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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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“Subclinical hyperthyroidism is generally associated with several clinical conditions, such as atrial fibrillation, cardiac dysfunction, and osteoporosis 5–7 , and can be caused endogenously and exogenously.”
BackgroundAssociation of inflammation with atrial fibrillation in hyperthyroidism
Özaydın, M., Kutlucan, A., Yasin, T., Banu, K., Akif, A., Bayram, A. U., Dogan, E., Ercan, V., & Abdullah, D. (2013) · 老年心脏病学杂志：英文版 · doi:10.3724/sp.j.1263.2012.06251 · Cited by 8
Subclinical Thyroid Dysfunction During Pregnancy
Casey, B. M. (2011) · Clinical Obstetrics & Gynecology · doi:10.1097/grf.0b013e31822e27e3 · Cited by 7
“For example, 1 study in individuals older than 60 years of age found an almost 3-fold increased risk of atrial fibrillation in persons with subclinical hyperthyroidism.(29) Small, uncontrolled studies in similarly aged adults have demonstrated improved cardiac parameters with restoration of a euthyroid state or treatm…”
BackgroundGeng, J., Hu, T., Wang, B., Lu, W., & Ma, S. (2014) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.04.205 · Cited by 8
“Mild thyroid dysfunction is associated with adverse cardiovascular outcomes, including coronary heart disease (CHD) events [1–4], CHD deaths [4–6], heart failure [7,8], and atrial fibrillation (AF) [9–11].”
BackgroundNew Paradigms in the Diagnosis and Management of Thyroid Nodules
Bui, A., & Mazzaferri, E. L. (2007) · The Endocrinologist · doi:10.1097/01.ten.0000257436.13363.b2 · Cited by 8
Muthukumar, S., Ravikumar, K., Dhalapathy, S., Gomathy, T., Umadevi, S., & Maruthupandian, D. (2018) · World Journal of Surgery · doi:10.1007/s00268-018-4571-4 · Cited by 8
Hypothyroidism in Older Adults
Kim, M. I. (2000) · Cited by 8
Yu., A. B., Alekber, A., Elena, N. P., & Eugenia, O. (2012) · InTech eBooks · doi:10.5772/29331 · Cited by 10
Role of Thyroid RFA in the Treatment of Autonomously Functioning Thyroid Nodules
Sag, A. A., Kazaure, H. S., & Kelley, C. E. (2022) · Techniques in vascular and interventional radiology · doi:10.1016/j.tvir.2022.100823 · Cited by 8
Genetic associations with neonatal thyroid-stimulating hormone levels
Alul, F. Y., Shchelochkov, O. A., Berberich, S. L., Murray, J. C., & Ryckman, K. K. (2013) · Pediatric Research · doi:10.1038/pr.2013.18 · Cited by 8
“For example, low serum TSH levels are associated with an increased risk of atrial fibrillation in adults over 60 years old (11).”
BackgroundReverter, J. L., & Colomé, E. (2011) · Endocrinología y Nutrición · doi:10.1016/j.endonu.2010.09.007 · Cited by 8
Goichot, B., & Luca, F. (2011) · La Presse Médicale · doi:10.1016/j.lpm.2011.09.009 · Cited by 8
Transient Hyperthyroidism after Withdrawal of Antithyroid Drugs in Patients with Graves' Disease
Kubota, S., Tamai, H., Ohye, H., Fukata, S., Kuma, K., & Miyauchi, A. (2004) · Endocrine Journal · doi:10.1507/endocrj.51.213 · Cited by 8
The Impact of Age in the Management of Hypothyroidism: Results of a Nationwide Survey
Papaleontiou, M., Gay, B. L., Esfandiari, N. H., Hawley, S. T., & Haymart, M. R. (2016) · Endocrine Practice · doi:10.4158/ep151021.or · Cited by 8
Elevated levels of circulating thyroid hormone do not cause the medical sequelae of hyperthyroidism
Kelly, T., Denmark, L., & Lieberman, D. Z. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.06.001 · Cited by 8
“The authors studied a mixed group of patients with hyperthyroidism and those receiving thyroid hormone therapy (Sawin et al., 1994).”
Subclinical Hypothyroidism: An Overlooked Cause of Atrial Fibrillation?
Kolettis, T. M., & Tsatsoulis, A. A. (2012) · Europe PMC (PubMed Central) · doi:10.4022/jafib.710 · Cited by 8
Díez, J. J. (2005) · Endocrinología y Nutrición · doi:10.1016/s1575-0922(05)71023-8 · Cited by 8
“Se demostró que los sujetos con concentraciones de TSH menores o iguales a 0,1 U/ml presentaban un riesgo 3 veces superior de desarrollar fibrilación auricular en comparación con los sujetos con concentraciones normales de TSH 59 .”
BackgroundBilgir, O., Bilgir, F., Topcuoglu, T., Çalan, M., & Çalan, Ö. G. (2013) · Endocrine · doi:10.1007/s12020-013-9993-z · Cited by 8
Lack of consensus in Europe in the management of nontoxic multinodular goitre
Franklyn, J. A. (2000) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2000.01021.x · Cited by 8
“…the context of nodular goitre (Hermus & Huysmans, 1998), and despite increasing concerns for adverse effects on bone and heart (Faber & Galloe, 1994; Sawin et al., 1994) of subclinical hyperthyroidism, evidence which presumably determines the preference (expressed by nearly 50% of respondents) for…”
BackgroundPostoperative Management of Differentiated Thyroid Cancer
Sabet, A., & Kim, M. (2010) · Otolaryngologic Clinics of North America · doi:10.1016/j.otc.2010.02.003 · Cited by 8
Helfand, M., & Redfern, C. C. (1999) · Annals of Internal Medicine · doi:10.7326/0003-4819-130-2-199901190-00018 · Cited by 8
Sherman, S. I., Cabanillas, M. E., & Lai, S. Y. (2017) · Holland‐Frei Cancer Medicine · doi:10.1002/9781119000822.hfcm081 · Cited by 8
Ji, X., Liang, W., Yu, T., Ding, C., & Lv, B. (2024) · Surgery · doi:10.1016/j.surg.2024.109028 · Cited by 7
A comparative analysis of treatment efficacy in intermediate-risk thyroid cancer
Abiri, A., Nguyen, T. T., Goshtasbi, K., Torabi, S. J., Kuan, E. C., Armstrong, W. B., Tjoa, T., & Haidar, Y. M. (2023) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-023-07832-1 · Cited by 7
“However, other studies have shown no difference in outcomes in those that receive THST in low- and intermediate-risk DTC, but rather increased incidence of adverse effects such as atrial fibrillation and osteoporosis [11, 12].”
ResultLiu, X., Wong, C. K. H., Wu, T., Chan, W., Woo, Y. C., Lam, C. L. K., & Lang, B. H. (2024) · World Journal of Surgery · doi:10.1002/wjs.12066 · Cited by 7
Chronic fatigue: is it endocrinology?
Evans, K. M., Flanagan, D., & Wilkin, T. J. (2009) · Clinical Medicine · doi:10.7861/clinmedicine.9-1-34 · Cited by 7
2014 Indonesian Heart Association Guidelines of Management of Atrial Fibrillation
Yuniadi, Y., Hanafy, D. A., Rahardjo, S. B., Tondas, A. E., Maharani, E., Hermanto, D. Y., & Munawar, M. (2015) · Indonesian Journal of Cardiology · doi:10.30701/ijc.v35i2.398 · Cited by 7
Subclinical Hyperthyroidism and Cardiovascular Risk
Palmeiro, C., Davila, M. I., Bhat, M., Frishman, W. H., & Weiss, I. A. (2013) · Cardiology in Review · doi:10.1097/crd.0b013e318294f6f1 · Cited by 7
Brusseau, V., Tauveron, I., Bagheri, R., Ugbolue, U. C., Magnon, V., Bouillon‐Minois, J., Navel, V., & Dutheil, F. (2022) · Biomedicines · doi:10.3390/biomedicines10081982 · Cited by 8
“The majority of subclinical hyperthyroidism does not progress to overt hyperthyroidism [81], but there is still a risk factor for arrhythmia by atrial fibrillation, and it is associated with excess cardiac mortality [3].”
BackgroundInfluentialIssa, P. P., Hussein, M. H., Omar, M., Munshi, R., Attia, A. S., Buti, Y. J., Aboueisha, M. A., Shama, M., Toraih, E. A., & Kandil, E. H. (2022) · Journal of Surgical Research · doi:10.1016/j.jss.2022.10.043 · Cited by 7
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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