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The Efficacy of Thyroid Hormone Therapy in Brain-Dead Heart Donors: A Review of Thyroid Function in Health and Disease

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Abstract

In this chapter, we summarize thyroid hormone physiology as background to reviewing nonthyroidal disease syndrome in animals and humans. We then review the relationship between thyroid hormone regulation of the heart in health and disease. Finally, we review the basis for thyroid hormone treatment of cardiac dysfunction in brain-dead heart donors.

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References

  1. Warner MH, Beckett GJ. Mechanisms behind the non-thyroidal illness syndrome: an update. J Endocrinol. 2010;205:1–13.

    Article  PubMed  CAS  Google Scholar 

  2. Plikat K, Langgartner J, Buettner R, et al. Frequency and outcome if patients with nonthyroidal illness syndrome in a medical intensive care unit. Metabolism. 2007;56:239–44.

    Article  PubMed  CAS  Google Scholar 

  3. Peeters RP, Wouters PJ, van Toor H, Kaptein E, Visser TJ, van den Berghe G. Serum 3, 3′, 5′-triiodothyronine (rT3) and 3,5,3′-triiodothyronine/rT3 are prognostic markers in critically ill patients and are associated with post mortem tissue deiodinase activities. J Clin Endocrinol Metab. 2005;90:4559–65.

    Article  PubMed  CAS  Google Scholar 

  4. Leon-Sanz M, Lorente JA, Larrodera L, et al. Pituitary–thyroid function in patients with septic shock and its relation with outcome. Eur J Med Res. 1997;2:477–82.

    PubMed  CAS  Google Scholar 

  5. Alevizaki M, et al. Low triiodothyronine: a strong predictor of outcome in acute stroke patients. Eur J Clin Invest. 2007;37:651–7.

    Article  PubMed  CAS  Google Scholar 

  6. Gangemi EN, et al. Low triiodothyronine serum levels as a predictor of poor prognosis in burn patients. Burns. 2008;34:817–24.

    Article  PubMed  Google Scholar 

  7. Girvent M, Maestro S, Hernandz R, et al. Euthyroid sick syndrome: associated endocrine abnormalities and outcome in elderly patients undergoing emergency operation. Surgery. 1998;123:560–7.

    Article  PubMed  CAS  Google Scholar 

  8. Bermudez F, Surks MI, Oppenheimer JH. High incidence of decreased serum triiodothyronine concentration in patients with nonthyroidal disease. J Clin Endocrinol Metab. 1975;41:27–40.

    Article  PubMed  CAS  Google Scholar 

  9. Degroot LJ. Non-thyroidal illness syndrome is a manifestation of hypothalamic-pituitary dysfunction, and in view of current evidence, should be treated with appropriate replacement therapies. Crit Care Clin. 2006;22:57–86.

    Article  Google Scholar 

  10. Farwell AP. Thyroid hormone therapy is not indicated in the majority of patients with the sick euthyroid syndrome. Endocr Pract. 2008;14:1180–7.

    PubMed  Google Scholar 

  11. Lechan RM. The dilemma of the nonthyroidal illness syndrome. Acta Biomed. 2008;79:165–71.

    PubMed  CAS  Google Scholar 

  12. De Groot L. Dangerous dogmas in medicine: the nonthyroidal illness syndrome. JCEM. 1999;84:151–64.

    PubMed  Google Scholar 

  13. Stathatos N, Wartofsky L. The euthyroid sick syndrome: is there a physiologic rationale for thyroid hormone treatment? J Endocrinol Invest. 2003;26:1174–9.

    PubMed  CAS  Google Scholar 

  14. Peeters RP. Non thyroidal illness: to treat or not to treat? Ann Endocrinol (Paris). 2007;68:224–8.

    Article  CAS  Google Scholar 

  15. Maldonado LS, Murata GH, Hershman JM, Braunstein GD. Do thyroid function tests independently predict survival in the critically ill? Thyroid. 1992;2:119–23.

    Article  PubMed  CAS  Google Scholar 

  16. Brent G, Hershman. Thyroxine therapy in patients with severe nonthyroidal illnesses and low serum thyroxine concentration. JCEM. 1986;63:1–8.

    PubMed  CAS  Google Scholar 

  17. Novitzky D, Cooper DK, Rosendale JD, Kauffman HM. Hormonal therapy of the brain-dead organ donor: experimental and clinical studies. Transplantation. 2006;82:1396–401.

    Article  PubMed  CAS  Google Scholar 

  18. Taurog A. Hormone synthesis: thyroid iodine metabolism. In: Braverman LE, Utiger RD, editors. Werner and Ingbar’s the thyroid: a fundamental and clinical text. 7th ed. Philadelphia: Lippincott Williams and Wilkins; 1996. p. 47–80.

    Google Scholar 

  19. Dunn AD. Release and secretion of thyroid hormone. In: Braverman LE, Utiger RD, editors. Werner and Ingbar’s the thyroid: a fundamental and clinical text. 7th ed. Philadelphia: Lippincott Williams and Wilkins; 1996. p. 81–4.

    Google Scholar 

  20. St. German D, Galton V. The deiodinase family of selenoproteins. Thyroid. 1997;7:665–8.

    Google Scholar 

  21. Bianco AC, Kim BW. Deiodinases: implications of the local control of thyroid hormone action. J Clin Invest. 2006;116:2571–9.

    Article  PubMed  CAS  Google Scholar 

  22. Kaptein E, Robinson WJ, Grieb DA, Nicoloff JT. Peripheral serum thyroxine, triiodothyronine and reverse triiodothyronine kinectics in the low thyroxine state of acute nonthyroidal illness. J Clin Invest. 1982;69:526–35.

    Article  PubMed  CAS  Google Scholar 

  23. Schussler GC. The thyroxine-binding proteins. Thyroid. 2000;10:141–9.

    Article  PubMed  CAS  Google Scholar 

  24. Chopra IJ, Teco GN, Mead JF, Huang TS, Beredo A, Solomon DH. Relationship between serum free fatty acids and thyroid hormone binding inhibitor in nonthyroid illnesses. J Clin Endocrinol Metab. 1985;60: 980–4.

    Article  PubMed  CAS  Google Scholar 

  25. Jirasakuldech B, Schussler GC, Yap MG, Drew H, Josephson A, Michl J. A characteristic serpin cleavage product of thyroxine-binding globulin appears in sepsis sera. J Clin Endocrinol Metab. 2000;85:3996–9.

    Article  PubMed  CAS  Google Scholar 

  26. Surks MI, Hupart KH, Pan C, Shapiro LE. Normal free thyroxine in critical nonthyroidal illnesses measured by ultrafiltration of undiluted serum and equilibrium dialysis. Clin Endocrinol Metab. 1988;67:1031–9.

    Article  CAS  Google Scholar 

  27. Surks MI, Sievert R. Drugs and thyroid function. N Engl J Med. 1995;333:1688–94.

    Article  PubMed  CAS  Google Scholar 

  28. Silva JE, Dick TE, Larsen PR. The contribution of local tissue thyroxine monodeiodination to the nuclear 3, 5, 3′-triiodothyronine in pituitary, liver and kidney of euthyroid rats. Endocrinology. 1978;103:1196–207.

    Article  PubMed  CAS  Google Scholar 

  29. Mebis L, Debaveye Y, Ellger B, et al. Changes in the central component of the hypothalamus-pituitary-thyroid axis in a rabbit model of prolonged critical illness. Crit Care. 2009;13:R147.

    Article  PubMed  Google Scholar 

  30. Peeters R, et al. Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. J Clin Endocrinol Metab. 2003;88:3202–11.

    Article  PubMed  CAS  Google Scholar 

  31. Schwartz CE, May MM, Carpenter NJ, et al. Allan-Herndon-Dudley Syndrome and the monocarboxylate transporter 8 (MCT8) gene. Am J Hum Genet. 2005;77:41–53.

    Article  PubMed  CAS  Google Scholar 

  32. Mebis L, Paletta D, Debaveye Y, et al. Expression of thyroid hormone transporters during critical illness. Eur J Endocrinol. 2009;161:243–50.

    Article  PubMed  CAS  Google Scholar 

  33. Cheng SY, Leonard JL, Davis PJ. Molecular aspects of thyroid hormone actions. Endocr Rev. 2010;31:139–70.

    Article  PubMed  CAS  Google Scholar 

  34. Davis PJ, Davis BD. Nongenomic actions of thyroid hormone. Thyroid. 1996;6:497–504.

    Article  PubMed  CAS  Google Scholar 

  35. d’Amati G, di Gioia CR, Mentuccia D, et al. Increased expression of thyroid hormone receptor isoforms in end-stage human congestive heart failure. J Clin Endocrinol Metab. 2001;86:2080–4.

    Article  PubMed  Google Scholar 

  36. Ojamaa K, Klemperer JD, Klein I. Acute effects of thyroid hormone on vascular smooth muscle. Thyroid. 1996;6:505–12.

    Article  PubMed  CAS  Google Scholar 

  37. Napoli R, Guardasole V, Angelini V, et al. Acute effects of triiodothyronine on endothelial function in human subjects. J Clin Endocrinol Metab. 2007;92:250–4.

    Article  PubMed  CAS  Google Scholar 

  38. Surks MI, Grajower MM, Tai M, Defesi CR. Decreased hepatic nuclear L-triiodothronine receptors in rats and mice bearing transplantable neoplasms. Endocrinology. 1978;103:2234–9.

    Article  PubMed  CAS  Google Scholar 

  39. St. Germaine D, Galton VG. Comparative study of pituitary-thyroid hormone economy in fasting and hypothyroid rats. J Clin Invest. 1985;75:679–88.

    Article  Google Scholar 

  40. Hupart HK, Defesi CR, Katz PC, Shapiro LE, Surks MI. Differential response to L-triiodothyroine of anterior pituitary growth hormone messenger ribonucleic acid (mRNA) and beta-thyrotropin mRNA in a hypothyroid Walker 256 carcinoma-bearing rat model of nonthryoidal disease. Endocrinology. 1990;126: 616–21.

    Article  PubMed  CAS  Google Scholar 

  41. Davies TF, Yin X, Latif R. The genetics of the thyroid stimulating hormone receptor: history and relevance. Thyroid. 2010;20:727–36.

    Article  PubMed  CAS  Google Scholar 

  42. Silva LE, Biance SDC. Thyroid-adrenergic interactions: physiological and clinical implications. Thyroid. 2008;18:157–65.

    Article  PubMed  CAS  Google Scholar 

  43. Nicoloff JT, et al. The role of glucocorticoids in the regulation of thyroid function in man. J Clin Invest. 1970;49:1922.

    Article  PubMed  CAS  Google Scholar 

  44. Bianco AC, et al. The role of glucocorticoids in the stress induced reduction of extrathyroidal 3,5,3′-triiodotyronine generations in rats. Endocrinology. 1987;114:280–6.

    Google Scholar 

  45. Samuels H, Horowitz Z, Stanley F, Casanova J, Shapiro LE. Thyroid hormone controls glucocorticoid action in cultured GH1cells. Nature. 1977;286:254–7.

    Article  Google Scholar 

  46. Shapiro LE, Samuels HH, Yafee B. Thyroid hormone and glucocorticoid hormones synergistically control growth hormone mRNA in cultured GH1 cells. Proc Natl Acad Sci USA. 1978;75:45–9.

    Article  PubMed  CAS  Google Scholar 

  47. Shapiro LE, Sachchidananda J. Regulation of proteins by thyroid hormone and glucocorticoid: the response of hepatic α[alpha]2U globulin and pituitary growth hormone differ in adult male hypothyroid rats. Endocrinology. 1983;111:653–9.

    Article  Google Scholar 

  48. Prummel MF, et al. Ultra short-loop feedback control of thyrotropin secretion. Thyroid. 2004;14:825–9.

    Article  PubMed  CAS  Google Scholar 

  49. Hermus RM, et al. Continuous infusion of interleukin-1β[beta] induces a nonthyroidal illness syndrome in rat. Endocrinology. 1992;131:2139–46.

    Article  PubMed  CAS  Google Scholar 

  50. der Poll V, et al. Tumor necrosis factor: a putative mediator of the sick euthyroid syndrome in man. J Clin Endocrinol Metab. 1990;71:1567–72.

    Article  PubMed  Google Scholar 

  51. Boelen A, et al. Soluble cytokine receptors and the low 3,5,3′-triiodothyronine syndrome in patients with nonthyroidal disease. J Clin Endocrinol Metab. 1995;80:971–6.

    Article  PubMed  CAS  Google Scholar 

  52. Kumara-Siri MH, Lee K, Surks MI. Regulation of thyrotropin secretion in rats bearing the Walker 256 carcinoma. Endocrinology. 1981;109:1760–8.

    Article  PubMed  CAS  Google Scholar 

  53. Hupart KH, Defesi CR, Katz CP, Shapiro LE, Surks MI. Decreased anterior pituitary T3 nuclear receptors in a Walker 256 carcinoma-bearing rat model of nonthyroidal disease. Acta Endocrinol (Copenh). 1989; 121:811–6.

    CAS  Google Scholar 

  54. WHO/ICCIDD/UNICEF. Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. 3rd ed. Geneva: World Health Organization; 2007.

    Google Scholar 

  55. Gardner DF, Kaplan MM, Stanley CA, Utiger RD. Effect of tri-iodothyronine replacement of the metabolic and pituitary responses to starvation. N Engl J Med. 1979;300:579–84.

    Article  PubMed  CAS  Google Scholar 

  56. Dillmann WH, Berry S, Alexander NM. A physiological does of triiodothyronine normalizes cardiac myosin adenosine triphosphatase activity and changes myosin isoenzyme distribution in semistarved rats. Endocrinology. 1983;112:2081–7.

    Article  PubMed  CAS  Google Scholar 

  57. Katzeff HL, Powell SR, Ojamaa K. Alterations in cardiac contractility and gene expression during low-T3 syndrome: prevention with T3. Am J Physiol. 1997;273:951–6.

    Google Scholar 

  58. Tibaldi JM, Surks MI. Animal models of nonthyroidal disease. Endocr Rev. 1985;6:87–102.

    Article  PubMed  CAS  Google Scholar 

  59. Shapiro LE, Wasserman SH, Katz CP, Surks MI. 3,5,3′-triiodothyronine determines the viability of GC Cells after heat shock. Endocrinology. 1989;124: 1026–32.

    Article  PubMed  CAS  Google Scholar 

  60. Shapiro LE, Katz CP, Defesi CR, Surks MI. Heat shock of cultured GC cells enhances the level of triiodothyronine induced growth hormone (GH) and GH messenger ribonucleic acid. Endocrinology. 1989;125:180–5.

    Article  PubMed  CAS  Google Scholar 

  61. Feder ME. Heat shock proteins, molecular chaperones and the stress response: evolutionary and ecological physiology. Annu Rev Physiol. 1999;61:243–82.

    Article  PubMed  CAS  Google Scholar 

  62. Mokshagundam S, Shapiro LE, Surks MI. Heat stress of cultured GC cells enhances triiodothyronine-induced growth hormone production by action within the 5′-flanking region of the rat growth hormone gene. Biochem Biophys Res Commun. 1992;188:638–43.

    Article  PubMed  CAS  Google Scholar 

  63. Bruck R, Frenkel D, Shirin H, et al. Hypothyroidism protects rat liver from acetaminophen hepatotoxicity. Dig Dis Sci. 1999;44:1228–35.

    Article  PubMed  CAS  Google Scholar 

  64. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007;116:1725–35.

    Article  PubMed  Google Scholar 

  65. Danzi S, Klein I. Thyroid hormone-regulated cardiac gene expression and cardiovascular disease. Thyroid. 2002;12:467–72.

    Article  PubMed  CAS  Google Scholar 

  66. Dillmann WH. Hormonal influences on cardiac myosin ATPase activity and myosin isoenzyme distribution. Mol Cell Endocrinol. 1984;34:169–18.

    Article  PubMed  CAS  Google Scholar 

  67. Portman MA. Thyroid economy-regulation, cell biology, thyroid hormone metabolism and action: the special edition: metabolic effects of thyroid hormones. Thyroid. 2008;18:167–74.

    Article  Google Scholar 

  68. Henderson KK, Danzi S, Paul JT, Leya G, Klein I, Samarel AM. Physiological replacement of T3 improves left ventricular function in an animal model of myocardial infarction-induced congestive heart failure. Circ Heart Fail. 2009;2:243–52.

    Article  PubMed  Google Scholar 

  69. Blake NG, Eckland DJ, Foster OJ, Lightman SL. Inhibition of hypothalamic thyrotropin-releasing hormone messenger ribonucleic acid during food deprivation. Endocrinology. 1991;129:2714–8.

    Article  PubMed  CAS  Google Scholar 

  70. Van den Berghe G, de Zegher P, Baxter RC, et al. Neuroendocrinology of prolonged critical illness: effects of exogenous thyrotropin-releasing hormone and its combination with growth hormone secretagogues. JCEM. 1998;83:309–19.

    PubMed  Google Scholar 

  71. Becker RA, Vaughan GM, Siegler MG, et al. Hypermetabolic low triiodithyroinine syndrome of burn injury. Crit Care Med. 1982;10:870–5.

    Article  PubMed  CAS  Google Scholar 

  72. Acker CG, et al. A trial of thyroxine in acute renal failure. Kidney Int. 2000;57:293–8.

    Article  PubMed  CAS  Google Scholar 

  73. Acker CG. Thyroid hormone in the treatment of post-transplant acute tubular necrosis (ATN). Am J Transplant. 2002;2:57–61.

    Article  PubMed  CAS  Google Scholar 

  74. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344:501–9.

    Article  PubMed  CAS  Google Scholar 

  75. Iervasi G, et al. Low T-3 Syndrome: a strong prognostic predictor of death in patients with heart disease. Circulation. 2003;107:708–13.

    Article  PubMed  Google Scholar 

  76. Moruzzi P, et al. Medium-term effectiveness of L-thyroxine treatment in idiopathic dilated cardiomyopthay. Am J Med. 1996;101:461–7.

    Article  PubMed  CAS  Google Scholar 

  77. Hamilton MA, et al. Safety and hemodunamic effects of intravenous triiodothyronine in advanced congestive heart failure. Am J Cardiol. 1998;81:443–7.

    Article  PubMed  CAS  Google Scholar 

  78. Pingitore A, et al. Acute effects of triiodothyronine (T3) replacement therapy in patients with chronic heart failure and low-T3 syndrome: a randomized, placebo-controlled study. J Clin Endocrinol Metab. 2008;93:1351–8.

    Article  PubMed  CAS  Google Scholar 

  79. Novitsky D, Human PA, Cooper DKC. Effect of triiodothyronine (T3) on myocardial high energy phosphates and lactate following ischemia and cardiopulmonary bypass. An experimental study in baboons. J Thorac Cardiovasc Surg. 1988;96:600–7.

    Google Scholar 

  80. Novitzky D, et al. Triiodothyronine in the recovery of stunned myocardium in dogs. Ann Thorac Surg. 1991;51:10–7.

    Article  PubMed  CAS  Google Scholar 

  81. Novitzky D, et al. Inotropic effect of triiodothronine following myocardial ischemia and cardiopulmonary bypass and experimental study in pigs. Ann Thorac Surg. 1998;45:50–5.

    Article  Google Scholar 

  82. Kaptein EM, et al. Thyroid hormone therapy for postoperative nonthyroidal illness: a systematic review and synthesis. J Clin Endocrinol Metab. 2010;95:4526–34.

    Article  PubMed  CAS  Google Scholar 

  83. Novitzky D. Novel action of thyroid hormone: the role of triiodothyronine in cardiac transplantation. Thyroid. 1996;6:531–6.

    Article  PubMed  CAS  Google Scholar 

  84. Jeevanandam V. Triiodothyronine: spectrum of use in heart transplantation. Thyroid. 1997;7:139–45.

    Article  PubMed  CAS  Google Scholar 

  85. Salim A, Vassiliu P, Velmahos GC, et al. The role of thyroid hormone administration in potential organ donors. Arch Surg. 2001;136:1377–80.

    Article  PubMed  CAS  Google Scholar 

  86. Salim A, Brown MM, Inaba L, et al. Using thyroid hormone in brain-dead donors to maximize the number of organs available for transplantation. Clin Transplant. 2007;21:405–9.

    Article  PubMed  Google Scholar 

  87. Zaroff JG, Rosengard BR, Armstrong WF, et al. Consensus conference report: maximizing use of organs recovered from the cadaver donor: cardiac recommendations. March 28–29 2001, Cristal City VA. Circulation. 2002;106:836–41.

    Article  PubMed  Google Scholar 

  88. Novitzky D, Cooper DKC, Chaffin JS, Greer AE, De Bault LE, Zuhdi N. Improved cardiac allograft function following Triiodothyronine therapy to both donor and recipient. Transplantation. 1990;49:311–6.

    Article  PubMed  CAS  Google Scholar 

  89. Schmidt BM, Martin N, Georgen AC, et al. Nongenomic cardiovascular effects of triiodothyronine in euthyroid male volunteers. J Clin Endocrinol Metab. 2002;87:1681–6.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

We are grateful to Ms. Kara Ghaney for assistance in the preparation of this chapter.

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Correspondence to Lawrence E. Shapiro M.D. .

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Shapiro, L.E., Baron, T. (2013). The Efficacy of Thyroid Hormone Therapy in Brain-Dead Heart Donors: A Review of Thyroid Function in Health and Disease. In: Novitzky, D., Cooper, D. (eds) The Brain-Dead Organ Donor. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4304-9_8

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