3 and rTj are further deiodinated to form less active metabolites. Selenium, like iodine, is deficient in many areas of the world. 

The T4 and T3 that are released from the thyroid gland are firmly but reversibly bound to several plasma proteins. More than 99% of the circulating thyroid hormone is protein bound, with only the free hormone available to enter cells (Table 65.1).The amount of T4 or Tj entering the cells and the ultimate physiological response are directly related to the plasma concentrations of free T4 and free Tj It is the concentrations of free T4 and T3 in the plasma that are regulated by the HPTA (Fig. 65.2) rather than the total (i.e., free plus protein-bound) plasma T4 and Tj concentrations. 

Hypothyroidism refers to the exposure of body tissues to a subnormal amount of thyroid hormone. This can result from a defect anywhere in the HPTA. As a consequence of the lack of thyroid hormone, a wide variety of physiological and clinical disturbances involving virtually every organ system may result. 

Most attempts of using hormones as psychotropic medications were conducted with gonadal or with thyroid hormones, mainly because of the apparent mood changes associated with physiological or disorder-associated changes in levels or activity of these hormones. However, as shown in Table 17-1, current applications are broader and involve several hormones and systems. It is anticipated that, with acquired knowledge on mood effects of several other hormones, that list will continue to expand. Here, I focus on psychotropic effects of gonadal and thyroid hormones. Cortisol and melatonin are only briefly discussed. 

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. 

Physiologic Function Testing, An example of this application is the assay of thyroid hormone levels in (lie blood winch, in turn, can aid in the assessment of thyroid function. The radioactive iodine uptake test, which involves the administration of a dose of l31l (iodine-131) to the patient, is also a valuable procedure in assessing thyroid function. At present, the technique is best reserved for problem cases rather than used as a primary screening test. The main disadvantage of this test is the effect of the dietary intake of iodine, which reacts in various ways in different individuals. 

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