Thyroid Hormone Therapy and Incident Stroke
Open accessAbstract
CONTEXT: Stroke is a leading cause of death and disability and there is a need to identify modifiable risk factors. OBJECTIVE: We aimed to determine the relationship between thyroid hormone treatment intensity and incidence of atrial fibrillation and stroke. METHODS: We conducted a retrospective cohort study using data from the Veterans Health Administration between 2004 and 2017, with a median follow-up of 59 months. The study population comprised 733 208 thyroid hormone users aged ≥18 years with at least 2 thyroid stimulating hormone (TSH) measurements between thyroid hormone initiation and incident event (atrial fibrillation or stroke) or study conclusion (406 030 thyroid hormone users with at least 2 free thyroxine [T4] measurements). RESULTS: Overall, 71 333/643 687 (11.08%) participants developed incident atrial fibrillation and 41 931/663 809 (6.32%) stroke. In multivariable analyses controlling for pertinent factors such as age, sex, and prior history of atrial fibrillation, higher incidence of stroke was associated with low TSH or high free T4 levels (ie, exogenous hyperthyroidism; eg, TSH <0.1 mIU/L; OR 1.33; 95% CI, 1.24-1.43; free T4>1.9 ng/dL, OR 1.17, 95% CI 1.06-1.30) and high TSH or low free T4 levels (ie, exogenous hypothyroidism; eg, TSH >5.5 mIU/L; OR 1.29; 95% CI, 1.26-1.33; free T4 <0.7 ng/dL; OR 1.29; 95% CI, 1.22-1.35) compared with euthyroidism (TSH >0.5-5.5 mIU/L and free T4 0.7-1.9 ng/dL). Risk of developing atrial fibrillation and stroke was cumulative over time for both patients with exogenous hyperthyroidism and hypothyroidism. CONCLUSION: Both exogenous hyper- and hypothyroidism were associated with increased risk of stroke, highlighting the importance of patient medication safety.
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In younger individuals, increased risks of adverse outcomes were observed in patients with TSH concentrations less than 0.1 mIU/L (but not 0.1-0.4 mIU/L), in terms of all-cause mortality, atrial fibrillation, and stroke risk.
“In younger individuals, increased risks of adverse outcomes were observed in patients with TSH concentrations less than 0•1 mIU/L (but not 0•1-0•4 mIU/L), in terms of all-cause mortality, 160 atrial fibrillation, and stroke risk.161”
From Hypothyroidism (2024) · cites this paper as [161]
The Results (page unavailable) associate TSH <0.1 mIU/L with higher incidence of atrial fibrillation and stroke. The paper studies adult thyroid-hormone users, however, and does not establish that finding specifically in younger individuals. Its Methods use a 0.1–0.5 mIU/L category, not the cited 0.1–0.4 range; all-cause mortality is attached to a different citation in the citing sentence. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSerum thyrotropin levels below or above the reference range while taking levothyroxine have been associated with increased risk of adverse cardiovascular events.
“Serum thyrotropin levels below or above the reference range while taking levothyroxine have been associated with increased risk of adverse cardiovascular events. 72-75”
From Hypothyroidism: A Review (2025) · cites this paper as [73]
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References 34 · Cited by 43
Research works printed but not linked: 4
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- Authors
- Papaleontiou, M., Levine, D. A., Reyes-Gastelum, D., Hawley, S. T., Banerjee, M., & Haymart, M. R.
- Affiliations
- University of Michigan (US)
- Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
- Corresponding author
- Papaleontiou, Maria
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2021-06-17
- Volume
- 106
- Issue
- 10
- Pages
- e3890-e3900
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC8475197
- OpenAlex
- W3169976372
- Cited by
- 43
- References
- 34
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 10 · 2023: 5 · 2022: 9 · 2021: 2
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (K08 AG049684)
- Agency for Healthcare Research and Quality (R01 HS024512, R01 CA201198)
- National Cancer Institute
- 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 › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- thyroid hormone replacement, stroke, atrial fibrillation, thyroid-stimulating hormone, free thyroxine, thyroid function, drug safety, veterans
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Atrial Fibrillation, Female, Humans, Hypothyroidism, Male, Middle Aged, Retrospective Studies, Risk Factors, Thyroid Hormones, United States, Veterans, Cohort Studies, Incidence, Hormone Replacement Therapy, Stroke, Young Adult
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