Thyroid Disease and the Heart
Open accessAbstract
The cardiovascular signs and symptoms of thyroid disease are some of the most profound and clinically relevant findings that accompany both hyperthyroidism and hypothyroidism. On the basis of the understanding of the cellular mechanisms of thyroid hormone action on the heart and cardiovascular system, it is possible to explain the changes in cardiac output, cardiac contractility, blood pressure, vascular resistance, and rhythm disturbances that result from thyroid dysfunction. The importance of the recognition of the effects of thyroid disease on the heart also derives from the observation that restoration of normal thyroid function most often reverses the abnormal cardiovascular hemodynamics. In the present review, we discuss the appropriate thyroid function tests to establish a suspected diagnosis as well as the treatment modalities necessary to restore patients to a euthyroid state. We also review the alterations in thyroid hormone metabolism that accompany chronic congestive heart failure and the approach to the management of patients with amiodarone-induced alterations in thyroid function tests.
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At the cardiac level, stimulation of β-type thyroid-hormone receptors up-regulates calcium-dependent ATPase pumps of the endoplasmic reticulum and reduces expression of Phospholamban, resulting in increased myocardial relaxation and a positive inotropic effect.
“At the cardiac level, stimulation of the β-type thyroid-hormone receptors determines an up-regulation of the calcium-dependent ATPase pumps of the endoplasmic reticulum and a reduced expression of the Phospholamban protein resulting in an inhibitory action.”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
The positive chronotropic effect of thyroid hormones derives mainly from a direct action of T3 on genes regulating cardiac-pacemaker activity.
“The positive chronotropic effect derives mainly from a direct action of T3 on the genes that regulate the activity of the cardiac-pacemaker.”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
In severe hypothyroidism, chronic and pericardial interstitial edema with reduced myocardial contractility can progress to cardiac tamponade.
“In the most severe forms, chronic and pericardial interstitial edema, associated with reduced myocardial contractility, can progress to cardiac tamponade [1, 3].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
Overt hypothyroidism causes interstitial accumulation of glycosaminoglycans that attracts water from the endovascular compartment, reducing effectiveness of medical therapy.
“Overt hypothyroidism causes an interstitial accumulation of glycosaminoglycans that attracts water from the endovascular compartment, reducing the effectiveness of medical therapy.”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
At the peripheral level, stimulation of α-1 thyroid receptors on endothelial and smooth muscle cells reduces peripheral resistance, causing a decrease in diastolic pressure.
“At the peripheral level, the stimulation of the α-1 thyroid receptors, expressed by the endothelial and smooth muscle cells of the vessels, reduces peripheral resistance causing a decrease in diastolic pressure [1, 6].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
Tachyarrhythmia associated with hemodynamic alterations in hyperthyroidism is often the cause of high-rate heart failure, especially in patients with concomitant risk factors.
“The presence of tachyarrhythmia associated with the previously described hemodynamic alterations is often the cause of high-rate heart failure, especially in patients with concomitant risk factors [1, 6].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
At the renal level, reduced perfusion from peripheral vasodilation activates the renin-angiotensin-aldosterone system, with sodium-retentive action and increased circulating volume.
“At the renal level, this effect leads to a reduced perfusion with consequent activation of the renin–angiotensin–aldosterone system (to which a direct effect of T3 via thyroid β-1 receptors probably also contributes) with a sodium-retentive action and an increase in circulating volume [1, 6].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
A role of catecholaminergic stimulation in the positive chronotropic effect of thyroid hormones seems unlikely.
“Although a role of cathecolaminergic stimulation has been hypothesized, this seems unlikely.”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
Hypothyroidism reduces activity of the myocardial pacemaker and lengthens QT intervals, which can lead to advanced atrio-ventricular blocks or torsades-de-pointes resulting in ventricular tachycardia.
“The presence of hypothyroidism also involves a reduction in the activity of the myocardial pacemaker and a lengthening of the QT intervals which can lead to the appearance of advanced atrio-ventricular blocks or torsades-de-pointes resulting in ventricular tachycardia [1, 3].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
Thyrotoxicosis determines an imbalance of coagulative homeostasis towards hypercoagulability and reduced fibrinolysis, characterized by increased circulating levels of factor VIII, IX, fibrinogen and Von Willebrand factor.
“thyrotoxicosis determines an imbalance of coagulative homeostasis towards a state of hypercoagulability and reduced fibrinolysis characterized by an increase in the circulating levels of factor VIII, IX, fibrinogen and Von Willebrand factor [1, 6]”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
T3 induces an increase in expression of β1-adrenergic receptors on myocardiocytes, increasing myocardial sensitivity to catecholamines, while simultaneously inhibiting cardiac expression of catalytic isoforms of adenylate-cyclase, keeping the endocellular response unchanged.
“Indeed, T3 induces an increase in the expression of β1-adrenergic receptors on myocardiocytes, increasing myocardial sensitivity to the action of catecholamines, as it simultaneously inhibits the cardiac expression of the catalytic isoforms of adenylate–cyclase, keeping the endocellular response unchanged [1, 6].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
Overt hypothyroidism is often associated with early diastolic dysfunction, which together with diastolic hypertension and/or other risk factors can lead to difficult-to-treat heart failure.
“Echocardiographic studies have shown that overt hypothyroidism is often associated with early diastolic dysfunction which, together with the frequent occurrence of diastolic hypertension and/or other risk factors in these patients, can lead to difficult-to-treat heart failure [1, 3].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
Only 5% of subjects with thyrotoxicosis under the age of 60 have atrial fibrillation.
“Conversely, only 5% of subjects with thyrotoxicosis under the age of 60 have AF [1, 6].”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
Patients with overt hyperthyroidism experience atrial fibrillation at a rate ranging from 10 to 25%, with higher percentages in males over 60 years and in those with higher free T4 values.
“Patients with overt hyperthyroidism, at a rate ranging from 10 to 25%, experience atrial fibrillation (AF) with even higher percentages in males over 60 years of age and in those with higher free T4 (FT4) values.”
From Thyroid and heart, a clinically relevant relationship (2021) · cites this paper as [1]
The thyroid hormone is one of the key regulators of cardiac function and cardiovascular hemodynamics.
“The thyroid hormone is one of the key regulators of cardiac function and cardiovascular hemodynamics; therefore, inadequate thyroid hormone levels impair the relaxation of vascular smooth muscle cells and decrease cardiac contractility by regulating calcium uptake and the expression of several contractile proteins in cardiomyocytes.37,38”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [37]
Low thyroid hormone levels increase systemic vascular resistance and induce endothelial dysfunction by reducing nitric oxide availability.
“Low thyroid hormone levels also increase systemic vascular resistance and induce endothelial dysfunction by reducing nitric oxide availability.37,38,39”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [37]
Excess thyroid hormone increases cardiac output by affecting stroke volume and heart rate.
“excess increases cardiac output by affecting stroke volume and heart rate(6,71).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [71]
Patients with severe hyperthyroidism may have coronary vasospasm leading to chest pain at rest or myocardial ischemia.
“Patients with severe hyperthyroidism may have coronary vasospasm leading to chest pain at rest or myocardial ischemia(6,70,71,79).”
From Thyroid Hormones and Cardiovascular Function and Diseases (2018) · cites this paper as [71]
Life-threatening thyrotoxicosis or thyroid storm is a rare disorder characterized by multisystem involvement and mortality rates in the range of 8%-25% in modern series.
“Life-threatening thyrotoxicosis or thyroid storm is a rare disorder characterized by multisystem involvement and mortality rates in the range of 8%-25% in modern series (25,72,226,227).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [25]
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“The cardiac ramifications from hyperthyroidism are well described and may include palpitations, tachycardia, exercise intolerance, dyspnea on exertion, widened pulse pressure, cardiac ischemia, or atrial fibrillation.(27) In the acute setting of thyroid storm, these findings can become life threatening.”
BackgroundThyroid dysfunction and kidney disease: An update
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Cardiovascular involvement in patients with different causes of hyperthyroidism
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Cardiovascular Phenotype in Turner Syndrome—Integrating Cardiology, Genetics, and Endocrinology
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III Diretriz Brasileira de Insuficiência Cardíaca Crônica
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Thyroid Hormone and the Cardiovascular System
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Self-citationA critical review and meta-analysis of the association between overt hyperthyroidism and mortality
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Hyperthyroidism and Thyrotoxicosis
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Thyroid Disease and the Cardiovascular System
Danzi, S. E., & Klein, I. L. (2014) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2014.02.005 · Cited by 160 · see citing works
Self-citationClinical practice guidelines for the management of hypothyroidism
Brenta, G., Vaisman, M., Sgarbi, J. A., Bergoglio, L., de Andrada, N. C., Bravo, P. P., Orlandi, A. M., & Graf, H. (2013) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302013000400003 · Cited by 161 · see citing works
Effects of amiodarone therapy on thyroid function
Cohen-Lehman, J., Dahl, P., Danzi, S., & Klein, I. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.225 · Cited by 157 · see citing works
Self-citationSubclinical thyroid dysfunction and cardiovascular diseases: 2016 update
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Hypertension in Thyroid Disorders
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Clinical Features and Hospital Outcomes in Thyroid Storm: A Retrospective Cohort Study
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Thyroid Function in Heart Failure and Impact on Mortality
Mitchell, J. E., Hellkamp, A. S., Mark, D. B., Anderson, J., Johnson, G. W., Poole, J. E., Lee, K. L., & Bardy, G. H. (2013) · JACC Heart Failure · doi:10.1016/j.jchf.2012.10.004 · Cited by 140 · see citing works
Shin, D. H., Lee, M. J., Kim, S. J., Oh, H. J., Kim, H. R., Han, J. H., Koo, H. M., Doh, F. M., Park, J. T., Han, S. H., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1663 · Cited by 138 · see citing works
Kusumoto, F. M., Schoenfeld, M. H., Barrett, C., Edgerton, J. R., Ellenbogen, K. A., Gold, M. R., Goldschlager, N., Hamilton, R. M., Joglar, J. A., Kim, R. J., et al. (2018) · Heart Rhythm · doi:10.1016/j.hrthm.2018.10.036 · Cited by 138 · see citing works
Kars, M., Delgado, V., Holman, E. R., Feelders, R. A., Smit, J. W. A., Romijn, J. A., Bax, J. J., & Pereira, A. M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2658 · Cited by 135 · see citing works
Dahl, P., Danzi, S. E., & Klein, I. L. (2008) · Current Heart Failure Reports · doi:10.1007/s11897-008-0026-9 · Cited by 136 · see citing works
Self-citationKusumoto, F. M., Schoenfeld, M. H., Barrett, C., Edgerton, J. R., Ellenbogen, K. A., Gold, M. R., Goldschlager, N. F., Hamilton, R. M., Joglar, J. A., Kim, R. J., et al. (2019) · Heart Rhythm · doi:10.1016/j.hrthm.2018.10.037 · Cited by 131 · see citing works
The role of thyroid hormone in the pathophysiology of heart failure: clinical evidence
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Thyroid Hormone Plays an Important Role in Cardiac Function: From Bench to Bedside
Yamakawa, H., Kato, T., Noh, J. Y., Yuasa, S., Kawamura, A., Fukuda, K., & Aizawa, Y. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.606931 · Cited by 137 · see citing works
“In another study, the authors hypothesized that T3 primarily regulates genes that control cardiac pacemaker cells, exerting a positive chronotropic effect in these cells (Klein and Danzi, 2016).”
BackgroundLineage restricted progenitors for the repopulation of decellularized heart
Ng, S. L. J., Narayanan, K., Gao, S., & Wan, A. C. A. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.06.065 · Cited by 130 · see citing works
Thyrotropin Levels and Risk of Fatal Coronary Heart Disease: The HUNT Study
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Hypothyroidism and Thyroiditis
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Thyroid function and the risk of dementia
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Atrial fibrillation from the pathologist’s perspective
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I Diretriz Latino-Americana para avaliação e conduta na insuficiência cardíaca descompensada
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Dilated cardiomyopathy and chronic cardiac inflammation: Pathogenesis, diagnosis and therapy
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Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality
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“Age was an independent predictor of AF in our patient opulation, as in other studies (2,6).”
BackgroundResultDaytime napping and mortality, with a special reference to cardiovascular disease: the JACC study
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Self-citationPotential therapeutic applications of thyroid hormone analogs
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“In the second step, histone acetyltransferases are exchanged for coactivators including thyroid hormone receptor associated protein (TRAP)220, TRAP230 or transcriptional intermediary factor 2, which activate transcription by binding RNA polymerase II and forming the TRAP–mediator complex”
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Heart Failure as a Multiple Hormonal Deficiency Syndrome
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Pericardial diseases in patients with hypothyroidism
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The epidemiology of thyroid diseases in the Arab world: A systematic review
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Engineered Microenvironments for Maturation of Stem Cell Derived Cardiac Myocytes
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Thyroid dysfunction in the elderly
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Thyroid hormone action in postnatal heart development
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“3) (Klein and Danzi, 2007; Maillet et al., 2013).”
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The Role of Thyroid Hormones in Heart Failure
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Is subclinical hypothyroidism a cardiovascular risk factor in the elderly?
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Thyroid hormones and the cardiovascular system: Pathophysiology and interventions
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Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
Ferrandino, G., Kaspari, R. R., Spadaro, O., Reyna‐Neyra, A., Perry, R. J., CARDONE, R. L., Kibbey, R. G., Shulman, G. I., Dixit, V. D., & Carrasco, N. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707797114 · Cited by 77 · see citing works
- Authors
- Klein, I., & Danzi, S.
- Affiliations
- Feinstein Institute for Medical Research (US)
- Venue
- Circulation
- Published
- 2007-10-09
- Volume
- 116
- Issue
- 15
- Pages
- 1725-1735
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2124101478
- Cited by
- 1,324
- References
- 121
- Citations by year
- 2026: 76 · 2025: 64 · 2024: 61 · 2023: 95 · 2022: 105 · 2021: 83 · 2020: 82 · 2019: 72 · 2018: 72 · 2017: 79 · 2016: 76 · 2015: 88 · 2014: 59 · 2013: 76 · 2012: 65
- FWCI
- 29.59
- Type
- journal article
- Language
- en
- Update notices
- correction (2008-01-22)
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (M01RR018535)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- thyroid dysfunction, hyperthyroidism, hypothyroidism, cardiac output, cardiac contractility, blood pressure, vascular resistance, cardiac arrhythmias, thyroid function tests, thyroid hormone replacement, congestive heart failure, thyroid hormone metabolism, amiodarone, euthyroidism
- MeSH terms
- Cardiovascular Diseases, Gene Expression Regulation, Heart, Humans, Renin-Angiotensin System, Thyroid Diseases, Thyroid Function Tests, Thyroid Hormones, Myocytes, Cardiac
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