Skip to main content
Clinical Cardiology logoLink to Clinical Cardiology
. 2009 Feb 3;23(6):402–408. doi: 10.1002/clc.4960230605

Hyperthyroid heart disease

Bahaa M Fadel 1,, Samer Ellahham 2, Joseph Lindsay Jr 2, Matthew D Ringel 3, Leonard Wartofsky 3, Kenneth D Burman 3
PMCID: PMC6654928  PMID: 10875028

Abstract

The heart is an organ sensitive to the action of thyroid hormone, and measurable changes in cardiac performance are detected with small variations in thyroid hormone serum concentrations. Most patients with hyperthyroidism experience cardiovascular manifestations, and the most serious complications of hyperthyroidism occur as a result of cardiac involvement. Recent studies provide important insights into the molecular pathways that mediate the action of thyroid hormone on the heart and allow a better understanding of the mechanisms that underlie the hemodynamic and clinical manifestations of hyperthyroidism. Several cardiovascular conditions and drugs can interfere with thyroid hormone levels and may pose a difficulty in interpretation of laboratory data in patients with suspected thyroid heart disease. The focus of this report is a review of the current knowledge of thyroid hormone action on the heart and the clinical and hemodynamic laboratory findings as well as therapeutic management of patients with hyperthyroid heart disease.

Keywords: hyperthyroidism, thyroid hormone, heart failure, atrial fibrillation

Full Text

The Full Text of this article is available as a PDF (782.2 KB).

Reference

  • 1. Tsai MJ, O'Malley BW: Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Ann Rev Biochem 1994; 63: 451–486 [DOI] [PubMed] [Google Scholar]
  • 2. Davis PJ, Davis FB: Nongenomic actions of thyroid hormone. Thyroid 1996; 6: 497–504 [DOI] [PubMed] [Google Scholar]
  • 3. Ribeiro RC, Apriletti JW, West BL, Wagner RL, Fletterick RJ, Schaufele F, Baxter JD: The molecular biology of thyroid hormone action. Ann N Y Acad Sci 1995; 758: 366–389 [DOI] [PubMed] [Google Scholar]
  • 4. Leng X, Blanco J, Tsai SY, Ozato K, O'Malley BW, Tsai MJ: Mechanisms for synergistic activation of thyroid hormone receptor and retinoid X receptor on different response elements. J Biol Chem 1994; 269: 31436–31442 [PubMed] [Google Scholar]
  • 5. Tsika RW, Bahl JJ, Leinwand LA, Morkin E: Thyroid hormone regulates expression of a transfected human alpha‐myosin heavy‐chain fusion gene in fetal rat heart cells. Proc Natl Acad Sci USA 1990; 87: 379–383 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Zarain‐Herzberg A, Marques J, Sukovich D, Periasamy M: Thyroid hormone receptor modulates the expression of the rabbit cardiac sarco (endo) plasmic reticulum Ca(2+)‐ATPase gene. J Biol Chem 1994; 269: 1460–1467 [PubMed] [Google Scholar]
  • 7. Orlowski J, Lingrel JB: Thyroid and glucocorticoid hormones regulate the expression of multiple Na, K‐ATPase genes in cultured neonatal rat cardiac myocytes. J Biol Chem 1990; 265: 3462–3470 [PubMed] [Google Scholar]
  • 8. Bahouth SW: Thyroid hormones transcriptionally regulate the beta 1 ‐adrenergic receptor gene in cultured ventricular myocytes. J Biol Chem 1991; 266: 15863–15869 [PubMed] [Google Scholar]
  • 9. Averyhart‐Fullard V, Fraker LD, Murphy AM, Solaro RJ: Differential regulation of slow‐skeletal and cardiac troponin I mRNA during development and by thyroid hormone in rat heart. J Mol Cell Cardiol 1994; 26: 609–616 [DOI] [PubMed] [Google Scholar]
  • 10. Fullerton MJ, Stuchbury S, Krozowski ZS, Funder JW: Altered thyroidal status and the in vivo synthesis of atrial natriuretic peptide in the rat heart. Mol Cell Endocrinol 1990; 69: 227–233 [DOI] [PubMed] [Google Scholar]
  • 11. Morkin E: Regulation of myosin heavy chain genes in the heart. Circulation 1993; 87: 1451–1460 [DOI] [PubMed] [Google Scholar]
  • 12. Izumo S, Nadal‐Ginard B, Mahdavi V: All members of the MHC multigene family respond to thyroid hormone in a highly tissue‐specific manner. Science 1986; 231: 597–600 [DOI] [PubMed] [Google Scholar]
  • 13. Hammond HK, White FC, Buxton IL, Saltzstein P, Brunton LL, Longhurst JC: Increased myocardial beta‐receptors and adrenergic responses in hypothyroid pigs. Am J Physiol 1987; 252:H283‐H290 [DOI] [PubMed] [Google Scholar]
  • 14. Waldstein SS: Thyroid‐catecholamine interrelations. Ann Rev Med 1966; 17: 123–132 [DOI] [PubMed] [Google Scholar]
  • 15. Nishizawa Y, Hamada N, Fujii S, Morii H, Okuda K: Serum dopa‐mine‐beta‐hydroxylase activity in thyroid disorders. J Clin Endo‐crinol Metab 1974; 39: 599–602 [DOI] [PubMed] [Google Scholar]
  • 16. Levey GS, Skelton CL, Epstein SE: Influence of hyperthyroidism on the effects of norepinephrine on myocardial adenyl cyclase activity and contractile state. Endocrinology 1969; 85: 1004–1009 [DOI] [PubMed] [Google Scholar]
  • 17. Hoit BD, Khoury SF, Shao Y, Gabel M, Liggett SB, Walsh RA: Effects of thyroid hormone on cardiac beta‐adrenergic responsiveness in conscious baboons. Circulation 1997;96 592–598 [DOI] [PubMed] [Google Scholar]
  • 18. Klemperer JD, Klein I, Gomez M, Helm RE, Ojamaa K, Thomas SJ, Isom OW, Krieger K: Thyroid hormone treatment after coronary‐artery bypass surgery. N Engl J Med 1995; 333: 1522–1527 [DOI] [PubMed] [Google Scholar]
  • 19. Dudley SC Jr, Baumgarten CM: Bursting of cardiac sodium channels after acute exposure to 3,5,3′‐triiodo‐L‐thyronine. Circ Res 1993; 73: 301–313 [DOI] [PubMed] [Google Scholar]
  • 20. Walker JD, Crawford FA Jr, Mukherjee R, Spinale FG: The direct effects of 3,5,3′‐triiodo‐L‐thyronine (T3) on myocyte contractile processes. Insights into mechanisms of action. J Thorac Cardio‐vasc Surg 1995; 110: 1369–1379 [DOI] [PubMed] [Google Scholar]
  • 21. Park KW, Dai HB, Ojamaa K, Lowenstein E, Klein I, Sellke FW: The direct vasomotor effect of thyroid hormones on rat skeletal muscle resistance arteries. Anesth Analg 1997; 85: 734–738 [DOI] [PubMed] [Google Scholar]
  • 22. Ojamaa K, Klemperer JD, Klein I: Acute effects of thyroid hormone on vascular smooth muscle. Thyroid 1996; 6: 505–512 [DOI] [PubMed] [Google Scholar]
  • 23. Anthonisen P, Holst E, Thomsen A: Determination of cardiac output and other hemodynamic data in patients with hyper‐ and hypothyroidism, using dye dilution technique. Scand J Clin Lab Invest 1960; 12: 472–480 [DOI] [PubMed] [Google Scholar]
  • 24. DeGroot WJ, Leonard JJ: Hyperthyroidism as a high cardiac output state. Am Heart J 1970; 79: 265–275 [DOI] [PubMed] [Google Scholar]
  • 25. Resnick LM, Laragh JH: Plasma renin activity in syndromes of thyroid hormone excess and deficiency. Life Sci 1982; 30: 585–586 [DOI] [PubMed] [Google Scholar]
  • 26. Gibson JG, Harris AW: Clinical studies of the blood volume of hyperthyroidism and myxedema. J Clin Invest 1938; 18: 59–74 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. Merillon JP, Passa P, Chastre J, Wolf A, Gourgon R: Left ventricular function and hyperthyroidism. Br Heart J 1981; 46: 137–143 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Mintz G, Pizzarello R, Klein I: Enhanced left ventricular diastolic function in hyperthyroidism: Noninvasive assessment and response to treatment. J Clin Endocrinol Metab 1991; 73: 146–150 [DOI] [PubMed] [Google Scholar]
  • 29. Lerman J, Means HJ: Cardiovascular symptomatology in exoph‐talmic goiter. Am Heart J 1932; 8: 55–65 [Google Scholar]
  • 30. Channick BJ, Adlin EV, Marks AD, Denenberg SBS, McDonough MT, Chakko CS, Spann JF: Hypothyroidism and mitral‐valve prolapse. N Engl J Med 1981; 305: 497–500 [DOI] [PubMed] [Google Scholar]
  • 31. Brauman A, Algom M, Gilboa Y, Ramot Y, Golik A, Stryjer D: Mitral valve prolapse in hyperthyroidism of two different origins. Br Heart J 1985; 53: 374–377 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Sandler G, Wilson GM: The nature and prognosis of heart disease in thyrotoxicosis: A review of 150 patients treated with 1311. Q J Med 1959; 28: 347–360 [PubMed] [Google Scholar]
  • 33. Nordyke RA, Gilbert FI Jr, Harada AS: Graves' disease. Influence of age on clinical findings. Arch Intern Med 1988; 148: 626–631 [DOI] [PubMed] [Google Scholar]
  • 34. Petersen P, Hansen JM: Stroke in thyrotoxicosis with atrial fibrillation. Stroke 1988; 19: 15–18 [DOI] [PubMed] [Google Scholar]
  • 35. Iwasaki T, Naka M, Hiramatsu K, Yamada T, Niwa A, Aizawa T, Murakami M, Ishihara M, Miyahara Y: Echocardiographic studies on the relationship between atrial fibrillation and atrial enlargement in patients with hyperthyroidism of Graves' disease. Cardiology 1989; 76: 10–17 [DOI] [PubMed] [Google Scholar]
  • 36. Sawin CT, Geller A, Wolf PA, Belanger AJ, Baker E, Bacharach P, Wilson PW, Benjamin EJ, D'Agostino RB: Low serum thyrotripin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994; 331: 1249–1252 [DOI] [PubMed] [Google Scholar]
  • 37. Marqusee E, Haden ST, Utiger RD: Subclinical thyrotoxicosis. Endocrinol Metab Clin North Am 1998; 27: 37–49 [DOI] [PubMed] [Google Scholar]
  • 38. Montereggi A, Marconi P, Olivotto I, Castelli G, Dolara A, Luisi ML, Gheri RG: Signal‐averaged P‐wave duration and risk of paroxysmal atrial fibrillation in hyperthyroidism. Am J Cardiol 1996; 77: 266–269 [DOI] [PubMed] [Google Scholar]
  • 39. Forfar JC, Muir AL, Sawers SA, Toft AD: Abnormal left ventricular function in hyperthyroidism: Evidence for a possible reversible cardiomyopathy. N Engl J Med 1982; 307: 1165–1170 [DOI] [PubMed] [Google Scholar]
  • 40. Klein I, Hong C: Effects of thyroid hormone on cardiac size and myosin content of the heterotopically transplanted rat heart. J Clin Invest 1986; 77: 1694–1698 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. Klein I, Ojamaa K: Thyrotoxicosis and the heart. Endocrinol Metab Clin North Am 1980; 27: 51–62 [DOI] [PubMed] [Google Scholar]
  • 42. Ikram H: The nature and prognosis of thyrotoxic heart disease. Q J Med 1985; 54: 19–28 [PubMed] [Google Scholar]
  • 43. Kantharia BK, Richards HB, Battaglia J: Reversible dilated cardiomyopathy: An unusual case of thyrotoxicosis. Am Heart J 1995; 129: 1030–1032 [DOI] [PubMed] [Google Scholar]
  • 44. Cruz FE, Cheriex EC, Smeets JL, Atie J, Peres AK, Penn OC, Brugada P, Wellens HJ: Reversibility of tachycardia‐induced cardiomyopathy after cure of incessant supraventricular tachycardia. J Am Coll Cardiol 1990; 16: 739–744 [DOI] [PubMed] [Google Scholar]
  • 45. Sachs RN, Vignot M, Modigliani E, Perennec‐Cardinalli J, Kem‐eny JL, Amouroux J, Hatt PY, Lanfranchi J: Absence of ultra‐structural histological lesions of the myocardium in cardiac insufficiency of hyperthyroidism. Ann Med Interne (Paris) 1986; 137: 375–378 [PubMed] [Google Scholar]
  • 46. Saito I, Saruta T: Hypertension in thyroid disorders. Endocrinol Metab Clin North Am 1994; 23: 379–386 [PubMed] [Google Scholar]
  • 47. Seth J, Kellett HA, Caldwell G, Sweeting VM, Beckett GJ, Gow SM, Toft AD: A sensitive immunoradiometric assay for serum thyroid stimulating hormone: A replacement for the thyrotrophin releasing hormone test? Br Med J 1984; 289: 1334–1336 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48. Forfar JC: Atrial fibrillation and the pituitary‐thyroid axis: A re‐evaluation. Heart 1997; 77: 3–4 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49. Reinhardt W, Mocker V, Jockenhovel F, Olbricht T, Reinwein D, Mann K, Sadony V: Influence of coronary artery bypass surgery on thyroid hormone parameters. Horm Res 1997; 47: 1–8 [DOI] [PubMed] [Google Scholar]
  • 50. Harjai KJ, Licata AA: Effects of amiodarone on thyroid function (see comments). Ann Intern Med 1997; 126: 63–73 [DOI] [PubMed] [Google Scholar]
  • 51. Hellman R, Kelly KL, Mason WD: Propranolol for thyroid storm. N Engl J Med 1997; 297: 671–672 [DOI] [PubMed] [Google Scholar]
  • 52. Geffner DL, Hershman JM: Beta‐adrenergic blockade for the treatment of hyperthyroidism. Am J Med 1992; 93: 61–68 [DOI] [PubMed] [Google Scholar]
  • 53. Shenfield GM: Influence of thyroid dysfunction on drug pharmacokinetics. Clin Pharmacokinet 1981; 6: 275–297 [DOI] [PubMed] [Google Scholar]
  • 54. Chopra IJ, Huang TS, Hurd RE, Solomon DH: A study of cardiac effects of thyroid hormones: Evidence for amelioration of the effects of thyroxine by sodium ipodate. Endocrinology 1984; 114: 2039–2045 [DOI] [PubMed] [Google Scholar]
  • 55. Klein I, Becker DV, Levey GS: Treatment of hyperthyroid disease. Ann Intern Med 1994; 121: 281–288 [DOI] [PubMed] [Google Scholar]
  • 56. Morrow DH, Gaffney TE, Braunwald E: Studies on digitalis: VIII. Effect of autonomic innervation and of myocardial cathecolamine stores upon the cardiac action of ouabain. J Pharmacol Exp Ther 1963; 140: 236–245 [Google Scholar]
  • 57. Chaudhury S, Ismail‐Beigi F, Gick GG, Levenson R, Edelman IS: Effect of thyroid hormone on the abundance of Na, K‐adenosine triphosphatase alpha‐subunit messenger ribonucleic acid. Mol Endocrinol 1987; 1: 83–89 [DOI] [PubMed] [Google Scholar]
  • 58. Isley WL, Dahl S, Gibbs H: Use of esmolol in managing a thyrotoxic patient needing emergency surgery. Am J Med 1990; 89: 122–123 [DOI] [PubMed] [Google Scholar]
  • 59. Nakazawa HK, Sakurai K, Hamada N, Momotani N, Ito K: Management of atrial fibrillation in the post‐thyrotoxic state. Am J Med 1982; 72: 903–906 [DOI] [PubMed] [Google Scholar]

Articles from Clinical Cardiology are provided here courtesy of Wiley

RESOURCES