Thyroid Hormone Treatment in Acute Myocardial Infarction

  • Salman RazviEmail author


Circulating as well as tissue thyroid hormone levels are reduced after an acute myocardial infarction (AMI) and this phenomenon is associated with worse outcomes. It is unclear whether the changes in thyroid hormone bio-availability to the affected myocardium is an adaptive response or if this is a dysfunctional reaction. Experimental studies from animal models of AMI suggest that thyroid hormone treatment in the AMI setting may be beneficial. However, data from clinical trials of thyroid hormone treatment in AMI is rather limited. Large-scale clinical trials of thyroid hormones in patients with AMI and thyroid dysfunction are required to evaluate which hormone to administer (thyroxine or triiodothyronine), when to treat (early to reduce ischaemia-reperfusion injury or later to help modulate myocardial remodelling), how much thyroid hormone to dispense (to normalise thyroid hormone concentrations or to increase levels just above the reference range), and which parameters to utilise to assess safety and efficacy. Until these important questions are answered thyroid hormone therapy in AMI must remain within the research realm.


Thyroid hormones Acute myocardial infarction Thyroxine Triiodothyronine Left ventricular function 


  1. 1.
    Hartley A, Marshall DC, Salciccioli JD, Sikkel MB, Maruthappu M, Shalhoub J. Trends in mortality from ischemic heart disease and cerebrovascular disease in Europe: 1980 to 200. Circulation. 2016;133(20):1916–26.PubMedCrossRefGoogle Scholar
  2. 2.
    Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119–77.CrossRefGoogle Scholar
  3. 3.
    Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest. 2013;123:92–100.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Razvi S, Jabbar A, Pingitore A, Danzi S, Biondi B, Klein I, Peeters R, Zaman A, Iervasi G. Thyroid hormones and cardiovascular function and diseases. J Am Coll Cardiol. 2018;71:1781–96.PubMedCrossRefGoogle Scholar
  5. 5.
    Pingitore A, Nicolinin G, Kusmic C, Iervasi G, Grigolini P, Forinin F. Cardioprotection and thyroid hormones. Heart Fail Rev. 2016;21:391–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Pol CJ, Muller A, Zuidwijk MJ, van Deel ED, Kaptein E, Saba A, Marchini M, Zucchi R, Visser TJ, Paulus WJ, Duncker DJ, Simonides WS. Left-ventricular remodelling after myocardial infarction is associated with a cardiomyocyte-specific hypothyroid condition. Endocrinology. 2011;152:669–79.PubMedCrossRefGoogle Scholar
  7. 7.
    Song Y, Li J, Bian S, Qin J, Song Y, Jin J, Zhao X, Song M, Chen J, Huang L. Association between low free triiodothyronine levels and poor prognosis in patients with acute ST-elevation myocardial infarction. Biomed Res Int. 2018;2018:9803851.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Iervasi G, Pingitore A, Landi P, Raciti M, Ripoli A, Scarlattini M, L’Abbate A, Donato L. Low-T3 syndrome: a prognostic predictor of death in patients with heart disease. Circulation. 2003;107:708–13.PubMedCrossRefGoogle Scholar
  9. 9.
    Jabbar A, Pingitore A, Pearce SH, Zaman A, Iervasi G, Razvi S. Thyroid hormones and cardiovascular disease. Nat Rev Cardiol. 2017;14:39–55.PubMedCrossRefGoogle Scholar
  10. 10.
    Rajagopalan V, Zhang Y, Pol C, Costello C, Seitter S, Lehto A, Savinova OV, Chen YF, Gerdes AM. Modified low-dose triiodo-L-thyronine therapy safely improves function following myocardial ischemia-reperfusion injury. Front Physiol. 2017;8:225.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    Files MD, Kajimoto M, O’Kelly Priddy CM, Ledee DR, Xu C, Des Rosiers C, Isern N, Portman MA. Triiodothyronine facilitates weaning from extracorporeal membrane oxygenation by improved mitochondrial substrate utilization. J Am Heart Assoc. 2014;3:e000680.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Lesmana R, Sinha RA, Singh BK, Zhou J, Ohba K, Wu Y, Yau WW, Bay BH, Yen PM. Thyroid hormone stimulation of autophagy is essential for mitochondrial biogenesis and activity in skeletal muscle. Endocrinology. 2016;157:23–38.PubMedCrossRefGoogle Scholar
  14. 14.
    Yehuda-Shnaidman E, Kalderon B, Azazmeh N, Bar-Tana J. Gating of the mitochondrial permeability transition pore by thyroid hormone. FASEB J. 2010;24:93–104.PubMedCrossRefGoogle Scholar
  15. 15.
    Simonides WS, Mulcahey MA, Redout EM, Muller A, Zuidwijk MJ, Visser TJ, Wassen FW, Crescenzi A, da-Silva WS, Harney J, Engel FB, Obregon MJ, Larsen PR, Bianco AC, Huang SA. Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats. J Clin Invest. 2008;118:975–83.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Weltman NY, Ojamaa K, Schlenker EH, Chen YF, Zucchi R, Saba A, Colligiani D, Rajagopalan V, Pol CJ, Gerdes AM. Low-dose T3 replacement restores depressed cardiac T3 levels, preserves coronary microvasculature and attenuates cardiac dusfunction in experimental diabetes mellitus. Mol Med. 2014;20:302–12.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Pantos C, Mourouzis I, Saranteas T, Clave G, Ligeret H, Noack-Fraissignes P, Renard PY, Massonneau M, Perimenis P, Spanou D, Kostopanagiotou G, Cokkinos DV. Thyroid hormone improves postischaemic recovery of function while limiting apoptosis: a new therapeutic approach to support hemodynamics in the setting of ischaemia-reperfusion? Basic Res Cardiol. 2009;104:69–77.PubMedCrossRefGoogle Scholar
  18. 18.
    Ojamaa K, Kenessey A, Shenoy R, Klein I. Thyroid hormone metabolism and cardiac gene expression after acute myocardial infarction in the rat. Am J Physiol Endocrinol Metab. 2000;279:E1319–24.PubMedCrossRefGoogle Scholar
  19. 19.
    Pantos C, Mourouzis I, Markakis K, Dimopoulos A, Xinaris C, Kokkinos AD, Panagiotou M, Cokkinos DV. Thyroid hormone attenuates cardiac remodeling and improves hemodynamics early after acute myocardial infarction in rats. Eur J Cardiothorac Surg. 2007;32:333–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Friberg L, Drvota V, Bjelak AH, Eggertsen G, Ahnve S. Association between increased levels of reverse triiodothyronine and mortality after acute myocardial infarction. Am J Med. 2001;111:699–703.PubMedCrossRefGoogle Scholar
  21. 21.
    Pavlou HN, Kliridis PA, Panagiotopoulos AA, Goritsas CP, Vassilakos PJ. Euthyroid sick syndrome in acute ischemic syndromes. Angiology. 2002;53:699–707.PubMedCrossRefGoogle Scholar
  22. 22.
    Friberg L, Werner S, Eggertsen G, Ahnve S. Rapid down-regulation of thyroid hormones in acute myocardial infarction: is it cardioprotective in patients with angina? Arch Intern Med. 2002;162:1388–94.PubMedCrossRefGoogle Scholar
  23. 23.
    Iltumur K, Olmez G, Ariturk Z, Taskesen T, Toprak N. Clinical investigation: thyroid function test abnormalities in cardiac arrest associated with acute coronary syndrome. Crit Care. 2005;9:R416–24.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Pimental RC, Cardoso GP, Escosteguy CC, Abreu LM. Thyroid hormone profile in acute coronary syndromes. Arq Bras Cardiol. 2006;87:688–94.Google Scholar
  25. 25.
    Adawiyah J, Norasyikin AW, Mat NH, Shamsul AS, Azmi KN. The non-thyroidal illness syndrome in acute coronary syndrome is associated with increased cardiac morbidity and mortality. Heart Asia. 2010;6:11–4.CrossRefGoogle Scholar
  26. 26.
    Lymvaios I, Mourouzis I, Cokkinos DV, Dimopoulos MA, Toumanidis ST, Pantos C. Thyroid hormone and recovery of cardiac function in patients with acute myocardial infarction: a strong association? Eur J Endocrinol. 2011;165:107–14.PubMedCrossRefGoogle Scholar
  27. 27.
    Zhang B, Peng W, Wang C, Li W, Xu Y. A low fT3 levels as a prognostic marker in patients with acute myocardial infarctions. Intern Med. 2012;51:3009–15.PubMedCrossRefGoogle Scholar
  28. 28.
    Lazzeri C, Sori A, Picariello C, Chiostri M, Gensini GF, Valente S. Nonthyroidal illness syndrome in ST-elevation myocardial infarction treated with mechanical revascularisation. Int J Cardiol. 2012;158:103–4.PubMedCrossRefGoogle Scholar
  29. 29.
    Ozcan KS, Osmonov D, Toprak E, Gungor B, Tatlisu A, Ekmekci A, Kaya A, Tayyareci G, Erdinler I. Sick euthyroid syndrome is associated with poor prognosis in patients with ST segment elevation myocardial infarction undergoing primary percutaneous intervention. Cardiol J. 2014;21:238–44.PubMedCrossRefGoogle Scholar
  30. 30.
    Kim DH, Choi DH, Kim HW, Choi SW, Kim BB, Chung JW, Koh YY, Chang KS, Hong SP. Prediction of infarct severity from triiodothyronine levels in patients with ST-elevation myocardial infarction. Korean J Intern Med. 2014;29:454–65.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Abdulaziz Qari F. Thyroid hormone profile in patients with acute coronary syndrome. Iran Red Crescent Med J. 2015;17:e26919.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Yazici S, Kiris T, Ceylan US, Terzi S, Erdem A, Atasoy I, Emre A, Yesilcimen K. Relation of low T3 to one-year mortality in non-ST-elevation acute coronary syndrome patients. J Clin Lab Anal. 2017;31:e22036. Scholar
  33. 33.
    Brozaitiene J, Mickuviene N, Pdlipskyte A, Burkauskas J, Bunevicius R. Relationship and prognostic importance of thyroid hormone and N-terminal pro-B-type natriuretic peptide for patients after acute coronary syndromes: a longitudinal observational study. BMC Cardiovasc Disord. 2016;16:45.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Tu T, Tian C, Song J, He D, Wu J, Wen Z, Sun Z, Sun Z. Value of the fT3/fT4 ratio and its combination with the GRACE risk score in predicting the prognosis in euthyroid patients with acute myocardial infarction undergoing percutaneous coronary intervention: a prospective cohort study. BMC Cardiovasc Disord. 2018;18:181.CrossRefGoogle Scholar
  35. 35.
    Pingitore A, Mastorci F, Piaggi P, Aquaro GD, Molinaro S, Ravani M, De Caterina A, Trianni G, Ndreu R, Beri S, Vassalle C, Iervasi G. Usefulness of triiodothyronine replacement therapy in patients with ST elevation myocardial infarction and borderline/reduced triiodothyronine levels (from the THIRST study). Am J Cardiol. 2019;123:905–12.PubMedCrossRefGoogle Scholar
  36. 36.
    Ranasinghe AM, Quinn DW, Pagano D, Edwards N, Faroqui M, Graham TR, Keogh BE, Mascaro J, Riddington DW, Rooney SJ, Townend JN, Wilson IC, Bonser RS. Glucose-insulin-potassium and tri-iodothyronine individually improve hemodynamic performance and are associated with reduced troponin I release after on-pump coronary artery bypass grafting. Circulation. 2006;114:I245–50.PubMedGoogle Scholar
  37. 37.
    Zhang JQ, Yang QY, Xue FS, Zhang W, Yang GZ, Liao X, Meng FM. Preoperative oral thyroid hormones to prevent euthyroid sick syndrome and attenuate myocardial ischemia-reperfusion injury after cardiac surgery with cardiopulmonary bypass in children: a randomized, double-blind, placebo-controlled trial. Medicine (Baltimore). 2018;97:e12100.PubMedCentralCrossRefPubMedGoogle Scholar
  38. 38.
    Portman MA, Slee A, Olson AK, Cohen G, Karl T, Tong E, Hastings L, Patel H, Reinhartz O, Mott AR, Mainwaring R, Linam J, Danzi S, TRICC Investigators. Triiodothyronine supplementation in infants and children undergoing cardiopulmonary bypass (TRICC): a multicenter placebo-controlled randomized trial: age analysis. Circulation. 2010;122:S224–33.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Novitzky D, Mi Z, Sun Q, Collins JF, Cooper DK. Thyroid hormone therapy in the management of 63,593 brain-dead organ donors: a retrospective analysis. Transplantation. 2014;98:1119–27.PubMedCrossRefGoogle Scholar
  40. 40.
    Cooper LB, Milano CA, Williams M, Swafford W, Croezen D, Van Bakel AB, Rogers JG, Patel CB. Thyroid hormone use during cardiac transplant organ procurement. Clin Transpl. 2016;30:1578–83.CrossRefGoogle Scholar
  41. 41.
    Zaroff JG, Rosengard BR, Armstrong WF, Babcock WD, D’Alessandro A, Dec GW, Edwards NM, Higgins RS, Jeevanandum V, Kauffman M, Kirklin JK, Large SR, Marelli D, Peterson TS, Ring WS, Robbins RC, Russell SD, Taylor DO, Van Bakel A, Wallwork J, Young JB. Consensus conference report: maximizing use of organs recovered from the cadaver donor: cardiac recommendations, March 28-29, 2001, Crystal City, Va. Circulation. 2002;106:836–41.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Stamler J. The coronary drug project—findings with regard to estrogen, dextrothyroxine, clofibrate and niacin. Adv Exp Med Biol. 1977;82:52–75.PubMedGoogle Scholar
  43. 43.
    Young WF Jr, Gorman CA, Jiang NS, Machacek D, Hay ID. L-thyroxine contamination of pharmaceutical D-thyroxine: probable cause of therapeutic effect. Clin Pharmacol Ther. 1984;36:781–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Pennock GD, Raya TE, Bahl JJ, Goldman S, Morkin E. Cardiac effects of 3,5-diiodothyropropionic acid, a thyroid hormone analog with inotropic selectivity. J Pharmacol Exp Ther. 1992;263:163–9.PubMedGoogle Scholar
  45. 45.
    Wang X, Zheng W, Christensen LP, Tomanek RJ. DITPA stimulates bFGF, VEGF, angiopoietin, and Tie-2 and facilitates coronary arteriolar growth. Am J Physiol Heart Circ Physiol. 2003;284:H613–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Morkin E, Pennock G, Spooner PH, Bahl JJ, Underhill Fox K, Goldman S. Pilot studies on the use of 3,5-diiodothyropropionic acid, a thyroid hormone analog, in the treatment of congestive heart failure. Cardiology. 2002;97:218–25.PubMedCrossRefGoogle Scholar
  47. 47.
    Goldman S, McCarren M, Morkin E, Ladenson PW, Edson R, Warren S, Ohm J, Thai H, Churby L, Barnhill J, O’Brien T, Anand I, Warner A, Hattler B, Dunlap M, Erikson J, Shih MC, Lavori P. DITPA (3,5-diiodothyropropionic acid), a thyroid hormone analog to treat heart failure: phase II trial veterans affairs cooperative study. Circulation. 2009;119:3093–100.PubMedCrossRefGoogle Scholar
  48. 48.
    Chen YF, Weltman NY, Li X, Youman S, Krause D, Gerdes AM. Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats. J Transl Med. 2013;11:40.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Jabbar A, Ingoe L, Pearce SH, Zaman A, Razvi S. Thyroxine in acute myocardial infarction (ThyrAMI)—levothyroxine in subclinical hypothyroidism post-acute myocardial infarction: study protocol for a randomised controlled trial. Trials. 2015;16:115.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Vidart J, Wajner SM, Leite RS, Manica A, Schaan BD, Larsen PR, Maia AL. N-acetylcysteine administration prevents nonthyroidal illness syndrome in patients with acute myocardial infarction: a randomized clinical trial. J Clin Endocrinol Metab. 2014;99:4537–45.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Tribulova N, Knezi V, Shainberg A, Seki S, Soukup T. Thyroid hormones and cardiac arrhythmias. Vascul Pharmacol. 2010;52:102–12.PubMedCrossRefGoogle Scholar
  52. 52.
    Utiger RD. Altered thyroid function in nonthyroidal illness and surgery. To treat or not to treat? N Engl J Med. 1995;333:1562–3.PubMedCrossRefGoogle Scholar
  53. 53.
    Pantos C, Mourouzis I, Tsagoulis N, Markakis K, Galanopoulos G, Roukounakis N, Perimenis P, Liappas A, Cokkinos DV. Thyroid hormone at supra-physiological dose optimizes cardiac geometry and improves cardiac function in rats with old myocardial infarction. J Physiol Pharmacol. 2009;60:49–56.PubMedGoogle Scholar
  54. 54.
    Rajagopalan V, Zhang Y, Ojamaa K, Chen YF, Pingitore A, Pol CJ, Saunders D, Balasubramaniam K, Towner RA, Gerdes AM. Safe oral triiodo-L-thyronine therapy protects from post-infarct cardiac dysfunction and arrhythmias without cardiovascular adverse effects. PLoS One. 2016;11:e0151413.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Zhang K, Tang YD, Zhang Y, Ojamaa K, Li Y, Saini AS, Carrillo-Sepulveda MA, Rajagopalan V, Gerdes AM. Comparison of therapeutic triiodothyronine versus metoprolol in the treatment of myocardial infarction in rats. Thyroid. 2018;28:799–810.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Liu Y, Redetzke RA, Said S, Pottala JV, de Escobar GM, Gerdes AM. Serum thyroid hormone levels may not accurately reflect thyroid tissue levels and cardiac function in mild hypothyroidism. Am J Physiol Heart Circ Physiol. 2008;294:H2137–43.PubMedCrossRefGoogle Scholar
  57. 57.
    Peeters RP, Wouters PJ, van Toor H, Kaptein E, Visser TJ, Van den Berghe G. Serum rT3 and T3/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.PubMedCrossRefGoogle Scholar
  58. 58.
    De K, Ghosh G, Datta M, Konar A, Bandyopadhyay J, Bandyopadhyay D, Bhattacharya S. Analysis of differentially expressed genes in hyperthyroid-induced hypertrophied heart by cDNA microarray. J Endocrinol. 2004;182:303–14.PubMedCrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Institute of Clinical and Translational Medicine, Newcastle University/Queen Elizabeth HospitalNewcastle upon TyneUK

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