Thyroid Function Within the Reference Range and the Risk of Stroke: An Individual Participant Data Analysis
Open accessAbstract
The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously. We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T4, and stroke outcomes were included, and we collected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L. We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1–13.9), including 449 908 person-years. Age- and sex-adjusted pooled hazard ratio for TSH was 0.78 (95% confidence interval [CI] 0.65–0.95 across the reference range of TSH) for all stroke and 0.83 (95% CI 0.62–1.09) for fatal stroke. For the free T4 analyses, the hazard ratio was 1.08 (95% CI 0.99–1.15 per SD increase) for all stroke and 1.10 (95% CI 1.04–1.19) for fatal stroke. This was independent of cardiovascular risk factors including systolic blood pressure, total cholesterol, smoking, and prevalent diabetes. Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within the reference range of thyroid function.
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A large, individual patient data meta-analysis showed that high TSH levels within the normal population range was associated with a lower risk of stroke.
“a large, individual patient data meta-analysis showed that high TSH levels within the normal population range was associated with a lower risk of stroke, 136”
From Hypothyroidism (2024) · cites this paper as [136]
A large individual-patient data meta-analysis identified that high TSH levels within the normal population range was associated with a lower risk of stroke.
“A large individual-patient data meta-analysis also identified that high TSH levels within the normal population range was associated with a lower risk of stroke [107].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [107]
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Self-citationThyroid Function Affects the Risk of Stroke via Atrial Fibrillation: A Mendelian Randomization Study
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Self-citationThyroid Function and Dysfunction in Relation to 16 Cardiovascular Diseases
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Self-citationDiabetes Mellitus and Osteoporosis Correlation: Challenges and Hopes
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Self-citationGenetics of Thyroid Function: Relevance for Biology and Disease Management
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NEUROPROTECTIVE EFFECT OF THYROID HORMONES IN CEREBRAL HYPOPERFUSION
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Thyroid and Cardiovascular Risk
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Response to the Letter by Choy
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Self-citationDaten zu Gunsten einer Levothyroxin-Substitution bei asymptomatischer latenter Hypothyreose
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Self-citationGenome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation
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Individualized prevention in cardiovascular disease and diabetes mellitus
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A Study on Ischemic Stroke Data Collected from Some Biochemical Analysis of Stroke Patients
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- Authors
- Chaker, L., Baumgartner, C., den Elzen, W. P. J., Collet, T.-H., Ikram, M. A., Blum, M. R., Dehghan, A., Drechsler, C., Luben, R. N., Portegies, M. L. P., Iervasi, G., Medici, M., Stott, D. J., Dullaart, R. P., Ford, I., Bremner, A., Newman, A. B., Wanner, C., Sgarbi, J. A., Dörr, M., Longstreth, W. T., Psaty, B. M., Ferrucci, L., Maciel, R. M. B., Westendorp, R. G., Jukema, J. W., Ceresini, G., Imaizumi, M., Hofman, A., Bakker, S. J. L., Franklyn, J. A., Khaw, K.-T., Bauer, D. C., Walsh, J. P., Razvi, S., Gussekloo, J., Völzke, H., Franco, O. H., Cappola, A. R., Rodondi, N., Peeters, R. P., & for the Thyroid Studies Collaboration
- Affiliations
- University of Bern (CH)
- Corresponding author
- Peeters, Robin P.
- ORCID
- Chaker, Layal
- Baumgartner, Christine
- Collet, Tinh-Hai
- Ikram, M. Arfan
- Blum, Manuel R.
- Dehghan, Abbas
- Drechsler, Christiane
- Luben, Robert N.
- Iervasi, Giorgio
- Medici, Marco
- Stott, David J.
- Dullaart, Robin P.
- Ford, Ian
- Bremner, Alexandra
- Newman, Anne B.
- Wanner, Christoph
- Sgarbi, José A.
- Dörr, Marcus
- Psaty, Bruce M.
- Ferrucci, Luigi
- Maciel, Rui M. B.
- Westendorp, Rudi G.
- Jukema, J. Wouter
- Ceresini, Graziano
- Bakker, Stephan J. L.
- Khaw, Kay-Tee
- Bauer, Douglas C.
- Walsh, John P.
- Razvi, Salman
- Gussekloo, Jacobijn
- Völzke, Henry
- Franco, Oscar H.
- Cappola, Anne R.
- Rodondi, Nicolas
- Peeters, Robin P.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-11
- Volume
- 101
- Issue
- 11
- Pages
- 4270-4282
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC5095234
- OpenAlex
- W2516199888
- Cited by
- 92
- References
- 63
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 10 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 13 · 2019: 11 · 2018: 9 · 2017: 15
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- UWA Profiles and Research Repository (University of Western Australia) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- U.S. Department of Energy
- Yale University
- University of Washington
- University of Pittsburgh
- National Institute for Health and Care Research (NF-SI-0512-10114)
- Deutsche Forschungsgemeinschaft
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (320 030-150 025, 150025, 138267, 145870, 320030, 155318)
- Universiteit Leiden
- Rijksuniversiteit Groningen
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- ZonMw (91212044)
- Nierstichting (E.033, 2001-005)
- Erasmus Medisch Centrum
- Ministry of Health, Labour and Welfare
- Università degli Studi di Parma
- Faculdade de Medicina de Marília
- Leids Universitair Medisch Centrum
- Universitair Medisch Centrum Groningen
- Universidade de São Paulo
- Faculty of Health and Medical Sciences, University of Western Australia
- National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc085079-024, UL1TR000128, n01hc085083-027, n01hc085080-026, n01hc085086-022, HHSN268200800007C, HHSN268201200036C, n01hc055222-001, AG042139, N01HC85086, AR066160, N01-HC-85082, AG042140, N01HC85079, AG027810, N01HC85080, TR000128, N01HC85083, N01-HC-85081, AG042124, AG042143, HL080295, AG042145)
- University of California, San Francisco (N01HC55222, HHSN268200800007C, N01HC85082, HHSN268201200036C, N01HC85081, N01HC85083, N01HC85079, N01HC85080, N01HC85086)
- Medical Research Council (MR/N003284/1)
- Det Sundhedsvidenskabelige Fakultet, Københavns Universitet
- Erasmus Universitair Medisch Centrum Rotterdam
- National Institute on Aging (R01‐NR012459, N01HC85081, N01HC85079, U01AG042145, N01-HC-85080, N01-HC-85082, U01AG042168, R01AG028050, R56AG023629, R01AG032317, AG042140, N01HC55222, HHSN268200800007C, AG042139, U01AG042143, AG042168, U01AG027810, AG042124, N01-HC-85083, AG042145, AG023629, U01AG042139, HL080295, U01AG042124, K24AG042765, AG027810, U01AG042140, N01‐HC‐85086, R01AG023629, AG042143, HHSN268201200036C, P30AG024827)
- National Heart, Lung, and Blood Institute (N01-HC-85081, N01 HC085086, AG-023629, N01HC-85083, R01-NR012459, N01 HC085079, N01 HC085083, N01HC85082, N01 HC85086, N01 HC085080, HHSN 268200800007C, N01HC85080, N01 HC55222, HHSN268201200036C, N01HC085082, U01HL080295, N01 HC055222, N01 HC085081, HL080295, R01HL080295, N01-HC85079)
- National Institute of Nursing Research (R01NR012459)
- National Institute of Neurological Disorders and Stroke (AG023629, R01-NR012459, HHSN268200800007C, N01-HC-85080, HL080295, N01-HC-85083, N01HC85082, N01-HC-85081, R01-AG028050, N01-HC-85086, N01 HC-55222, N01HC85079, HHSN268201200036C)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (U01AR066160, AR066160, K24AR051895)
- National Center for Advancing Translational Sciences (TR000128)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- thyroid function, thyroid-stimulating hormone, free thyroxine, stroke risk, fatal stroke, reference values, thyroid function tests, cardiovascular risk factors
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Dextrothyroxine, Female, Follow-Up Studies, Humans, Male, Middle Aged, Reference Values, Risk, Thyrotropin, Stroke, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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