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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Cardiovascular symptoms are the most frequent indicators of mild thyroid hormone excess in the elderly, similar to overt hyperthyroidism.
“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]
The Discussion (p. 3) identifies atrial fibrillation as a manifestation associated with overt hyperthyroidism and finds that low thyrotropin is a risk factor for it in people aged 60 or older. The paper does not establish that cardiovascular symptoms are the most frequent indicators of mild thyroid hormone excess; it defines subclinical hyperthyroidism in an asymptomatic person (p. 1). (LLM, conf=0.88)
Experimental — accuracy not yet measuredAn increased incidence of atrial fibrillation has been observed in elderly persons with low serum TSH (0.1-0.5 mIU/l) with hazard ratios of 1.6 (95% CI 1.0-2.5) and 1.85 (95% CI 1.14-3.00).
“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]
Table 2 (p. 3) reports a relative risk of 1.6 (95% CI 1.0–2.5) for atrial fibrillation in older people with slightly low TSH, supporting the result attached to this citation. Its TSH range is >0.1–0.4 mU/L, not the citing sentence’s 0.1–0.5 mIU/L. The 1.85 estimate is attached to a different citation and is not assessed here. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA 2- to 3-fold increased risk of atrial fibrillation was associated with subclinical hyperthyroidism in elderly subjects in two large prospective studies.
“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]
Excess thyroid hormone can increase the risk of arrhythmias and muscle weakness in older people, which can contribute to a greater risk of falls.
“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]
Lower serum TSH levels are associated with increased risk of atrial fibrillation.
“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]
Older patients with low TSH and higher fT4 have a higher prevalence and incidence of atrial fibrillation compared with euthyroid subjects.
“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]
A low serum TSH level was first associated with an increased risk of atrial fibrillation.
“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 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.
“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]
Many previous studies have shown that low serum TSH is associated with poor outcomes, including increased all-cause or vascular mortality, or atrial fibrillation.
“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]
Sawin et al. first reported a 2.8-fold increased risk of atrial fibrillation in SH subjects over age 60 years in 1994.
“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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Cappola, A. R., Fried, L. P., Arnold, A. M., Danese, M. D., Kuller, L. H., Burke, G. L., Tracy, R. P., & Ladenson, P. W. (2006) · JAMA · doi:10.1001/jama.295.9.1033 · Cited by 862 · see citing works
“5).(12) Individuals with elevated thyroxine levels, indicating overt hyperthyroidism, were included in their category of TSH values of less than 0.”
BackgroundResultRingel, M. D., Sosa, J. A., Baloch, Z. W., Bischoff, L. A., Bloom, G., Brent, G. A., Brock, P. L., Chou, R., Flavell, R. R., Goldner, W. S., et al. (2025) · Thyroid · doi:10.1177/10507256251363120 · Cited by 835 · see citing works
Thyroid Hormone Action in the Heart
Kahaly, G. J., & DILLMANN, W. H. (2005) · Endocrine Reviews · doi:10.1210/er.2003-0033 · Cited by 710 · see citing works
“rather uncommon in the absence of additional symptoms and signs of hyperthyroidism (173).”
BackgroundManagement of Simple Nodular Goiter: Current Status and Future Perspectives
Hegedűs, L. D., Bonnema, S. J., & Bennedbæk, F. N. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0016 · Cited by 707 · see citing works
Gharib, H., Papini, E., Valcavi, R., Baskin, H. J., Crescenzi, A., Dottorini, M. E., Duick, D. S., Guglielmi, R., Hamilton, C. R., Zeiger, M. A., et al. (2006) · Endocrine Practice · doi:10.4158/ep.12.1.63 · Cited by 680 · see citing works
Parle, J. V., Maisonneuve, P., Sheppard, M. C., Boyle, P., & Franklyn, J. A. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06067-6 · Cited by 669 · see citing works
January, C. T., Wann, L. S., Alpert, J. S., Calkins, H. G., Cigarroa, J. E., Cleveland, J. C., CONTI, J. B., Ellinor, P. T., Ezekowitz, M. D., Field, M. E., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.03.021 · Cited by 574 · see citing works
Subclinical hyperthyroidism and the risk of coronary heart disease and mortality
Collet, T.-H., Gussekloo, J., Bauer, D. C., den Elzen, W. P. J., Cappola, A. R., Balmer, P., Iervasi, G., Åsvold, B. O., Sgarbi, J. A., Völzke, H., et al. (2012) · Archives of Internal Medicine · doi:10.1001/archinternmed.2012.402 · Cited by 572 · see citing works
American Thyroid Association guidelines for detection of thyroid dysfunction.
Ladenson, P., Singer, P., Ain, K., Bagchi, N., Bigos, S., Levy, E., Smith, S. A., Daniels, G., & Cohen, H. D. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.11.1573 · Cited by 658 · see citing works
Roberts, C. G., & Ladenson, P. W. (2004) · The Lancet · doi:10.1016/s0140-6736(04)15696-1 · Cited by 567 · see citing works
Patel, K. N., Yip, L., Lubitz, C. C., Grubbs, E. G., Miller, B. S., Shen, W. T., Angelos, P., Chen, H., Doherty, G. M., Fahey, T. J., et al. (2020) · Annals of Surgery · doi:10.1097/sla.0000000000003580 · Cited by 553 · see citing works
Subclinical thyroid dysfunction as a risk factor for cardiovascular disease
Walsh, J. P., Bremner, A. P., Bulsara, M. K., O’Leary, P., Leedman, P. J., Feddema, P., & Michelangeli, V. (2005) · Archives of Internal Medicine · doi:10.1001/archinte.165.21.2467 · Cited by 536 · see citing works
THE EPIDEMIOLOGY OF THYROID DISEASE AND IMPLICATIONS FOR SCREENING
Wang, C., & Crapo, L. M. (1997) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70240-1 · Cited by 520 · see citing works
Gencer, B., Collet, T.-H., Virgini, V., Bauer, D. C., Gussekloo, J., Cappola, A. R., Nanchen, D., den Elzen, W. P. J., Balmer, P., Luben, R. N., et al. (2012) · Circulation · doi:10.1161/circulationaha.112.096024 · Cited by 517 · see citing works
Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death
Rodondi, N., Newman, A. B., Vittinghoff, E., de Rekeneire, N., Satterfield, S., Harris, T. B., & Bauer, D. C. (2005) · Archives of Internal Medicine · doi:10.1001/archinte.165.21.2460 · Cited by 503 · see citing works
“We also performed sensitivity analyses excluding participants who used thyroid hormone, similar to previous studies.(30,31)”
MethodDiagnostic Criteria, Clinical Features, and Incidence of Thyroid Storm Based on Nationwide Surveys
Akamizu, T., Satoh, T., Isozaki, O., Suzuki, A., Wakino, S., Iburi, T., Tsuboi, K., Monden, T., Kouki, T., Otani, H., et al. (2012) · Thyroid® · doi:10.1089/thy.2011.0334 · Cited by 469 · see citing works
“6 (20-80) Male:female 30:76 34:99 74:204 15:59 Basic thyroid diseases Graves’ disease 95.”
Risk for fracture in women with low serum levels of thyroid-stimulating hormone
Bauer, D. C., Ettinger, B., Nevitt, M. C., Stone, K. L., & for the Study of Osteoporotic Fractures Research Group (2001) · Annals of Internal Medicine · doi:10.7326/0003-4819-134-7-200104030-00009 · Cited by 467 · see citing works
“1 mIU/L or less are highly correlated with a diminished response to thyroidreleasing hormone stimulation (33) and are associated with an increased incidence of atrial fibrillation (34).”
BackgroundBjøro, T., Holmen, J., Krüger, Ø., Midthjell, K., Hunstad, K., Schreiner, T., Sandnes, L., & Brochmann, H. (2000) · European Journal of Endocrinology · doi:10.1530/eje.0.1430639 · Cited by 463 · see citing works
“Subclinical hyperthyroidism is a risk factor for atrial fibrillation at least in older persons ( 19 ) and approximately 10‐15% of patients with overt hyperthyroidism, who have atrial fibrillation will have an atrial embolic event (20, 21).”
BackgroundEffects of Thyroid Hormone on the Cardiovascular System
Fazio, S. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.31 · Cited by 445 · see citing works
“About 5–10% of overt hyperthyroid patients have atrial fibrillation, which may be the presenting problem (Sawin et al., 1994; Auer et al., 2001).”
BackgroundBaskin, H. J., Cobin, R. H., Duick, D. S., Gharib, H., Guttler, R. B., Kaplan, M. M., Segal, R. L., Garber, J. R., Hamilton Jr, C. R., Handelsman, Y., et al. (2002) · Endocrine Practice · doi:10.4158/1934-2403-8.6.457 · Cited by 673 · see citing works
Effects of Subclinical Thyroid Dysfunction on the Heart
Biondi, B., Palmieri, E. A., Lombardi, G., & Fazio, S. (2002) · Annals of Internal Medicine · doi:10.7326/0003-4819-137-11-200212030-00011 · Cited by 443 · see citing works
“The prevalence and incidence of atrial fibrillation were higher in patients with subclinical hyperthyroidism 60 years of age or older (82, 99), whereas atrial premature beats were increased in some younger patients (88, 93, 96).”
BackgroundInfluentialThe Evidence for a Narrower Thyrotropin Reference Range Is Compelling
Wartofsky, L., & Dickey, R. A. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0455 · Cited by 424 · see citing works
“As in patients with slightly elevated TSH levels, we are equally concerned about appropriate diagnosis and treatment of patients with TSH levels that are slightly below the reference interval (subclinical hyperthyroidism) because of risks to both heart (51, 52) and bone (53).”
BackgroundIodine-Induced Hyperthyroidism: Occurrence and Epidemiology
STANBURY, J. B., ERMANS, A. E., BOURDOUX, P., TODD, C., OKEN, E., TONGLET, R., VIDOR, G., BRAVERMAN, L. E., & MEDEIROS-NETO, G. (1998) · Thyroid · doi:10.1089/thy.1998.8.83 · Cited by 415 · see citing works
Flynn, R. W., Bonellie, S. R., Jung, R. T., MacDonald, T. M., Morris, A. D., & Leese, G. P. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1625 · Cited by 415 · see citing works
Hypothyroidism as a Risk Factor for Cardiovascular Disease
Biondi, B., & Klein, I. L. (2004) · Endocrine · doi:10.1385/endo:24:1:001 · Cited by 411 · see citing works
Laurberg, P., Pedersen, K. M., Hreiðarsson, Á. B., Sigfússon, N., Iversen, E., & Knudsen, P. R. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.3.4624 · Cited by 399 · see citing works
“The dangers of such a condition are predominantly atrial fibrillation (18) (with a risk of impaired cardiac function and embolism) and osteoporosis (19).”
BackgroundMeier, C., Staub, J.-J., Roth, C.-B., Guglielmetti, M., Kunz, M., Miserez, A. R., Drewe, J., Huber, P., Herzog, R. F. K., & Müller-Stich, B. P. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.10.7973 · Cited by 397 · see citing works
“It has been shown that endogenous SCH may be associated with adverse effects, such as mild clinical signs of hyperthyroidism and impaired quality of life (46), induction of atrial fibrillation (47), acceleration of osteoporosis, or possibly dementia and Alzheimer’s disease (48).”
BackgroundGharib, H., Tuttle, R. M., Baskin, H. J., Fish, L. H., Singer, P. A., & McDermott, M. T. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1231 · Cited by 394 · see citing works
Thyroid Nodules: Clinical Importance, Assessment, and Treatment
Gharib, H., & Papini, E. (2007) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2007.04.009 · Cited by 395 · see citing works
AACE/AAES MEDICAL/SURGICAL Guidelines for Clinical Practice: Management of Thyroid Carcinoma
Cobin, R. H., Gharib, H., Bergman, D. A., Clark, O. H., Cooper, D. S., Daniels, G. H., Dickey, R. A., Duick, D. S., Garber, J. R., HAY, I. D., et al. (2001) · Endocrine Practice · doi:10.4158/ep.7.3.202 · Cited by 366 · see citing works
Status of the Epidemiology of Atrial Fibrillation
Kannel, W. B., & Benjamin, E. J. (2007) · Medical Clinics of North America · doi:10.1016/j.mcna.2007.09.002 · Cited by 359 · see citing works
Cooper, D. S., SPECKER, B. L., Ho, M. L., Sperling, M. I., Ladenson, P. W., Ross, D. S., Ain, K. B., Bigos, S. T., Brierley, J. D., Haugen, B. R., et al. (1998) · Thyroid · doi:10.1089/thy.1998.8.737 · Cited by 352 · see citing works
Mortality in Patients with Pituitary Disease
Sherlock, M., Ayuk, J., Tomlinson, J. W., Toogood, A. A., Aragon-Alonso, A., Sheppard, M. C., Bates, A. S., & Stewart, P. M. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0033 · Cited by 392 · see citing works
Thyroid hormone replacement for subclinical hypothyroidism
Villar, H. C. C. E., Saconato, H., Valente, O., & Atallah, Á. N. (2007) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003419.pub2 · Cited by 329 · see citing works
Selmer, C., Olesen, J. B., Hansen, M. L., Lindhardsen, J., Olsen, A.-M. S., Madsen, J. C., Faber, J., Hansen, P. R., Pedersen, O. D., Torp-Pedersen, C., et al. (2012) · BMJ · doi:10.1136/bmj.e7895 · Cited by 323 · see citing works
Biondi, B., Bartalena, L., Cooper, D. S., Hegedüs, L., Laurberg, P., & Kahaly, G. J. (2015) · European Thyroid Journal · doi:10.1159/000438750 · Cited by 323 · see citing works
Subclinical hyperthyroidism as a risk factor for atrial fibrillation
Auer, J., Scheibner, P., Mische, T., Langsteger, W., Eber, O., & Eber, B. (2001) · American Heart Journal · doi:10.1067/mhj.2001.119370 · Cited by 314 · see citing works
Baek, J. H., Kim, Y. S., Lee, D., Huh, J. Y., & Lee, J. H. (2010) · American Journal of Roentgenology · doi:10.2214/ajr.09.3372 · Cited by 314 · see citing works
“Long-term levothyroxine treatment, however, is contraindicated in many conditions, such as old age, menopause, cardiovascular disease, and osteoporosis [34, 40].”
BackgroundScreening for Thyroid Disease: An Update
Helfand, M., & Redfern, C. C. (1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-129-2-199807150-00020 · Cited by 304 · see citing works
“Fifteen percent to 50% of patients receiving L-thyroxine for primary hypothyroidism are uninten tionally maintained on doses sufficient to cause the TSH level to be undetectable ( 38 , 68, 69).”
InfluentialMolecular Pathogenesis of Euthyroid and Toxic Multinodular Goiter
Krohn, K., Führer, D., Bayer, Y., Eszlinger, M., Brauer, V. F. H., Neumann, S., Paschke, R., & Führer‐Sakel, D. (2004) · Endocrine Reviews · doi:10.1210/er.2004-0005 · Cited by 312 · see citing works
“E-mail: pasr@medizin.uni-leipzig.de This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG/Pa423/3-2 and Pa423/12-1; NE 84417-7, FU 35617- 7), the Krebshilfe (10-1575), and the Interdisziplinäres Zentrum für Klinische Forschung at the Faculty of Medicine of the University of Leipzig (Project…”
BackgroundMethodThe endocrine system and ageing
Chahal, H., & Drake, W. (2007) · The Journal of Pathology · doi:10.1002/path.2110 · Cited by 306 · see citing works
“In older, apparently euthyroid patients, serum thyroid-stimulating hormone (TSH) concentrations may be reduced [55,56], but this is usually a pathological finding indicating either exogenous or endogenous thyrotoxicosis [57].”
BackgroundMortality after the Treatment of Hyperthyroidism with Radioactive Iodine
Franklyn, J. A., Maisonneuve, P., Sheppard, M. C., Betteridge, J., & Boyle, P. (1998) · New England Journal of Medicine · doi:10.1056/nejm199803123381103 · Cited by 308 · see citing works
Environmental Iodine Intake Affects the Type of Nonmalignant Thyroid Disease
Laurberg, P., Pedersen, I. B., Knudsen, N., Ovesen, L., & Andersen, S. (2001) · Thyroid · doi:10.1089/105072501300176417 · Cited by 307 · see citing works
“On the other hand, the population cohort (age, 60–87 years) examined in Framingham, MA, USA, in 1979 (35,36) may have been exposed to a relatively low iodine intake during the early part of their life.”
Helfand, M. (2004) · Annals of Internal Medicine · doi:10.7326/0003-4819-140-2-200401200-00015 · Cited by 302 · see citing works
“Data from the Framingham cohort suggest that 1 excess case of atrial fibrillation might occur for every 114 patients treated with doses of L-thyroxine sufficient to suppress TSH (31).”
BackgroundFox, C. S. (2008) · Archives of Internal Medicine · doi:10.1001/archinte.168.6.587 · Cited by 303 · see citing works
Udovcic, M., Pena, R. H., Patham, B., Tabatabai, L. S., & Kansara, A. (2017) · Methodist DeBakey Cardiovascular Journal · doi:10.14797/mdcj-13-2-55 · Cited by 308 · see citing works
The Thyrotropin Reference Range Should Remain Unchanged
Surks, M. I., Goswami, G., & Daniels, G. H. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0170 · Cited by 287 · see citing works
Biondi, B., & Cooper, D. S. (2010) · Thyroid · doi:10.1089/thy.2009.0311 · Cited by 286 · see citing works
“…considered to be intermediate in the following patient groups: Otherwise healthy patients older than 60 years, because of the potential risk of AF (71,72); Hypertension (108); Increased left ventricular mass or left ventricular hypertrophy (57,59,61,63,64); Diastolic dysfunction (61–63); The…”
Thyroid hormone in health and disease
Boelaert, K., & Franklyn, J. A. (2005) · Journal of Endocrinology · doi:10.1677/joe.1.06131 · Cited by 281 · see citing works
“Nonetheless, these data, together with the AF incidence data evident in the elderly Framingham population (Sawin et al. 1994), have lent support to the view that antithyroid treatment should be considered in those with persistent suppression of TSH and evidence for underlying thyroid disease (thyroid nodular disease o…”
BackgroundResultInfluentialSerum TSH is positively associated with BMI
Nyrnes, A., Jorde, R., & Sundsfjord, J. (2005) · International Journal of Obesity · doi:10.1038/sj.ijo.0803112 · Cited by 274 · see citing works
Franklyn, J. A., & Boelaert, K. (2012) · The Lancet · doi:10.1016/s0140-6736(11)60782-4 · Cited by 262 · see citing works
Treatment with thyroid hormone
Biondi, B., & Wartofsky, L. (2014) · Endocrine Reviews · doi:10.1210/er.2013-1083 · Cited by 259 · see citing works
“The hypermetabolic state associated with undetectable serum TSH can impair psychological, social, and physical QOL and may be associated with the development of some important cardiovascular risk factors (increased heart rate and enhanced risk of atrial arrhythmias, increased left ventricular [L] mass, and diastolic d…”
BackgroundInfluentialThyroid hormone and blood pressure regulation
Danzi, S., & Klein, I. (2003) · Current Hypertension Reports · doi:10.1007/s11906-003-0060-7 · Cited by 261 · see citing works
“In patients older than 60 years of age, there is an increased risk of cardiac arrhythmias, specifically atrial fibrillation [ 75 ].”
BackgroundHoogendoorn, E. H., Hermus, A. R., de Vegt, F., Ross, H. A., Verbeek, A. L., Kiemeney, L. A., Swinkels, D. W., Sweep, F. C., & den Heijer, M. (2006) · Clinical Chemistry · doi:10.1373/clinchem.2005.055194 · Cited by 255 · see citing works
“Subclinical thyrotoxicosis is associated with an increased risk of atrial fibrillation ( 28 ) and osteoporosis (29, 30).”
Continuing Controversies in the Management of Thyroid Nodules
Castro, M. R., & Gharib, H. (2005) · Annals of Internal Medicine · doi:10.7326/0003-4819-142-11-200506070-00011 · Cited by 256 · see citing works
“Because such therapy has been associated with adverse cardiovascular (77) and skeletal effects (78, 79), we advise a careful risk–benefit assessment before recommending this treatment.”
BackgroundMagnani, J. W., Rienstra, M., Lin, H., Sinner, M. F., Lubitz, S. A., McManus, D. D., Dupuis, J., Ellinor, P. T., & Benjamin, E. J. (2011) · Circulation · doi:10.1161/circulationaha.111.039677 · Cited by 247 · see citing works
Baumgartner, C., da Costa, B. R., Collet, T., Feller, M., Floriani, C., Bauer, D. C., Cappola, A. R., Heckbert, S. R., Ceresini, G., Gussekloo, J., et al. (2017) · Circulation · doi:10.1161/circulationaha.117.028753 · Cited by 256 · see citing works
“Additional sensitivity analyses (3) included all individuals regardless of intake of thyroid medication (thyroxine or antithyroid medication), so participants with thyroid medication use at baseline were added to this sensitivity analysis, (4) excluded participants who took amiodarone at baseline (or studies that did…”
BackgroundControversies in primary treatment of low-risk papillary thyroid cancer
McLeod, D. S. A., Sawka, A. M., & Cooper, D. S. (2013) · The Lancet · doi:10.1016/s0140-6736(12)62205-3 · Cited by 246 · see citing works
Epidemiology and significance of atrial fibrillation
Ryder, K. M., & Benjamin, E. J. (1999) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)00713-4 · Cited by 247 · see citing works
Kirchhof, P. F., Lip, G. Y. H., Gelder, I. C. V., Bax, J. J., Hylek, E. M., Kääb, S., Schotten, U., Wegscheider, K., Boriani, G., Brandes, A., et al. (2011) · EP Europace · doi:10.1093/europace/eur241 · Cited by 242 · see citing works
“30 M/F 1.5/1.5 Dublin et al.34 per unit BMI 1.03 Continued . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Table 1 Continued Less validated risk factors and risk markers Hazard ratio Marcus et al.18 – – Cham…”
BackgroundInfluentialSomwaru, L. L., Arnold, A. M., Joshi, N., Fried, L. P., & Cappola, A. R. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1696 · Cited by 239 · see citing works
“The high prevalence of over-replacement (1), and higher thanthe22%prevalencereportedinacommunityhealthfairand the 5% prevalence in a study of an endocrine clinic population (2, 5).”
BackgroundThyroid Diseases and Cerebrovascular Disease
Squizzato, A., Gerdes, V. E. A., Brandjes, D. P. M., Büller, H. R., & Stam, J. (2005) · Stroke · doi:10.1161/01.str.0000181772.78492.07 · Cited by 236 · see citing works
The Treatment of Subclinical Hypothyroidism Is Seldom Necessary
Chu, J. W., & Crapo, L. M. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.10.7961 · Cited by 231 · see citing works
“a thyroid hormone preparation at entry (89).”
Cardiovascular involvement in patients with different causes of hyperthyroidism
Biondi, B., & Kahaly, G. J. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.105 · Cited by 230 · see citing works
Toft, A. D. (2001) · New England Journal of Medicine · doi:10.1056/nejmcp010145 · Cited by 231 · see citing works
Association Between Serum Free Thyroxine Concentration and Atrial Fibrillation
Gammage, M. D. (2007) · Archives of Internal Medicine · doi:10.1001/archinte.167.9.928 · Cited by 225 · see citing works
“5) in those with low but detectable TSH.(7) This cohort was different from the present one in that it included subjects with overt hyperthyroidism and taking thyroid hormones, which may account for the higher prevalence of subclinical thyroid dysfunction than described here.”
Lean Body Mass Is a Major Determinant of Levothyroxine Dosage in the Treatment of Thyroid Diseases
Santini, F., Pinchera, A., Marsili, A., Ceccarini, G., Castagna, M. G., Valeriano, R., Giannetti, M., Taddei, D., Centoni, R., Scartabelli, G., et al. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1306 · Cited by 226 · see citing works
- 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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