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Chemical Compound Review

Euthyrox     (2S)-2-amino-3-[4-(4-hydroxy- 3,5-diiodo...

Synonyms: eltroxin, thyroxin, Eutirox, Levoxyl, Oroxine, ...
 
 
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Disease relevance of Thyrax

  • The estimation of T4 values supplemented by measurement of TSH values on specimens with low T4 values has proved to be a satisfactory approach to large-scale screening for congenital hypothyroidism [1].
  • We conclude that T4 and T3 can directly stimulate bone resorption in vitro at concentrations approaching those which occur in thyrotoxicosis [2].
  • We conclude that intrathyroidal T4 to T3 conversion by D2 may contribute significantly to the relative increase in thyroidal T3 production in patients with Graves' disease, toxic adenomas, and, perhaps, iodine deficiency [3].
  • Histological examination revealed a marked thyroiditis in hTg-only animals and a significantly reduced degree of mononuclear cell infiltration and follicular destruction in the M plus T4-treated groups (graded 1.9 compared with 3.6 in hTg-only P = less than 0.01) [4].
  • In 4 of the patients in whom clinical and biochemical evidence of hypothyroidism persisted 6 months postoperatively, long-term T4 replacement therapy was instituted [5].
  • Long-term levothyroxine treatment in young adults with congenital hypothyroidism is associated with impaired diastolic function and exercise capacity and increased intima-media thickness [6].
 

Psychiatry related information on Thyrax

  • Four patients had high serum thyroxine (T4) concentrations during periods of heavy amphetamine abuse [7].
  • Surprisingly, the small changes in the severity of the depressive symptoms in the group as a whole were significantly correlated to the changes in the serum levels of T4 during the weeks of bright- and dim-light treatment, respectively [8].
  • Clinical signs of hypometabolism in anorexia nervosa may result from the "low triiodothyronine syndrome," in which thyroxine (T4) and thyroid stimulating hormone are usually normal, but triiodothyronine (T3) is in a range compatible with hypothyroidism [9].
  • When pre-treatment food restriction, oral contraceptive use and binge frequency where controlled for, low T4 concentration was the only predictor of eating disorder diagnosis at follow-up [10].
  • Severity of withdrawal symptoms was negatively correlated with the total T4 levels after 8 days of abstinence [11].
 

High impact information on Thyrax

  • Mc3r(-/-) mice did not have significantly altered corticosterone or total thyroxine (T4) levels [12].
  • When a patient with an increased serum TBG concentration becomes thyrotoxic, the T4 level rises further and the resin T3 uptake increases from low into the normal range [13].
  • 5'DI-deficient mice had twofold higher serum free T4 but normal free T3 and thyrotropin [14].
  • Exogenous T4 increased food intake by 20% in sarcoma-bearing mice [15].
  • The benefit of this was probably counteracted by an increased metabolic rate, since reversal of plasma levels of T3 and free T4 had no net effect on body composition of freely eating sarcoma-bearing mice, although it had a negative effect on body and muscle composition in food-restricted controls [15].
 

Chemical compound and disease context of Thyrax

  • Mild clinical hypothyroidism associated with low levels of serum total thyroxine (T4) and tri-iodothyronine (T3) and raised levels of serum thyroid-stimulating hormone (T.S.H.) has been observed in 14 of 40 patients (35%) in the early months after a subtotal thyroidectomy for thyrotoxicosis under cover of propranolol [5].
  • The data indicate that GH has dramatic influences on the tumors and, when GH, cortisone, and T4 are administered together, these hormones have a synergistic effect on the growth of the Swarm rat chondrosarcoma [16].
  • Free T4 was higher in the subgroup of patients with a multinodular goiter and a decreased TSH response to thyrotropin-releasing hormone [17].
  • Sodium ipodate appears to alter peripheral T4 metabolism and, in addition, produces thyroid-inhibiting effects in hyperthyroidism [18].
  • The low T4, free T4, and TSH concentrations and normal TSH responses to TRH found in these infants are characteristic of hypothalamic (tertiary) hypothyroidism, but differ from classic tertiary hypothyroidism in that the disorder was transient [19].
 

Biological context of Thyrax

  • Patients showed diminished T4 binding sites rather than increased total T4 [20].
  • This difference is because of the conversion of T4 to T3 in target cells of the tadpole catalyzed by the enzyme type II iodothyronine deiodinase (D2) and the local effect (cell autonomy) of this activity [21].
  • Hypothalamic autoregulation of T4 influx may constitute a critical cellular process involved in the generation and expression of seasonal reproductive rhythms and suggests a previously undescribed mechanism by which neural targets gain access to peripheral hormones [22].
  • Down-regulation of these genes was associated with reduced hypothalamic T4 uptake, which was reversed by long-day photoperiod treatments that restored responsiveness to short days [22].
  • Physiological concentrations of T3 but not T4 can suppress thyrotropin subunit beta gene expression [21].
 

Anatomical context of Thyrax

  • These data and those on the relative proportion of rT3, T3, and T4 in 10 thyroid glands were used to assess the significance of the contribution of thyroidal secretion to PR-rT3 and PR-T3 [23].
  • At 4 h of age the mean serum rT3 concentration (165 plus or minus 13 ng per 100 ml) in six newborns was 4ot significantly different from that in paired cord blood samples (194 plus or minus 25 ng per 100 ml); on the other hand, whenever, studied, the mean serum T3 and T4 levels were significantly higher at 4 h than at birth [24].
  • Down-regulation of genes encoding T4-binding proteins in the hypothalamus during this interval may restrict access of a static T4 signal to hypothalamic target tissues that regulate reproduction, thereby timing annual transitions in reproductive function [22].
  • Treatment of cardiac fibroblasts in culture (10 nM L-thyroxin) resulted in a 33% (p less than 0.005) decrease in the abundance of mRNA for pro alpha 2(I) collagen [25].
  • As the uptake of T4 and T3 depends on the presence of a sodium gradient over the plasma membrane, the inhibitory potency of ER-22 on the Na+,K+-ATPase activity was investigated [26].
 

Associations of Thyrax with other chemical compounds

 

Gene context of Thyrax

  • In renal cortex, SOD activity was decreased in the T4-75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T4-treated groups [30].
  • The abnormalities observed in the Pit1dw-J homozygote mouse seem to be caused by both direct and indirect effects of the deficiency of TSH (or T4), PRL, or GH rather than by a direct effect of the deletion of Pit1 [31].
  • The development of a low (<1 ng/mL) serum Tg (on LT4 therapy) by the second postoperative year signifies a low 5-year recurrence risk whereas a rising serum Tg in the face of TSH suppression is an abnormal response consistent with recurrence [32].
  • The T4-binding studies also demonstrated the presence of hybrid tetramers between mouse and human TTR subunits in the ttr+/+ transgenic mice expressing 6.0-hMet 30 [27].
  • Serum PRL concentrations in the basal state were decreased, as were levels of triiodothyronine (T3), thyroxine (T4), and free T4 index [33].
 

Analytical, diagnostic and therapeutic context of Thyrax

  • Control animals that received concurrent T4 administration alone showed similar hTg-induced murine thyroiditis to non-T4-treated animals and could not explain the apparent immunosuppression observed [4].
  • The values (mean +/- 2 SD) for urinary T4 were 24.3 +/- 20.3 in the patient group and 1.5 +/- 0.7 microgram/24 h in the control group [34].
  • After treatment, serum alkaline phosphatase levels rose as T4 levels declined; at 3 months, the mean serum alkaline phosphatase value rose from 7.1 Bodansky units to 10.3 Bodansky units (P less than 0.005), while the mean T4 value fell from 18 microgram/dl to 7.2 microgram/dl (P less than 0.005) [35].
  • Basal plasma levels of thyroxine (T4), triiodothyronine (T3) and reverse T3 were determined by radioimmunoassay in 44 control subjects, 44 Type 1 (insulin-dependent) and 39 Type 2 (non insulin-dependent) diabetic patients aged from 15 to 75 years [36].
  • Underestimates of serum free thyroxine (T4) concentrations by free T4 immunoassays [37].

References

  1. Screening for congenital hypothyroidism. Results in the newborn population of New England. Mitchell, M.L., Larsen, P.R., Levy, H.L., Bennett, A.J., Madoff, M.A. JAMA (1978) [Pubmed]
  2. Direct stimulation of bone resorption by thyroid hormones. Mundy, G.R., Shapiro, J.L., Bandelin, J.G., Canalis, E.M., Raisz, L.G. J. Clin. Invest. (1976) [Pubmed]
  3. Type 2 iodothyronine deiodinase is highly expressed in human thyroid. Salvatore, D., Tu, H., Harney, J.W., Larsen, P.R. J. Clin. Invest. (1996) [Pubmed]
  4. Influence of methimazole on murine thyroiditis. Evidence for immunosuppression in vivo. Davies, T.F., Weiss, I., Gerber, M.A. J. Clin. Invest. (1984) [Pubmed]
  5. Temporary hypothyroidism after surgical treatment of thyrotoxicosis. Toft, A.D., Irvine, W.J., McIntosh, D., Seth, J., Cameron, E.H., Lidgard, G.P. Lancet (1976) [Pubmed]
  6. Long-term cardiovascular effects of levothyroxine therapy in young adults with congenital hypothyroidism. Salerno, M., Oliviero, U., Lettiero, T., Guardasole, V., Mattiacci, D.M., Saldamarco, L., Capalbo, D., Lucariello, A., Saccà, L., Cittadini, A. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  7. Amphetamine-induced hyperthyroxinemia. Morley, J.E., Shafer, R.B., Elson, M.K., Slag, M.F., Raleigh, M.J., Brammer, G.L., Yuwiler, A., Hershman, J.M. Ann. Intern. Med. (1980) [Pubmed]
  8. Serum concentrations of thyroid hormones in patients with nonseasonal affective disorders during treatment with bright and dim light. Baumgartner, A., Volz, H.P., Campos-Barros, A., Stieglitz, R.D., Mansmann, U., Mackert, A. Biol. Psychiatry (1996) [Pubmed]
  9. Anorexia nervosa with hyperthyroidism: case report. Byerley, B., Black, D.W., Grosser, B.I. The Journal of clinical psychiatry. (1983) [Pubmed]
  10. Thyroid indices and treatment outcome in bulimia nervosa. Gendall, K.A., Joyce, P.R., Carter, F.A., McIntosh, V.V., Bulik, C.M. Acta psychiatrica Scandinavica. (2003) [Pubmed]
  11. Long-term observation of the hypothalamic-pituitary-thyroid (HPT) axis in alcohol-dependent patients. Heinz, A., Bauer, M., Kuhn, S., Krüger, F., Gräf, K.J., Rommelspacher, H., Schmidt, L.G. Acta psychiatrica Scandinavica. (1996) [Pubmed]
  12. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Chen, A.S., Marsh, D.J., Trumbauer, M.E., Frazier, E.G., Guan, X.M., Yu, H., Rosenblum, C.I., Vongs, A., Feng, Y., Cao, L., Metzger, J.M., Strack, A.M., Camacho, R.E., Mellin, T.N., Nunes, C.N., Min, W., Fisher, J., Gopal-Truter, S., MacIntyre, D.E., Chen, H.Y., Van der Ploeg, L.H. Nat. Genet. (2000) [Pubmed]
  13. Remission of hyperthyroidims and oral contraceptive therapy. [Answer to question]. Selenkow, H.A. JAMA (1984) [Pubmed]
  14. Physiological and genetic analyses of inbred mouse strains with a type I iodothyronine 5' deiodinase deficiency. Berry, M.J., Grieco, D., Taylor, B.A., Maia, A.L., Kieffer, J.D., Beamer, W., Glover, E., Poland, A., Larsen, P.R. J. Clin. Invest. (1993) [Pubmed]
  15. Thyroid hormones and experimental cancer cachexia. Svaninger, G., Lundberg, P.A., Lundholm, K. J. Natl. Cancer Inst. (1986) [Pubmed]
  16. Hormone responsiveness of a transplantable rat chondrosarcoma: III. ultrastructural evidence of in vivo hormone dependence. McCumbee, W.D., Lebovitz, H.E., McCarty, K.S. Am. J. Pathol. (1981) [Pubmed]
  17. Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic nontoxic goiter. Berghout, A., Wiersinga, W.M., Smits, N.J., Touber, J.L. Am. J. Med. (1990) [Pubmed]
  18. Changes in circulating iodothyronines in euthyroid and hyperthyroid subjects given ipodate (Oragrafin), an agent for oral cholecystography. Wu, S.Y., Chopra, I.J., Solomon, D.H., Bennett, L.R. J. Clin. Endocrinol. Metab. (1978) [Pubmed]
  19. Significance of transient postnatal hypothyroxinemia in premature infants with and without respiratory distress syndrome. Hadeed, A.J., Asay, L.D., Klein, A.H., Fisher, D.A. Pediatrics (1981) [Pubmed]
  20. Behavioral and endocrine responses of schizophrenic patients to TRH (protirelin). Prange, A.J., Loosen, P.T., Wilson, I.C., Meltzer, H.Y., Fang, V.S. Arch. Gen. Psychiatry (1979) [Pubmed]
  21. Timing of metamorphosis and the onset of the negative feedback loop between the thyroid gland and the pituitary is controlled by type II iodothyronine deiodinase in Xenopus laevis. Huang, H., Cai, L., Remo, B.F., Brown, D.D. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  22. Hypothalamic gene expression in reproductively photoresponsive and photorefractory Siberian hamsters. Prendergast, B.J., Mosinger, B., Kolattukudy, P.E., Nelson, R.J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  23. An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man. Chopra, I.J. J. Clin. Invest. (1976) [Pubmed]
  24. Circulating 3,3', 5'-triiodothyronine (reverse T3) in the human newborn. Chopra, I.J., Sack, J., Fisher, D.A. J. Clin. Invest. (1975) [Pubmed]
  25. Decreased collagen gene expression and absence of fibrosis in thyroid hormone-induced myocardial hypertrophy. Response of cardiac fibroblasts to thyroid hormone in vitro. Yao, J., Eghbali, M. Circ. Res. (1992) [Pubmed]
  26. Inhibition of iodothyronine transport into rat liver cells by a monoclonal antibody. Mol, J.A., Krenning, E.P., Docter, R., Rozing, J., Hennemann, G. J. Biol. Chem. (1986) [Pubmed]
  27. Analysis of amyloid deposition in a transgenic mouse model of homozygous familial amyloidotic polyneuropathy. Kohno, K., Palha, J.A., Miyakawa, K., Saraiva, M.J., Ito, S., Mabuchi, T., Blaner, W.S., Iijima, H., Tsukahara, S., Episkopou, V., Gottesman, M.E., Shimada, K., Takahashi, K., Yamamura, K., Maeda, S. Am. J. Pathol. (1997) [Pubmed]
  28. Impaired atrial natriuretic factor systemic clearance contributes to its higher levels in uremia. Paniagua, R., Franco, M., Rodriguez, E., Sanchez, G., Morales, G., Herrera-Acosta, J. J. Am. Soc. Nephrol. (1992) [Pubmed]
  29. The failure of physiologic doses of reverse T3 to effect thyroid-pituitary function in man. Nicod, P., Burger, A., Strauch, G., Vagenakis, A.G., Braverman, L.E. J. Clin. Endocrinol. Metab. (1976) [Pubmed]
  30. Cardiac and renal antioxidant enzymes and effects of tempol in hyperthyroid rats. Moreno, J.M., Rodríguez Gómez, I., Wangensteen, R., Osuna, A., Bueno, P., Vargas, F. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  31. Cerebellar microfolia and other abnormalities of neuronal growth, migration, and lamination in the Pit1dw-J homozygote mutant mouse. Sekiguchi, M., Abe, H., Moriya, M., Tanaka, O., Nowakowski, R.S. J. Comp. Neurol. (1998) [Pubmed]
  32. Detection of residual and recurrent differentiated thyroid carcinoma by serum thyroglobulin measurement. Spencer, C.A., LoPresti, J.S., Fatemi, S., Nicoloff, J.T. Thyroid (1999) [Pubmed]
  33. Induction of hypothyroidism and hypoprolactinemia by growth hormone producing rat pituitary tumors. Seo, H., Refetoff, S., Fang, V.S. Endocrinology (1977) [Pubmed]
  34. Thyroid function studies in the nephrotic syndrome. Afrasiabi, M.A., Vaziri, N.D., Gwinup, G., Mays, D.M., Barton, C.H., Ness, R.L., Valenta, L.J. Ann. Intern. Med. (1979) [Pubmed]
  35. Alkaline phosphatase isoenzyme patterns in hyperthyroidism. Cooper, D.S., Kaplan, M.M., Ridgway, E.C., Maloof, F., Daniels, G.H. Ann. Intern. Med. (1979) [Pubmed]
  36. Effect of diabetic control on the level of circulating thyroid hormones. Schlienger, J.L., Anceau, A., Chabrier, G., North, M.L., Stephan, F. Diabetologia (1982) [Pubmed]
  37. Underestimates of serum free thyroxine (T4) concentrations by free T4 immunoassays. Nelson, J.C., Weiss, R.M., Wilcox, R.B. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
 
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