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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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In the citing paper
“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]
In the citing paper
“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 the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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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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 142
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
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
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
Dahl, P., Danzi, S. E., & Klein, I. L. (2008) · Current Heart Failure Reports · doi:10.1007/s11897-008-0026-9 · Cited by 136
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
The role of thyroid hormone in the pathophysiology of heart failure: clinical evidence
Galli, E., Pingitore, A., & Iervasi, G. (2010) · Heart Failure Reviews · doi:10.1007/s10741-008-9126-6 · Cited by 132
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
“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
Thyrotropin Levels and Risk of Fatal Coronary Heart Disease: The HUNT Study
Åsvold, B. O., Bjøro, T., Nilsen, T. I. L., Gunnell, D., & Vatten, L. J. (2008) · Archives of Internal Medicine · doi:10.1001/archinte.168.8.855 · Cited by 125
Hypothyroidism and Thyroiditis
Brent, G. A., & Davies, T. F. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-0324-5.00013-4 · Cited by 115
Thyroid function and the risk of dementia
Chaker, L., Wolters, F. J., Bos, D., Korevaar, T. I. M., Albert Hofman, D., van der Lugt, A., Koudstaal, P. J., Franco, O. H., Dehghan, A., Vernooij, M. W., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000003227 · Cited by 115
Atrial fibrillation from the pathologist’s perspective
Corradi, D. (2013) · Cardiovascular Pathology · doi:10.1016/j.carpath.2013.12.001 · Cited by 119
Cerignoli, F., Charlot, D., Whittaker, R., Ingermanson, R., Gehalot, P., Savchenko, A., Gallacher, D. J., Towart, R., Price, J. H., McDonough, P. M., et al. (2012) · Journal of Pharmacological and Toxicological Methods · doi:10.1016/j.vascn.2012.08.167 · Cited by 112
Thyroid Storm in the ICU: A Retrospective Multicenter Study
Bourcier, S., Coutrot, M., Kimmoun, A., Sonneville, R., de Montmollin, É., Persichini, R., Schnell, D., Charpentier, J., Aubron, C., Morawiec, É., et al. (2019) · Critical Care Medicine · doi:10.1097/ccm.0000000000004078 · Cited by 110
I Diretriz Latino-Americana para avaliação e conduta na insuficiência cardíaca descompensada
Bocchi, E. A., Vilas‐Boas, F., Perrone, S. V., Caamaño, A. G., Clausell, N., Moreira, M. D. C. V., Thierer, J. M., Grancelli, H., Junior, C. V. S., de Albuquerque, D. C., et al. (2005) · Arquivos Brasileiros de Cardiologia · doi:10.1590/s0066-782x2005002200001 · Cited by 115
Ellervik, C., Roselli, C., Christophersen, I. E., Alonso, Á., Pietzner, M., Sitlani, C. M., Trompet, S., Arking, D. E., Geelhoed, B., Guo, X., et al. (2019) · JAMA Cardiology · doi:10.1001/jamacardio.2018.4635 · Cited by 109
Dilated cardiomyopathy and chronic cardiac inflammation: Pathogenesis, diagnosis and therapy
Harding, D., Chong, M. H. A., Lahoti, N., Bigogno, C. M., Prema, R., MOHIDDIN, S. A., & Marelli‐Berg, F. M. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13556 · Cited by 109
Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality
Bano, A., Chaker, L., Mattace-Raso, F. U. S., van der Lugt, A., Ikram, M. A., Franco, O. H., Peeters, R. P., & Kavousi, M. (2017) · Circulation Research · doi:10.1161/circresaha.117.311603 · Cited by 99
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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
Tanabe, N., Iso, H., Seki, N., Suzuki, H., Yatsuya, H., Toyoshima, H., Tamakoshi, A., & for the JACC Study Group (2009) · International Journal of Epidemiology · doi:10.1093/ije/dyp327 · Cited by 97
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Self-citationPotential therapeutic applications of thyroid hormone analogs
Brenta, G., Danzi, S. E., & Klein, I. L. (2007) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0590 · Cited by 100
“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”
BackgroundSelf-citationThyroid Function and Sudden Cardiac Death: A Prospective Population-Based Cohort Study
Chaker, L., van den Berg, M. E., Niemeijer, M. N., Franco, O. H., Dehghan, A., Hofman, A., Rijnbeek, P. R., Deckers, J. W., Eijgelsheim, M., Stricker, B. H. C., et al. (2016) · Circulation · doi:10.1161/circulationaha.115.020789 · Cited by 97
Heart Failure as a Multiple Hormonal Deficiency Syndrome
Saccà, L. (2009) · Circulation Heart Failure · doi:10.1161/circheartfailure.108.821892 · Cited by 94
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Pericardial diseases in patients with hypothyroidism
Chahine, J., Ala, C. K., Gentry, J. L., Pantalone, K. M., & Klein, A. L. (2019) · Heart · doi:10.1136/heartjnl-2018-314528 · Cited by 97
The epidemiology of thyroid diseases in the Arab world: A systematic review
Awad, S. A. S., El‐Metwally, A., Khaled, A. S., Salih, B. S., Yousef, S., Abeer, A. S., & Anna, A. (2016) · Journal of Public Health and Epidemiology · doi:10.5897/jphe2015.0713 · Cited by 93
Lin, Y., & Sun, Z. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01056.x · Cited by 89
Engineered Microenvironments for Maturation of Stem Cell Derived Cardiac Myocytes
Besser, R. R., Ishahak, M., Mayo, V., Carbonero, D., Claure, I., & Agarwal, A. (2017) · Theranostics · doi:10.7150/thno.19441 · Cited by 87
Brandt, F., Almind, D., Christensen, K., Green, A., Brix, T. H., & Hegedüs, L. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2268 · Cited by 83
Moon, J. H., & Yi, K. H. (2013) · Endocrinology and Metabolism · doi:10.3803/enm.2013.28.4.275 · Cited by 79
Thyroid dysfunction in the elderly
Boelaert, K. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.30 · Cited by 84
Thyroid hormone action in postnatal heart development
Li, M., Iismaa, S. E., Naqvi, N., Nicks, A. M., Husain, A., & Graham, R. M. (2014) · Stem Cell Research · doi:10.1016/j.scr.2014.07.001 · Cited by 85
“3) (Klein and Danzi, 2007; Maillet et al., 2013).”
Bhatnagar, D., Kaur, I., & Kumar, A. (2016) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2016.11.037 · Cited by 82
The Role of Thyroid Hormones in Heart Failure
Vale, C., Neves, J. S., von Hafe, M., Borges‐Canha, M., & Leite-Moreira, A. F. (2019) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-019-06870-4 · Cited by 78
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Is subclinical hypothyroidism a cardiovascular risk factor in the elderly?
Pasqualetti, G., Tognini, S., Polini, A., Caraccio, N., & Monzani, F. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3818 · Cited by 79
Thyroid hormones and the cardiovascular system: Pathophysiology and interventions
Cini, G., Carpi, A., Mechanick, J. I., Cini, L., Camici, M., Galetta, F., Giardino, R., Russo, M. A., & Iervasi, G. (2009) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2009.08.003 · Cited by 80
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
Metadata
- 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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