Increased cardiovascular risk in thyroid cancer patients taking levothyroxine: a nationwide cohort study in Korea

in European Journal of Endocrinology
Correspondence should be addressed to Y Park; Email:

*(B Suh and D W Shin contributed equally to this work)

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Many thyroid cancer patients are exposed to long-term thyroid-stimulating hormone (TSH) suppression, often as lifetime treatment, and are consequently at risk for cardiovascular disease. We investigated the incidence of coronary heart disease (CHD) and ischemic stroke among thyroid cancer patients compared with matched control subjects.


Retrospective cohort study.


A total of 182 419 subjects who received thyroidectomy for thyroid cancer during 2004–2012 were selected from the Korean National Health Insurance data, which cover approximately 97% of the entire Korean population. Propensity score matching was used to select non-cancer controls. Cox proportional hazards regression analysis was used to determine relative risk of coronary heart disease and ischemic stroke. Mean follow-up was 4.32 years.


Thyroid cancer patients had elevated risk for CHD and ischemic stroke with hazard ratio (HR) of 1.15 (95% confidence interval (CI): 1.10–1.22) and 1.15 (1.09–1.22), respectively. This risk was increased in those who took a higher dosage of levothyroxine (HR: 1.47, 95% CI: 1.34–1.60 for CHD and HR: 1.56, 95% CI: 1.42–1.72 for ischemic stroke among those who took ≥170 μg/day levothyroxine). Although risk of atrial fibrillation was dose-dependently associated with levothyroxine dosage, it represents only a small proportion of ischemic stroke incidence (4.4%, 128/2914).


The risk for CHD and ischemic stroke was higher in thyroid cancer patients who received thyroidectomy, and the dosage of levothyroxine administered appears to play a major role. Greater caution is suggested for the screening and treatment of thyroid cancer and subsequent TSH suppression therapy, as well as proper management for cardiovascular disease prevention.


     European Society of Endocrinology

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    Selection scheme for study population.

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    Kaplan–Meier curves for incidence of coronary heart disease and ischemic stroke among thyroid cancer patients. Kaplan–Meier curves for coronary heart disease incidence (Panel A) and ischemic stroke incidence (Panel B), where post-thyroidectomy thyroid cancer patients (case) are compared to matched controls. P values indicate results from log-rank tests.

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    Forest plots for coronary heart disease and ischemic stroke incidence among thyroid cancer patients and matched controls. Hazard ratios were determined by univariable Cox proportional hazards regression analysis of specific case subjects compared to individually matched controls. Rates are indicated per 1000 person-years. LT4, levothyroxine; TT, total thyroidectomy; UL, unilateral lobectomy.

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    Involvement of atrial fibrillation in risk of ischemic stroke incidence among thyroid cancer patients. Hazard ratios were determined by multivariable Cox proportional hazards regression analysis adjusted by age, sex, hypertension, diabetes, and dyslipidemia. Rate is indicated per 1000 person-years. Afib, atrial fibrillation; LT4, levothyroxine.



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