INDEX thyroid hormones

Hypothyroid women frequently have anovulatory cycles and are therefore relatively infertile until restoration of the euthyroid state. This has led to the widespread use of thyroid hormone for infertility, although there is no evidence for its usefulness in infertile euthyroid patients. In a pregnant hypothyroid patient receiving thyroxine, it is extremely important that the daily dose of thyroxine be adequate because early development of the fetal brain depends on maternal thyroxine. In many hypothyroid patients, a modest increase in the thyroxine dose (about 20-30%) is required to normalize the serum TSH level during pregnancy. Because of the elevated maternal TBG, the free thyroxine index (FT4I) or free thyroxine (FT4) and TSH (Table 38-2) must be used to monitor maternal thyroxine dosages. 

The THBR is derived from a version of the T3 or T4 uptake test. Uptake tests are used to estimate the number of unoccupied (unsaturated) thyroid hormone bindhig sites on serum proteins. This information is important because variations in total thyroid hormone concentrations in blood, as discussed previously, have resulted from changes in binding protein concentrations. Values obtained by uptake methods are expressed as a THBR, which is directly proportional to the free hormone fraction (within limits). Measurement of THBR, in conjunction with a total hormone concentration, is a clinically useful indirect method for calculating the FT4 (or FT3) index. The index approach is particularly useful in patients with nonthyroidal illness in whom FT4 immunoassay methodologies are unreliable. Specifically, TT4 measurement is more diagnostically useful in such patients provided that values are interpreted in accord with the severity of illness in the patient that is indirectly reflected by abnormalities in THBR. 

Faix JC, Rosen HN, Valazquez FR. Indirect estimation of thyroid hormone-binding proteins to calculate free thyroxine index comparison of iionisotopic methods that use labeled thyroxine ( T-Uptake ). Cfin Chem 1995 41 41-7. 

Eales, J.G., S.B. Brown, D.G. Cyr, B.A. Adams and K.R. Finnson. Deiodination as an index of chemical disruption of thyroid hormone homeostasis and thyroidal status in fish. In Environmental Toxicology and Risk Assessment Standardization of Biomarkers for Endocrine Disruption and Environmental Assessment Eighth Volume, ASTM STP 1364, edited by D.S. Henshel, M.C. Black and M.C. Harrass, West Conshohocken, PA, American Society for Testing and Materials, pp. 136-164, 1999. 

Cardiovascular Effects Thyroid hormones directly and indirectly influence cardiac function, and cardiovascular manifestations are prominent clinical consequences of thyroid disease. In hyperthyroidism, there is tachycardia, increased stroke volume, increased cardiac index, cardiac hypertrophy, decreased peripheral vascular resistance, and increased pulse pressure. In hypothyroidism, there is bradycardia, decreased cardiac index, pericardial effusion, increased peripheral vascular resistance, decreased pulse pressure, and elevation of mean arterial pressure. 

The synthetic preparations used are the sodium salts of the natural isomers of the thyroid hormones. Levothyroxine sodium (L-T, synthroid, levoxyl, levothroid, unithroid, others) is available in tablets in a variety of doses and as a lyophilized powder for injection. L-T has a narrow therapeutic index, and the FDA has mandated demonstration of bioequivalence for brand and generic preparations by the various producers. Liothyronine sodium (L-Tft is available in tablets (cytomel) and in an injectable form (triostat). A mixture of L-T and L-T is marketed as liotrix (thyroiar). Desiccated thyroid preparations, derived from whole animal thyroids and containing both T and T have highly variable biologic activity and are much less desirable. 

One of the most frequent questions asked has been whether or not pure ID results in hypothyroidism (Morreale de Escobar et ai, 1997). The answer to this is especially difficult, because there are few quantitative indices of thyroid hormone action in different tissues. For this reason, we have focused on concentrations of 3,5,3 -triiodo-L-thyronine (T3), which was taken as an index of possible thyroid hormone effectiveness at the individual tissue level, as discussed elsewhere (Escobar-Morreale et ai, 1995). As will be seen, the thyroid status of rats with ID cannot be defined for the animal as a whole, because it is eminently tissue specific At all grades of ID, elevated. 

Erion MD, Cable EE, Ito BR, Jiang H, Fujitaki JM, Finn PD, Zhang BH, Hou J, Boyer SH, van Poelje PD et al (2007) Targeting thyroid hormone receptor-beta agonists to the liver reduces cholesterol and triglycerides and improves the therapeutic index. Proc Natl Acad Sci USA 104 15490-15495... 

Boyer et al. synthesized and biologically evaluated a series of liver-selective phosphonic acids (PA) thyroid hormone receptor agonists (249) and their prodrugs to exploit the poor distribution of PA-based drugs to extrahepatic tissues and thereby to improve the therapeutic index. 

Kitamura S, Kato T, lida M et al (2005) Anti-thyroid hormonal activity of tetrabromobisphenol A, a flame retardant, and related compounds affinity to the mammalian thyroid hormone receptor, and effect on tadpole metamorphosis. Life Sci 18 1589-1601 Kuhn E, Arnet R, Kanzig A et al (2004) Bromierte flammschutzmittel in kunststoffprodukten des Schweizer marktes Swiss agency for the environment, forests and landscape. Bern, Switzerland. http //www.bafu.admin.ch/publikationen/publikation/00289/index.html lang=de. Accessed 01 May 2013... 

TSH, T3, T, T3-resin uptake, free thyroxin index), but careful attention to early signs and symptoms of hypofunction (e.g., weight gain, cold intolerance, hair loss) may be more productive. Thyroid-stimulating hormone is sensitive to early thyroid changes and, if elevated, should prompt treatment with thyroid supplements to avoid goiter or hypothyroidism. 

Thyroxin (tetraiodothyronine) is circulated in the blood in temporary union with blood proteins hence, what the chemical test actually measures is the protein-bound iodine content of the blood, which, in turn, serves as an index of relative activity of the thyroid in releasing its hormone into the blood—hence, the approximate basal metabolic rate. 

Presently, circulating T3, T4, and TSH are an adequate basis to assess the thyroid status. Because, T4 is highly boimd to proteins in serum (mainly TBG) it is necessary to consider the measurement of the free fraction of the hormone. In developed countries with a normal iodine intake most of the FT4 techniques perform similarly with the exception of particular situations (pregnant women, non-thyroidal illnesses). But, when iodine deficiency coexisted with nutritional problems, we experienced serious difficulties with most of the commercial assays. In our hands, the FT4 index calculated as the ratio of T4 to TBG is the most appropriate tool. 

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