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J Clin Endocrinol Metab. 2015 Jun;100(6):2181-91. doi: 10.1210/jc.2015-1438. Epub 2015 Apr 9.

Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis.

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Department of Internal Medicine (L.C., M.M., R.P.P.), and Rotterdam Thyroid Center, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Epidemiology (L.C., M.A.I., A.D., A.H., M.L.P.P., O.H.F.), Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of General Internal Medicine (C.B., M.R.B., N.R.), Inselspital, Bern University Hospital, 3010 Bern, Switzerland; Departments of Epidemiology, Public Health, and Primary Care (W.P.J.d.E., J.G.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Department of Radiology (M.A.I.), Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands; Department of Neurology (M.A.I., M.L.P.P.), Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands; Service of Endocrinology, Diabetes, and Metabolism (T.-H.C.), University Hospital of Lausanne, 1011 Lausanne, Switzerland; Department of Internal Medicine (S.J.L.B., R.P.D.), University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Department of Medicine (C.D., C.W.), Division of Nephrology, University Hospital of Würzburg, Germany Comprehensive Heart Failure Centre, D-97080 Würzburg, Germany; Department of Public Health and Primary Care (R.N.L., K.-T.K.), University of Cambridge, Cambridge CB2 1TN, United Kingdom; National Council Research Institute of Clinical Physiology (G.I.), Pisa 56124, Italy; Institute of Cardiovascular and Medical Sciences, Faculty of Medicine (D.J.S.), and Robertson Centre for Biostatistics (I.F.), University of Glasgow, Glasgow G12 8QQ, United Kingdom; School of Population Health (A.B.), University of Western Australia, Crawley, Perth 6009, Western Australia, Australia; National Institute on Aging (L.F.), Baltimore, Maryland 20892; Department of Epidemiology (A.B.N.), University of Pittsburgh, Pittsburgh, Pennsylvania 15260; Division of Endocrinology (J.A.S.), Faculdade de Medicina de Marília, Marília, Sao Paulo 17519, Brazil; Di



The objective was to determine the risk of stroke associated with subclinical hypothyroidism.


Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels.


We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95% CI, 1.08-16.55) and 2.86 (95% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95% CI, 0.86-1.18) or ≥ 80 years old (HR, 1.31; 95% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations.


Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.

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