Thyroid Hormone Therapy and Incident Stroke

J Clin Endocrinol Metab. 2021 Sep 27;106(10):e3890-e3900. doi: 10.1210/clinem/dgab444.


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.

Keywords: atrial fibrillation; stroke; thyroid hormone therapy.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / epidemiology
  • Cohort Studies
  • Female
  • Hormone Replacement Therapy / statistics & numerical data
  • Humans
  • Hypothyroidism / drug therapy*
  • Hypothyroidism / epidemiology
  • Incidence
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Stroke / epidemiology*
  • Thyroid Hormones / therapeutic use*
  • United States / epidemiology
  • Veterans / statistics & numerical data
  • Young Adult


  • Thyroid Hormones