Risk of All-Cause Mortality in Levothyroxine-Treated Hypothyroid Patients: A Nationwide Korean Cohort Study.

Seo Young Sohn,Gi Hyeon Seo,Jae Hoon Chung

doi:10.3389/fendo.2021.680647

Abstract

BackgroundAlthough hypothyroidism is associated with various comorbidities, its relationship with increased all-cause mortality remains controversial. The aim of this nationwide retrospective cohort study was to investigate whether hypothyroid patients treated with levothyroxine had increased mortality compared to controls.MethodsHypothyroid subjects were identified through the Korean National Health Insurance Service Claims database between 2008 and 2017. Hypothyroidism in this study was defined as overt hypothyroidism treated with long-term prescription of levothyroxine (>6 months). After 1:3 age-, sex- and index year-matching, 501,882 patients with newly diagnosed hypothyroidism and 1,505,646 controls without hypothyroidism were included.ResultsDuring a mean follow-up of 6 years, 25,954 (5.2%) hypothyroid patients and 59,105 (3.9%) controls died. Hypothyroidism was significantly associated with increased all-cause mortality (adjusted hazard ratio [HR], 1.14; 95% confidence interval [CI] 1.12–1.16) even with levothyroxine treatment. When stratified by age, sex, and cardiovascular disease risk, independent associations between hypothyroidism and mortality remained significant in all subgroups. The risk of mortality was higher in the < 65 age group (HR: 1.25, 95% CI: 1.22–1.29), men (HR: 1.28, 95% CI: 1.25–1.31), and the high cardiovascular disease risk group (HR: 1.31, 95% CI: 1.29–1.34). The mortality rate of hypothyroid patients was highest within 1 year of treatment and decreased with time.ConclusionThis nationwide, population-based cohort study showed that all-cause mortality was significantly higher in levothyroxine-treated hypothyroid patients than in non-hypothyroid controls. This association remained significant regardless of age, sex, and cardiovascular disease risk.

Highlights

Hypothyroidism is a common endocrine disease, and its incidence and prevalence vary depending on the population being studied [1,2,3]
Regardless of cause, hypothyroidism is associated with a number of well-characterized metabolic changes, such as hyperlipidemia, hypertension, and coagulopathy, as well as endothelial dysfunction and cardiovascular disorders [6,7,8,9,10], all of which could theoretically lead to increased mortality
Most have been restricted to subjects with subclinical hypothyroidism [17, 20, 21, 28, 29, 33, 34, 38] and some studies have defined hypothyroidism based on only one thyroid-stimulating hormone (TSH) level measurement [13, 15, 22, 28, 30, 37]. These studies may not represent patients with hypothyroidism who require long-term thyroid hormone replacement. In this nationwide retrospective cohort study, we investigated all-cause mortality risks of hypothyroid patients undergoing long-term levothyroxine therapy compared to age- and sexmatched control subjects

Summary

Introduction

Hypothyroidism is a common endocrine disease, and its incidence and prevalence vary depending on the population being studied [1,2,3]. Some studies have found an increased risk of mortality in hypothyroid patients [12,13,14, 16, 17, 19, 21,22,23,24], but others have not [11, 15, 18, 20]. Hypothyroidism is associated with various comorbidities, its relationship with increased all-cause mortality remains controversial. The aim of this nationwide retrospective cohort study was to investigate whether hypothyroid patients treated with levothyroxine had increased mortality compared to controls

Methods

Results

Conclusion