Heart in Hypothyroidism

  • Bernadette BiondiEmail author
  • George J. Kahaly


The transition from the fetal to the adult phenotype heart depends on the increase in thyroid hormone (TH) in perinatal period (Liu and Gerdes, J Mol Cell Cardiol 22:1339–1348, 1990; Gerdes and Iervasi, Circulation 122:385–393, 2010). Moreover, T3 action is essential for preserving both cardiac morphology and performance in adult life because thyroid hormone controls the inotropic and lusitropic properties of the myocardium, cardiac growth, myocardial contractility, and vascular function (Liu and Gerdes, J Mol Cell Cardiol 22:1339–1348, 1990; Gerdes and Iervasi, Circulation 122:385–393, 2010; Fazio et al., Recent Prog Horm Res 59:31–50, 2002; Kahaly and Dillmann, Endocr Rev 26:704–728, 2005; Klein and Ojamaa, N Engl J Med 344:501–509, 2001; Biondi and Klein, Endocrine 24:1–13, 2004). Most patients with thyroid dysfunction experience cardiovascular (CV) manifestations, and the most serious complications of thyroid disease occur as a result of cardiac involvement (Fazio et al., Recent Prog Horm Res 59:31–50, 2002; Kahaly and Dillmann, Endocr Rev 26:704–728, 2005; Klein and Ojamaa, N Engl J Med 344:501–509, 2001; Biondi and Klein, Endocrine 24:1–13, 2004). Severe hypothyroidism or myxedema has a clinically relevant impact on the heart and on the cardiovascular system, and measurable changes in cardiovascular performance are detected even with small variations in thyroid hormone concentrations (Liu and Gerdes, J Mol Cell Cardiol 22:1339–1348, 1990; Gerdes and Iervasi, Circulation 122:385–393, 2010; Fazio et al., Recent Prog Horm Res 59:31–50, 2002; Kahaly and Dillmann, Endocr Rev 26:704–728, 2005; Klein and Ojamaa, N Engl J Med 344:501–509, 2001; Biondi and Klein, Endocrine 24:1–13, 2004).

Here we explore the hemodynamic alterations in overt and subclinical hypothyroidism (SHypo), their cardiovascular risks, the prevention and treatment of these disorders, and their cardiovascular complications.


Subclinical hypothyroidism Overt hypothyroidism Cardiovascular risk Management l-thyroxine 


  1. 1.
    Liu Z, Gerdes AM. Influence of hypothyroidism and the reversal of hypothyroidism on hemodynamics and cell size in the adult rat heart. J Mol Cell Cardiol. 1990;22:1339–48.CrossRefGoogle Scholar
  2. 2.
    Gerdes AM, Iervasi G. Thyroid replacement therapy and heart failure. Circulation. 2010;122:385–93.CrossRefGoogle Scholar
  3. 3.
    Fazio S, Palmieri EA, Lombardi G, Biondi B. Effects of thyroid hormone on the cardiovascular system. Recent Prog Horm Res. 2002;59:31–50.CrossRefGoogle Scholar
  4. 4.
    Kahaly GJ, Dillmann WH. Thyroid hormone action in the heart. Endocr Rev. 2005;26:704–28.CrossRefGoogle Scholar
  5. 5.
    Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344:501–9.CrossRefGoogle Scholar
  6. 6.
    Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine. 2004;24:1–13.CrossRefGoogle Scholar
  7. 7.
    Buccino RA, Spann JF Jr, Pool PE, Sonnenblick EH, Braunwald E. Influence of the thyroid state on the intrinsic contractile properties and energy stores of the myocardium. J Clin Invest. 1967;46:1669–82.CrossRefGoogle Scholar
  8. 8.
    Crowley WF Jr, Ridgway EC, Bough EW, Francis GS, Daniels GH, Kourides IA, Myers GS, Maloof F. Noninvasive evaluation of cardiac function in hypothyroidism. Response to gradual thyroxine replacement. N Engl J Med. 1977;296:1–6.CrossRefGoogle Scholar
  9. 9.
    Manns JJ, Shepherd AMM, J Crooks DG. Adamson measurement of cardiac muscle relaxation in hypothyroidism. Br Med J. 1976;1:1366–8.CrossRefGoogle Scholar
  10. 10.
    Santos AD, Miller RP, Mathew PK, Wallance WA, Cave WT, Hinojosa L. Echocardiographic characterization of the reversible cardiomyopathy of hypothyroidism. Am J Med. 1980;68:675–82.CrossRefGoogle Scholar
  11. 11.
    Galderisi M, Vitale G, D’Errico A, Lupoli GA, Ciccarelli A, Cicala S, Pardo M, Lupoli G, de Divitiis O. Usefulness of pulsed tissue Doppler for the assessment of left ventricular myocardial function in overt hypothyroidism. Ital Heart. 2004;5:257–64.Google Scholar
  12. 12.
    Tielens E, Pillary M, Storm C, Berghout A. Changes in cardiac function at rest before and after treatment in primary hypothyroidism. Am J Cardiol. 2000;85:376–80.CrossRefGoogle Scholar
  13. 13.
    Virtanen VK, Saha HH, Groundstroem KW, Salmi J, Pasternack AI. Thyroid hormone substitution therapy rapidly enhances left-ventricular diastolic function in hypothyroid patients. Cardiology. 2001;96:59–64.CrossRefGoogle Scholar
  14. 14.
    Kahaly GJ, Kampmann C, Mohr-Kahaly S. Cardiovascular hemodynamics and exercise tolerance in thyroid disease. Thyroid. 2002;12:473–81.CrossRefGoogle Scholar
  15. 15.
    Dernellis J, Panaretou M. Effects of thyroid replacement therapy on arterial blood pressure in patients with hypertension and hypothyroidism. Am Heart J. 2002;143:718–24.CrossRefGoogle Scholar
  16. 16.
    Saito I, Ito K, Saruta T. Hypothyroidism as a cause of hypertension. Hypertension. 1983;5:112–5.CrossRefGoogle Scholar
  17. 17.
    Fommei E, Iervasi G. The role of thyroid hormone in blood pressure homeostasis: evidence from short-term hypothyroidism in humans. J Clin Endocrinol Metab. 2002;87:1996–2000.CrossRefGoogle Scholar
  18. 18.
    Bengel FM, Nekolla SG, Ibrahim T, Weniger C, Ziegler SI, Schwaiger M. Effect of thyroid hormones on cardiac function, geometry, and oxidative metabolism assessed noninvasively by positron emission tomography and magnetic resonance imaging. J Clin Endocrinol Metab. 2000;85:1822–7.CrossRefGoogle Scholar
  19. 19.
    Iglesias P, Díez JJ. Thyroid dysfunction and kidney disease. Eur J Endocrinol. 2009;160:503–15.CrossRefGoogle Scholar
  20. 20.
    Kinne R, De Santo NG. Effects of thyroid hormones on heart and kidney functions. Miner Electrolyte Metab. 1999;25:56–64.CrossRefGoogle Scholar
  21. 21.
    Montenegro J, Gonzalez O, Saracho R, Aguirre R, Gonzalez O, Martinez I. Changes in renal function in primary hypothyroidism. Am J Kidney Dis. 1996;27:195–8.CrossRefGoogle Scholar
  22. 22.
    Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab. 2003;88:2438–44.CrossRefGoogle Scholar
  23. 23.
    Duntas LH. Thyroid disease and lipids. Thyroid. 2002;12:287–93.CrossRefGoogle Scholar
  24. 24.
    Biondi B, Palmieri EA, Lombardi G, Fazio S. Subclinical hypothyroidism and cardiac function. Thyroid. 2002;12:505–10.CrossRefGoogle Scholar
  25. 25.
    Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Ann Intern Med. 2002;137:904–14.CrossRefGoogle Scholar
  26. 26.
    Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29:76–131.CrossRefGoogle Scholar
  27. 27.
    Biondi B, Cooper DS. Subclinical thyroid disease. Lancet. 2012;379:1142–54.CrossRefGoogle Scholar
  28. 28.
    Biondi B. Cardiovascular effects of mild hypothyroidism. Thyroid. 2007;17:625–30.CrossRefGoogle Scholar
  29. 29.
    Biondi B, Fazio S, Palmieri EA, Carella C, Panza N, Cittadini A, Bonè F, Lombardi G, Saccà L. Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism. J Clin Endocrinol Metab. 1999;84:2064–7.CrossRefGoogle Scholar
  30. 30.
    Mohr-Kahaly S, Beyer J, Meyer J. Left ventricular function analyzed by Doppler and echocardiographic methods in short-term hypothyroidism. Am J Cardiol. 1995;75:645–8.CrossRefGoogle Scholar
  31. 31.
    Vitale G, Galderisi M, Lupoli GA, Celentano A, Pietropaolo I, Parenti N, de Divitis O, Lupoli G. Left ventricular myocardial impairment in subclinical hypothyroidism assessed by a new ultrasound tool: pulsed tissue Doppler. J Clin Endocrinol Metab. 2002;87:4350–5.CrossRefGoogle Scholar
  32. 32.
    Ripoli A, Pingitore A, Favilli B, Bottoni A, Turchi S, Osman NF, De Marchi D, Lombardi M, L’Abbate A, Iervasi G. Does subclinical hypothyroidism affect cardiac pump performance? Evidence from a magnetic resonance imaging study. J Am Coll Cardiol. 2005;45:439–45.CrossRefGoogle Scholar
  33. 33.
    Brenta G, Mutti LA, Schnitman M, Fretes O, Perrone A, Matute ML. Assessment of left ventricular diastolic function by radionuclide ventriculography at rest and exercise in subclinical hypothyroidism, and its response to L-thyroxine therapy. Am J Cardiol. 2003;91:1327–30.CrossRefGoogle Scholar
  34. 34.
    Owen PJD, Rajiv C, Vinereanu D, Mathew T, Fraser AG, Lazarus JH. Subclinical hypothyroidism, arterial stiffness and myocardial reserve. J Clin Endocrinol Metab. 2006;9:2126–32.CrossRefGoogle Scholar
  35. 35.
    Nagasaki T, Inaba M, Kumeda Y, Hiura Y, Shirakawa K, Yamada S, Henmi Y, Ishimura E, Nishizawa Y. Increased pulse wave velocity in subclinical hypothyroidism. J Clin Endocrinol Metab. 2006;91:154–8.CrossRefGoogle Scholar
  36. 36.
    Biondi B, Galderisi M, Pagano L, Sidiropulos M, Pulcrano M, D’Errico A, Ippolito S, Rossi A, de Divitiis O, Lombardi G. Endothelial-mediated coronary flow reserve in patients with mild thyroid hormone deficiency. Eur J Endocrinol. 2009;161:323–9.CrossRefGoogle Scholar
  37. 37.
    Lekakis J, Papamichael C, Alevizaki M, Piperingos G, Marafelia P, Mantzos J, Stamatelopoulos S, Koutras DA. Flow-mediated, endothelium-dependent vasodilation is impaired in subjects with hypothyroidism, borderline hypothyroidism, and high-normal serum thyrotropin (TSH) values. Thyroid. 1997;7:411–4.CrossRefGoogle Scholar
  38. 38.
    Danese MD, Ladenson PW, Meinert CL, Powe NR. Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J Clin Endocrinol Metab. 2000;85:2993–3001.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Bakker SJ, ter Maaten JC, Popp-Snijders C, Slaets JP, Heine RJ, Gans RO. The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects. J Clin Endocrinol Metab. 2001;86:1206–11.PubMedGoogle Scholar
  40. 40.
    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.CrossRefGoogle Scholar
  41. 41.
    Tang YD, Kuzman JA, Said S, Anderson BE, Wang X, Gerdes AM. Low thyroid function leads to cardiac atrophy with chamber dilatation, impaired myocardial blood flow, loss of arterioles, and severe systolic dysfunction. Circulation. 2005;112:3122–30.CrossRefGoogle Scholar
  42. 42.
    Ladenson PW, Sherman SI, Baughman KL, Ray PE, Feldman AM. Reversible alterations in myocardial gene expression in a young man with dilated cardiomyopathy and hypothyroidism. Proc Natl Aca Sci USA. 1992;89:5251–5.CrossRefGoogle Scholar
  43. 43.
    Biondi B. Heart failure and thyroid dysfunction. Eur J Endocrinol. 2012;167:609–18.CrossRefGoogle Scholar
  44. 44.
    Rodondi N, Bauer DC, Cappola AR, Cornuz J, Robbins J, Fried LP, Ladenson PW, Vittinghoff E, Gottdiener JS, Newman AB. Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The cardiovascular health study. J Am Coll Cardiol. 2008;52:1152–9.CrossRefGoogle Scholar
  45. 45.
    Gencer B, Collet TH, Virgini V, Bauer DC, Gussekloo J, Cappola AR, Nanchen D, den Elzen WPJ, Balmer P, Luben RN, Iacoviello M, Triggiani V, Cornuz J, Newman AB, Khaw KT, Jukema JW, Westendorp RGJ, Vittinghoff E, Aujesky D, Rodondi N, Thyroid Studies Collaboration. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from six prospective cohorts. Circulation. 2012;126:1040–9.CrossRefGoogle Scholar
  46. 46.
    Iervasi G, Molinaro S, Landi P, Taddei MC, Galli E, Mariani F, L’Abbate A, Pingitore A. Association between increased mortality mortality and mild thyroid dysfunction in cardiac patients. Arch Intern Med. 2007;167:1526–32.CrossRefGoogle Scholar
  47. 47.
    Iacoviello M, Guida P, Guastamacchia E, Triggiani V, Forleo C, Catanzaro R, Cicala M, Basile M, Sorrentino S, Favale S. Prognostic role of sub-clinical hypothyroidism in chronic heart failure outpatients. Curr Pharm Des. 2008;14:2686–92.CrossRefGoogle Scholar
  48. 48.
    Silva-Tinoco R, Castillo-Martìnez L, Orea-Tejeda A, Orozco-Gutièrez JJ, Vàzquez-DÃaz O, Montanò-Hernàndez P, Flores-Rebollar A, Reza-Albarràn A. Developing thyroid disorders is associated with poor prognosis factors in patient with stable chronic heart failure. Int J Cardiol. 2011;147:e24–5.CrossRefGoogle Scholar
  49. 49.
    Nanchen D, Gussekloo J, Westendorp RG, Stott DJ, Jukema JW, Trompet S, Ford I, Welsh P, Sattar N, Macfarlane PW, Mooijaart SP, Rodondi N, de Craen AJ, PROSPER Group. Subclinical thyroid dysfunction and the risk of heart failure in older persons at high cardiovascular risk. J Clin Endocrinol Metab. 2012;97:852–61.CrossRefGoogle Scholar
  50. 50.
    Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, Konstam MA, Mancini DM, Rahko PS, Silver MA, Stevenson LW, Yancy CW. 2009 focused update: ACCF/AHA guidelines for the diagnosis and Management of Heart Failure in adults: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 1977–2016;200:119.Google Scholar
  51. 51.
    Kahaly GJ. Cardiovascular and atherogenic aspects of subclinical hypothyroidism. Thyroid. 2000;10:665–79.CrossRefGoogle Scholar
  52. 52.
    Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, Asvold BO, Iervasi G, Imaizumi M, Collet TH, Bremner A, Maisonneuve P, Sgarbi JA, Khaw KT, Vanderpump MP, Newman AB, Cornuz J, Franklyn JA, Westendorp RG, Vittinghoff E, Gussekloo J, Thyroid Studies Collaboration. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010;304:1365–74.CrossRefGoogle Scholar
  53. 53.
    Schwimmer D, Vogel M, Mc Gavack TH. Clinical manifestations in forty cases of myxedema. J Clin Endocrinol Metab. 1947;7:468.PubMedGoogle Scholar
  54. 54.
    Keating FRJ, Parkin TW, Selby JB, Dickinson LS. Treatment of heart disease associated with myxedema. Prog Cardiovasc Dis. 1961;3:364–81.CrossRefGoogle Scholar
  55. 55.
    Ladenson PW, Levin AA, Ridgway EC, Daniels GH. Worsening of angina, myocardial infarction and death can occur when L-thyroxine therapy is started with a full dose in older patients with ischemic heart disease. Am J Med. 1984;77:261–6.CrossRefGoogle Scholar
  56. 56.
    Biondi B, Wartofsky L. Treatment with thyroid hormone. Endocr Rev. 2014;35:433–512.CrossRefGoogle Scholar
  57. 57.
    Monzani F, Di Bello V, Caraccio N, Bertini A, Giorgi D, Giusti C, Ferranini E. Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. J Clin Endocrinol Metab. 2001;86:1110–5.CrossRefGoogle Scholar
  58. 58.
    Yazici M, Gorgulu S, Sertbas Y, Erbilen E, Albayrak S, Yildiz O, Uyan C. Effects of thyroxin therapy on cardiac function in patients with subclinical hypothyroidism: index of myocardial performance in the evaluation of left ventricular function. Int J Cardiol. 2004;95:135–43.CrossRefGoogle Scholar
  59. 59.
    Taddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L, Salvetti A, Ferrannini E, Monzani F. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. J Clin Endocrinol Metab. 2003;88:3731–7.CrossRefGoogle Scholar
  60. 60.
    Monzani F, Caraccio N, Kozakowa M, Dardano A, Vittone F, Virdis A, Taddei S, Palombo C, Ferrannini E. Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study. J Clin Endocrinol Metab. 2004;89:2099–106.CrossRefGoogle Scholar
  61. 61.
    Nagasaki T, Inaba M, Henmi Y, Kumeda Y, Ueda M, Tahara H, Sugiguchi S, Fujiwara S, Emoto M, Ishimura E, Onoda N, Ishikawa T, Nishizawa Y. Decrease in carotid intima-media thickness in hypothyroid patients after normalization of thyroid function. Clin Endocrinol. 2003;59:607–12.CrossRefGoogle Scholar
  62. 62.
    Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab. 2007;92:1715–23.CrossRefGoogle Scholar
  63. 63.
    Villar HC, Saconato H, Valente O, Atallah AN. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst Rev. 2007;CD003419.Google Scholar
  64. 64.
    Razvi S, Weaver JU, Vanderpump MP, Pearce SH. The incidence of ischemic heart disease and mortality in people with subclinical hypothyroidism: reanalysis of the Whickham survey cohort. J Clin Endocrinol Metab. 2010;95:1734–40.CrossRefGoogle Scholar
  65. 65.
    Razvi S, Weaver JU, Butler TJ, Pearce SH. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Arch Intern Med. 2012;72(10):811–7.Google Scholar
  66. 66.
    Ochs N, Auer R, Bauer DC, Nanchen D, Gussekloo J, Cornuz J, Rodondi N. Meta-analysis: subclinicalthyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med. 2008;148:832–45.CrossRefGoogle Scholar
  67. 67.
    Razvi S, Shakoor A, Vanderpump M, Weaver JU, Pearce SH. The influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: a metaanalysis. J Clin Endocrinol Metab. 2008;93:2998–3007.CrossRefGoogle Scholar
  68. 68.
    Atzmon G, Barzilai N, Hollowell JG, Surks MI, Gabriely I. Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab. 2009;94:1251–4.CrossRefGoogle Scholar
  69. 69.
    Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frölich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004;292:2591–9.CrossRefGoogle Scholar
  70. 70.
    Waring AC, Arnold AM, Newman AB, Bùzková P, Hirsch C, Cappola AR. Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study. J Clin Endocrinol Metab. 2012;97:3944–50.CrossRefGoogle Scholar
  71. 71.
    Somwaru LL, Arnold AM, Joshi N, Fried LP, Cappola AR. High frequency of and factors associated with thyroid hormone over-replacement and under-replacement in men and women aged 65 and over. J Clin Endocrinol Metab. 2009;94:1342–5.CrossRefGoogle Scholar
  72. 72.
    Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, Burke GL, Tracy RP, Ladenson PW. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA. 2006;295:1033–41.CrossRefGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Clinical Medicine and SurgeryUniversity of Naples Federico IINaplesItaly
  2. 2.Department of Medicine IJohannes Gutenberg University Medical CenterMainzGermany

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