The Association of Thyroid Dysfunction with All-Cause and Circulatory Mortality: Is There a Causal Relationship?

Völzke, Henry; Schwahn, Christian; Wallaschofski, Henri; Dörr, Marcus

doi:10.1210/jc.2007-0179

Cited by 120Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

The Association of Thyroid Dysfunction with All-Cause and Circulatory Mortality: Is There a Causal Relationship?

Völzke, Henry, Schwahn, Christian, Wallaschofski, Henri, Dörr, Marcus·2007·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2007-0179

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Abstract

CONTEXT: Currently there is ongoing debate on whether subclinical and overt thyroid dysfunction may exert deleterious effects on the cardiovascular system with the consequence of increased mortality in affected individuals. We systematically review studies on the relation of thyroid dysfunction with all-cause and circulatory mortality questioning whether thyroid dysfunction is a causal factor for mortality. METHODS: Two investigators independently searched the MEDLINE database. All case-control and cohort studies published in peer-reviewed journals were selected. Studies on nonthyroidal illness or low-T3 syndrome and reports from highly selected populations were not considered. Risk estimates from studies with appropriate adjustment for confounders were metaanalyzed. RESULTS: Four among eight studies performed to investigate the association between hyperthyroidism and mortality revealed an increased risk of either all-cause or circulatory mortality. Only the minority of studies, however, adjusted analyses for relevant confounders besides age, sex, and race. Studies after radioiodine therapy were generally biased by indication. Findings from 11 studies that investigated the relation between hypothyroidism and mortality were highly discrepant and partly even mutually exclusive. Some of these discrepancies are explained by confounding and selection. CONCLUSIONS: The currently available evidence for a causal relation of both hyperthyroidism and hypothyroidism with mortality is weak and should particularly not be used to decide whether patients with subclinical thyroid conditions should be treated. Very old individuals might represent an exception from this rule and may benefit from mildly reduced thyroid function, but this has to be substantiated by further research.

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Two meta-analyses did not find a link between subclinical hyperthyroidism and mortality.
“Two did not find a link between SHyper and mortality [89,90] , whereas four other meta-analyses found an association between SHyper and cardiovascular or all-cause mortality [71,[91][92][93] , especially in elderly patients and in patients with co-morbidities [91,92] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [89]

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The Clinical Significance of Subclinical Thyroid Dysfunction
Biondi, B., & Cooper, D. S. (2008) · Endocrine Reviews · doi:10.1210/er.2006-0043 · Cited by 1,418 · see citing works
Subclinical Hypothyroidism and the Risk of Coronary Heart Disease and Mortality
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The Influence of Age on the Relationship between Subclinical Hypothyroidism and Ischemic Heart Disease: A Metaanalysis
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Subclinical Hypothyroidism Is Associated With Increased Risk for All-Cause and Cardiovascular Mortality in Adults
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A high normal TSH is associated with the metabolic syndrome
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Subclinical Thyroid Dysfunction and the Risk of Heart Failure in Older Persons at High Cardiovascular Risk
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The Natural History of Subclinical Hypothyroidism in the Elderly: The Cardiovascular Health Study
Somwaru, L. L., Rariy, C. M., Arnold, A. M., & Cappola, A. R. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3047 · Cited by 210 · see citing works
Older Subjects with Hyperthyroidism Present with a Paucity of Symptoms and Signs: A Large Cross-Sectional Study
Boelaert, K., Torlinska, B., Holder, R. L., & Franklyn, J. A. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2495 · Cited by 196 · see citing works
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Haentjens, P., Van Meerhaeghe, A., Poppe, K., & Velkeniers, B. (2008) · European Journal of Endocrinology · doi:10.1530/eje-08-0110 · Cited by 174 · see citing works
A critical review and meta-analysis of the association between overt hyperthyroidism and mortality
Brandt, F., Green, A., Hegedüs, L., & Brix, T. H. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0299 · Cited by 170 · see citing works
Initial thyroid status and cardiovascular risk factors: The EPIC‐Norfolk prospective population study
Boekholdt, S. M., Titan, S. M., Wiersinga, W. M., Chatterjee, K., Basart, D. C. G., Luben, R., Wareham, N. J., & Khaw, K. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03640.x · Cited by 167 · see citing works
Endogenous subclinical thyroid disorders, physical and cognitive function, depression, and mortality in older individuals
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Hypothyroidism and Moderate Subclinical Hypothyroidism Are Associated with Increased All-Cause Mortality Independent of Coronary Heart Disease Risk Factors: A PreCIS Database Study
McQuade, C., Skugor, M., Brennan, D. M., Hoar, B. M., Stevenson, C., & Hoogwerf, B. J. (2011) · Thyroid · doi:10.1089/thy.2010.0298 · Cited by 152 · see citing works
Subclinical thyroid dysfunctions are independent risk factors for mortality in a 7.5-year follow-up: the Japanese–Brazilian thyroid study
Sgarbi, J. A., Matsumura, L. K., Kasamatsu, T. S., Ferreira, S. R. G., & Maciel, R. M. B. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0845 · Cited by 138 · see citing works
State of the art paper Hyperthyroidism and cardiovascular complications: a narrative review on the basis of pathophysiology
Ertek, S., & Cicero, A. F. G. (2013) · Archives of Medical Science · doi:10.5114/aoms.2013.38685 · Cited by 131 · see citing works
Update in Testosterone Therapy for Men (CME)
Corona, G., Rastrelli, G., Forti, G., & Maggi, M. (2011) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2010.02200.x · Cited by 124 · see citing works
Hyperthyroidism and Risk of Ischemic Stroke in Young Adults: A 5-Year Follow-Up Study
Sheu, J.-J., Kang, J.-H., Lin, H.-C., & Lin, H.-C. (2010) · Stroke · doi:10.1161/strokeaha.109.577742 · Cited by 104 · see citing works
Complex relationship between free thyroxine and TSH in the regulation of thyroid function
Hoermann, R., Eckl, W., Hoermann, C., & Larisch, R. (2010) · European Journal of Endocrinology · doi:10.1530/eje-10-0106 · Cited by 101 · see citing works
Clinical outcomes after estimated versus calculated activity of radioiodine for the treatment of hyperthyroidism: systematic review and meta-analysis
de Rooij, A., Vandenbroucke, J. P., Smit, J. W. A., Stokkel, M. P. M., & Dekkers, O. M. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0286 · Cited by 102 · see citing works
Natural history of subclinical hyperthyroidism in elderly patients with TSH between 0·1 and 0·4 mIU/l: a prospective study
Rosario, P. W. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03696.x · Cited by 88 · see citing works
Thyroid Function and Lipid Subparticle Sizes in Patients with Short-Term Hypothyroidism and a Population-Based Cohort
Pearce, E. N., Wilson, P. W. F., Yang, Q., Vasan, R. S., & Braverman, L. E. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1987 · Cited by 85 · see citing works
Graves' Disease and Toxic Nodular Goiter Are Both Associated with Increased Mortality But Differ with Respect to the Cause of Death: A Danish Population-Based Register Study
Brandt, F., Thvilum, M., Almind, D., Christensen, K., Green, A., Hegedüs, L., & Brix, T. H. (2013) · Thyroid · doi:10.1089/thy.2012.0500 · Cited by 86 · see citing works
Thyroid dysfunction in the elderly
Boelaert, K. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.30 · Cited by 84 · see citing works
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 77 · see citing works
A review of the evidence for and against increased mortality in hypothyroidism
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Thyroid Function Changes in the Elderly and Their Relationship to Cardiovascular Health: A Mini-Review
Barbesino, G. (2018) · Gerontology · doi:10.1159/000490911 · Cited by 73 · see citing works
Duration of Thyroid Dysfunction Correlates with All-Cause Mortality. The OPENTHYRO Register Cohort
Laulund, A. S., Nybo, M., Brix, T. H., Abrahamsen, B., Jørgensen, H. L., & Hegedüs, L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0110437 · Cited by 70 · see citing works
Prognostic impact of subclinical thyroid dysfunction in heart failure
Frey, A., Kroiß, M., Berliner, D., Seifert, M., Allolio, B., Güder, G., Ertl, G., Angermann, C. E., Störk, S., & Faßnacht, M. (2012) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.09.064 · Cited by 68 · see citing works
Decreased serum TSH levels are not associated with mortality in the adult northeast German population
Ittermann, T., Haring, R., Sauer, S., Wallaschofski, H., Dörr, M., Nauck, M. A., & Völzke, H. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0566 · Cited by 68 · see citing works
Self-citation
Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?
Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2013) · European Journal of Endocrinology · doi:10.1530/eje-12-0819 · Cited by 59 · see citing works
Thyroid gland dysfunction and its effect on the cardiovascular system: a comprehensive review of the literature
Ahmadi, N., Ahmadi, F., Sadiqi, M., Ziemnicka, K., & Mińczykowski, A. (2020) · Endokrynologia Polska · doi:10.5603/ep.a2020.0052 · Cited by 58 · see citing works
Consenso brasileiro para a abordagem clínica e tratamento do hipotireoidismo subclínico em adultos: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia
Sgarbi, J. A., Teixeira, P. D. F. D. S., Maciel, L. M. Z., Mazeto, G. M. F. D. S., Vaisman, M., Montenegro, R. M., & Ward, L. S. (2013) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302013000300003 · Cited by 56 · see citing works
Subclinical Hyperthyroidism and the Cardiovascular Disease
Delitala, A. (2017) · Hormone and Metabolic Research · doi:10.1055/s-0043-117893 · Cited by 51 · see citing works
Body Mass Index Regulates Hypogonadism-Associated CV Risk: Results from a Cohort of Subjects with Erectile Dysfunction
Corona, G., Rastrelli, G., Monami, M., Melani, C., Balzi, D., Sforza, A., Forti, G., Mannucci, E., & Maggi, M. (2011) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2011.02292.x · Cited by 51 · see citing works
MANAGEMENT OF ENDOCRINE DISEASE: Subclinical thyrotoxicosis: prevalence, causes and choice of therapy
Carlé, A., Andersen, S. L., Boelaert, K., & Laurberg, P. (2017) · European Journal of Endocrinology · doi:10.1530/eje-16-0276 · Cited by 48 · see citing works
An Analysis of the Natural Course of Subclinical Hyperthyroidism
Díez, J. J., & Iglesias, P. (2009) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e318187e16d · Cited by 45 · see citing works
Prognostic Role of Hypothyroidism in Heart Failure
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Thyroid Hormone Profile in Patients With Acute Coronary Syndrome
Qari, F. A. (2015) · Iranian Red Crescent Medical Journal · doi:10.5812/ircmj.26919v2 · Cited by 36 · see citing works
Higher Serum Free Thyroxine Levels Are Associated with Coronary Artery Disease
Jung, C., Rhee, E., Shin, H. S., Jo, S.-K., Won, J. C., Park, C. ‐., Kim, B. J., Sung, K., Bum-Soo, K. I. M., Lee, W., et al. (2008) · Endocrine Journal · doi:10.1507/endocrj.k08e-010 · Cited by 36 · see citing works
Subclinical hyperthyroidism is not associated with progression of cardiac mass and development of left ventricular hypertrophy in middle‐aged and older subjects: results from a 5‐year follow‐up
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Self-citation
How could we improve the increased cardiovascular mortality in patients with overt and subclinical hyperthyroidism?
Biondi, B. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0585 · Cited by 32 · see citing works
Normal flow-mediated vasodilatation of the brachial artery and carotid artery intima-media thickness in subclinical hypothyroidism
Cabral, M. D., Teixeira, P. D. F. D. S., Silva, N. A. O., de Morais, F. F. C., Soares, D. V., Salles, E. F., Henriques, J. M., Leite, S. P., Montenegro, C. A. B., & Vaisman, M. (2009) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2009000500005 · Cited by 33 · see citing works
TSH Measurement and Its Implications for Personalised Clinical Decision-Making
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Associations between thyroid function and mortality: the influence of age
van de Ven, A. C., Netea-Maier, R. T., de Vegt, F., Ross, H. A., Sweep, F. C. G. J., Kiemeney, L. A., Smit, J. W., Hermus, A. R., & den Heijer, M. (2014) · European Journal of Endocrinology · doi:10.1530/eje-13-1070 · Cited by 31 · see citing works
Incremental Effects of Endocrine and Metabolic Biomarkers and Abdominal Obesity on Cardiovascular Mortality Prediction
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The Prevalence and Prognostic Effects of Subclinical Thyroid Dysfunction in Dilated Cardiomyopathy Patients: A Single-Center Cohort Study
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Should we treat mild subclinical/mild hyperthyroidism? Yes
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Should we treat all subjects with subclinical thyroid disease the same way?
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Serum T3 Level Can Predict Cardiovascular Events and All-Cause Mortality Rates in CKD Patients with Proteinuria
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Mild Hypothyroidism and Ischemic Heart Disease: Is Age the Answer?
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Increased reverse triiodothyronine is associated with shorter survival in independently-living elderly: the Alsanut study
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Thyroid Disorders and Prognosis in Chronic Heart Failure: A Long-Term Follow-Up Study
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Underestimation of Effect of Thyroid Function Parameters on Morbidity and Mortality due to Intra-Individual Variation
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Subclinical hyperthyroidism increases risk of coronary heart disease events in type 2 diabetes mellitus
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Thyroid dysfunction and cardiovascular risk factors in Bulgarian adults
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Authors: Völzke, H., Schwahn, C., Wallaschofski, H., & Dörr, M.
Affiliations: Institute of Epidemiology and Social Medicine (H.V., C.S.), University of Greifswald, D-17487 Greifswald, Germany
Universität Greifswald (DE)
Departments of Cardiology (M.D.), University of Greifswald, D-17487 Greifswald, Germany
ORCID: Schwahn, Christian
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2007-07-01
Volume: 92
Issue: 7
Pages: 2421-2429
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2007-0179
OpenAlex: W2114636478
Cited by: 120
References: 81
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 6 · 2019: 2 · 2018: 1 · 2017: 2 · 2015: 10 · 2014: 11 · 2013: 11 · 2012: 17
FWCI: 2.02
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords: thyroid dysfunction, hyperthyroidism, hypothyroidism, subclinical thyroid dysfunction, all-cause mortality, circulatory disease mortality, cardiovascular mortality, radioiodine therapy, confounding, selection bias, causal relationship, elderly patients
MeSH terms: Cardiovascular Diseases, Cause of Death, Humans, Hyperthyroidism, Risk Factors

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The Association of Thyroid Dysfunction with All-Cause and Circulatory Mortality: Is There a Causal Relationship?

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