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Low Serum Thyrotropin Concentrations as a Risk Factor for Atrial Fibrillation in Older Persons
Open accessAbstract
BACKGROUND: Low serum thyrotropin concentrations are a sensitive indicator of hyperthyroidism but can also occur in persons who have no clinical manifestations of the disorder. We studied whether low serum thyrotropin concentrations in clinically euthyroid older persons are a risk factor for subsequent atrial fibrillation. METHODS: We studied 2007 persons (814 men and 1193 women) 60 years of age or older who did not have atrial fibrillation in order to determine the frequency of this arrhythmia during a 10-year follow-up period. The subjects were classified according to their serum thyrotropin concentrations: those with low values (< or = 0.1 mU per liter; 61 subjects); those with slightly low values (> 0.1 to 0.4 mU per liter; 187 subjects); those with normal values (> 0.4 to 5.0 mU per liter; 1576 subjects); and those with high values (> 5.0 mU per liter; 183 subjects). RESULTS: During the 10-year follow-up period, atrial fibrillation occurred in 13 persons with low initial values for serum thyrotropin, 23 with slightly low values, 133 with normal values, and 23 with high values. The cumulative incidence of atrial fibrillation at 10 years was 28 percent among the subjects with low serum thyrotropin values (< or = 0.1 mU per liter), as compared with 11 percent among those with normal values; the age-adjusted incidence of atrial fibrillation was 28 per 1000 person-years among those with low values and 10 per 1000 person-years among those with normal values (P = 0.005). After adjustment for other known risk factors, the relative risk of atrial fibrillation in elderly subjects with low serum thyrotropin concentrations, as compared with those with normal concentrations, was 3.1 (95 percent confidence interval, 1.7 to 5.5; P < 0.001). The 10-year incidence of atrial fibrillation in the groups with slightly low and high serum thyrotropin values was not significantly different from that in the group with normal values. CONCLUSIONS: Among people 60 years of age or older, a low serum thyrotropin concentration is associated with a threefold higher risk that atrial fibrillation will develop in the subsequent decade.
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In the citing paper
“Cardiovascular symptoms are the most frequent indicators of mild thyroid hormone excess in the elderly, similar to overt hyperthyroidism [52,53] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [52]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“An increased incidence of AF has also been observed in elderly persons with low serum TSH (0.1-0.5 mIU/l) with an HR of 1.6 (95% CI: 1.0-2.5)[52] and 1.85 (95% CI: 1.14-3.00)[53] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [52]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“A 2-to 3-fold increased risk of atrial fibrillation (AF) was associated with SHyper in elderly subjects in two large prospective studies [52,53] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [52]
The cited source says what the claim attributes to it.
In the citing paper
“Excess thyroid hormone can also increase the risk of arrhythmias24 25 and muscle weakness23 in older people, which can contribute to a greater risk of falls.”
From Levothyroxine dose and risk of fractures in older adults: nested case-control study (2011) · cites this paper as [24]
The cited source says what the claim attributes to it.
In the citing paper
“lower serum TSH levels are associated with increased risk of atrial fibrillation (AF) (60)”
From Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism (2020) · cites this paper as [60]
In the citing paper
“Older patients with low TSH and higher fT4 have a higher prevalence and incidence of atrial fibrillation compared with euthyroid subjects (94–98)”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [97]
In the citing paper
“Twenty years ago, a low serum TSH level was first associated with an increased risk of atrial fibrillation (AF) (12)”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [12]
In the citing paper
“in cohort studies, subclinical hyperthyroidism or lower serum TSH have been associated with many involutional disease states including dementia, osteoporosis, AF, muscle weakness, low bone density, and fracture (12–14, 18, 20, 48, 49).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [12]
In the citing paper
“In contrast with subclinical hypothyroidism, many previous studies have shown that low serum TSH is associated with poor outcomes, either increased all-cause or vascular mortality, or AF (12–14, 17, 29, 36, 37).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [12]
In the citing paper
“Sawin et al. (399) first reported a 2.8-fold increased risk of atrial fibrillation in SH subjects over age 60 years in 1994, and subsequent studies have confirmed that the risk of arrhythmias, particularly atrial fibrillation, is increased in SH (381,384,388,391,400,401).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [399]
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“7 Some studies have demonstrated that elderly women who suffer from subclinical hypothyroidism are at an increased risk for atherosclerosis and myocardial infarction(38); subclinical hyperthyroidism is a risk factor for atrial fibrillation in elderly populations.(39) Therefore, we suggest that elderly populations with…”
BackgroundThyroid Hormone Replacement in Patients Following Thyroidectomy for Thyroid Cancer
Hannoush, Z. C., & Weiss, R. E. (2016) · Rambam Maimonides Medical Journal · doi:10.5041/rmmj.10229 · Cited by 30
Diagnosing and Managing Thyroid Disease in the Nursing Home
Dominguez, L. J., Bevilacqua, M. T., Bella, G. D., & Barbagallo, M. (2008) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2007.07.011 · Cited by 26
Roh, E., Noh, E., Hwang, S. Y., Kim, J. A., Song, E., Park, M., Choi, K. M., Baik, S. H., Cho, G. J., & Yoo, H. J. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab776 · Cited by 26
Should we treat mild subclinical/mild hyperthyroidism? No
Vanderpump, M. P. J. (2011) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2011.03.009 · Cited by 25
“Data from the Framingham cohort suggest that 1 excess case of atrial fibrillation might occur for every 114 patients treated with doses of levothyroxine sufficient to suppress the serum TSH [20].”
BackgroundXia, Q., Dong, S., Bian, P., Wang, J., & Li, C. (2015) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-015-3564-2 · Cited by 25
Jorde, R., Joakimsen, O., Stensland, E., & Mathiesen, E. B. (2007) · Thyroid · doi:10.1089/thy.2007.0165 · Cited by 25
Carlos-Raboca, J., Jimeno, C., Kho, S., Andag‐Silva, A., Jasul, G., Nicodemus, N. A., Cunanan, E. C., & Duante, C. A. (2012) · Journal of the ASEAN Federation of Endocrine Societies · doi:10.15605/jafes.027.01.04 · Cited by 25
Risk-benefit ratio for TSH- suppressive Levothyroxine therapy in differentiated thyroid cancer
Cao, C. D., & Wémeau, J.-L. (2015) · Annales d Endocrinologie · doi:10.1016/s0003-4266(16)30014-2 · Cited by 25
Case finding and screening strategies for thyroid dysfunction
Stockigt, J. (2002) · Clinica Chimica Acta · doi:10.1016/s0009-8981(01)00715-x · Cited by 26
Subclinical hyperthyroidism: to treat or not to treat?
Hoogendoorn, E. H., den Heijer, M., van Dijk, A. P. J., & Hermus, A. R. M. M. (2004) · Postgraduate Medical Journal · doi:10.1136/pgmj.2003.017095 · Cited by 25
“Researchers from the Framingham Heart Study followed 2007 subjects over 60 years of age for 10 years.”
MethodThoughts on Prevention of Thyroid Disease in the United States
Cooper, D. S., & Ridgway, E. C. (2002) · Thyroid · doi:10.1089/105072502761016566 · Cited by 24
“In the report by Sawin et al (18), the risk of atrial fibrillation in individuals with serum TSH less than 0.1 mU/L was approximately 28% over 10 years, a value that was approximately three times higher than that observed in individuals with normal or elevated serum TSH.”
InfluentialThyroxine Therapy in Euthyroid Patients Does Not Affect Body Composition or Muscular Function
Dubois, S., Abraham, P., Rohmer, V., Rodien, P., Audran, M., Dumas, J.-F., & Ritz, P. (2008) · Thyroid · doi:10.1089/thy.2007.0037 · Cited by 24
Neves, J. S., Fontes‐Carvalho, R., Borges‐Canha, M., Leite, A. R., Martins, S., Oliveira, A. B. F. D., Guimarães, J. T., Carvalho, D. M., Leite-Moreira, A. F., & Azevedo, A. (2020) · European Thyroid Journal · doi:10.1159/000508407 · Cited by 26
“Furthermore, subclinical hyperthyroidism has been associated with an increased incidence of cardiac arrhythmias, particularly atrial fibrillation [15, 16], and subclinical hypo-thyroidism has been linked to an increased risk of hypertension [17, 18].”
BackgroundHennessey, J. V., Garber, J. R., Woeber, K. A., Cobin, R. H., & Klein, I. L. (2016) · Endocrine Practice · doi:10.4158/ep151038.ps · Cited by 24
Bonelli, N., Rossetto, R., Castagno, D., Anselmino, M., Vignolo, F., Parasiliti‐Caprino, M., Gaïta, F., Ghigo, E., Garberoglio, R., Grimaldi, R., et al. (2017) · Clinical Endocrinology · doi:10.1111/cen.13494 · Cited by 25
Bjørndal, M. M., Wilhelmsen, K. S., Lu, T., & Jorde, R. (2008) · Journal of Endocrinological Investigation · doi:10.1007/bf03346431 · Cited by 23
Da Conceição, R. R., Fernandes, G. W., Fonseca, T. L., Bocco, B. M. L. C., & Bianco, A. C. (2018) · Thyroid · doi:10.1089/thy.2018.0205 · Cited by 23
“Long-term studies indicate that having even minimally elevated thyroid hormone levels places patients at a significantly greater risk for cardiovascular events (17,18) and hip fractures (19).”
Iglesias, P., Ridruejo, E., Muñoz, A., Prado, F., Macías, M. C., Guerrero, M. T., Tajada, P., García-Arévalo, C., & Díez, J. J. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3849 · Cited by 23
Differences in Heart Rate Profile During Exercise Among Subjects with Subclinical Thyroid Disease
Maor, E., Kivity, S., Kopel, E., Segev, S., Sidi, Y., Goldenberg, I., & Olchovsky, D. (2013) · Thyroid · doi:10.1089/thy.2013.0043 · Cited by 22
Asymptomatic Hyperthyroidism in Older Adults
Mooradian, A. D. (2008) · Drugs & Aging · doi:10.2165/00002512-200825050-00002 · Cited by 23
Thyroid lobectomy for indeterminate FNA: not without consequences
Balentine, C. J., Domingo, R. P., Patel, R. R., Laucirica, R., & Suliburk, J. W. (2013) · Journal of Surgical Research · doi:10.1016/j.jss.2013.05.076 · Cited by 23
“[7] Sawin CT, Geller A, Wolf PA, et al.”
BackgroundExercise Performance in Young and Middle-Aged Female Patients with Subclinical Hyperthyroidism
Portella, R. B., Silva, J. L. D. C., Wagman, M. B., de Oliveira, F. P., Buescu, A., & Vaisman, M. (2006) · Thyroid · doi:10.1089/thy.2006.16.731 · Cited by 23
“Age and BMI can influence the exercise test, as can the degree of TSH suppression, but a multivariate analysis was pre-cluded because of the small sample.”
InfluentialGalloway, A., Li, H., Vanderlinde‐Wood, M., Khan, M., Benbrook, A., Liles, C., Zillner, C., Rao, V., Cunningham, M. W., Yu, X., et al. (2014) · Endocrine · doi:10.1007/s12020-014-0495-4 · Cited by 23
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“Previous observations suggested that SHT could exert many significant effects on the cardiovascular system [25,26].”
BackgroundSympathovagal response to orthostatism in overt and in subclinical hyperthyroidism
Goichot, B., BRANDENBERGER, G., Vinzio, S., Perrin, A., Gény, B., Schlienger, J.-L., & Simon, C. (2004) · Journal of Endocrinological Investigation · doi:10.1007/bf03351060 · Cited by 23
Griebeler, M. L., & Gharib, H. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8684-8_4 · Cited by 23
Fortnightly review: Controversial aspects of thyroid disease
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Klein, I. L., & Danzi, S. E. (2003) · Thyroid · doi:10.1089/10507250360731523 · Cited by 23
“These changes in serum TSH both increased and decreased, in turn, can correlate with atrial fibrillation (3).”
InfluentialAronow, W. S. (1999) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1999.tb01602.x · Cited by 23
Challenges in the Management of Atrial Fibrillation With Subclinical Hyperthyroidism
Gencer, B., Cappola, A. R., Rodondi, N., & Collet, T. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.795492 · Cited by 22
“8-fold increased risk of AF among patients with subclinical hyperthyroidism compared to patients with euthyroidism (8, 9, 21).”
BackgroundSanyal, D., Ray, S., & Malhi, H. S. (2022) · Endocrine Regulations · doi:10.2478/enr-2022-0033 · Cited by 27
Goichot, B., Sapin, R., & Schlienger, J. L. (2009) · Clinical Chemistry · doi:10.1373/clinchem.2008.110627 · Cited by 22
“(9) first reported an association between an increased risk of atrial fibrillation (AF) and low TSH concentrations for individuals in the Framingham cohort.”
BackgroundThe value of red blood cell distribution width in subclinical hypothyroidism
Yu, H. M., Park, K. S., & Lee, J. M. (2014) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/0004-2730000002836 · Cited by 20
Endocrine Complications of Surgical Treatment of Thyroid Cancer: An Update
Iglesias, P., & Díez, J. J. (2017) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-0043-106441 · Cited by 22
Metadata
- Authors
- Sawin, C. T., Geller, A., Wolf, P. A., Belanger, A. J., Baker, E., Bacharach, P., Wilson, P., Benjamin, E. J., & D'Agostino, R. B.
- Affiliations
- Boston University (US)
- Veterans Health Administration (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1994-11-10
- Volume
- 331
- Issue
- 19
- Pages
- 1249-1252
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2335515807
- Cited by
- 1,259
- References
- 31
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 27 · 2023: 25 · 2022: 46 · 2021: 37 · 2020: 27 · 2019: 38 · 2018: 41 · 2017: 44 · 2016: 48 · 2015: 45 · 2014: 44 · 2013: 63 · 2012: 65
- FWCI
- 16.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (n01hc038038-022, 5r01hl040423-06)
- National Heart, Lung, and Blood Institute (R01-HL-40423-04, N01-HC-38038)
- National Institute of Neurological Disorders and Stroke (2-R01-NS-17950-12, R01NS017950)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- thyroid-stimulating hormone, subclinical hyperthyroidism, older adults, hyperthyroidism, arrhythmia risk, thyroid function, incidence, risk factors, euthyroid patients, parathyroid hormone, parathyroidectomy, parathyroid hormone replacement, hypoparathyroidism
- MeSH terms
- Age Factors, Aged, Atrial Fibrillation, Female, Follow-Up Studies, Humans, Hyperthyroidism, Male, Middle Aged, Risk Factors, Thyrotropin, Thyroxine, Incidence, Confidence Intervals
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