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

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.

Evaluating health outcomes in the treatment of hypothyroidism

“…Of note, TSH levels over the time course of the study were not included in either study, and those treated for subclinical hypothyroidism were likely included in the claims-based study ( 27 ). Conversely, a recent study of a large retrospective Korean claims database found all-cause mortality rates were increased in levothyroxine-treated patients (N=501,882; thyroid function tests were not reported) compared to a control cohort (N=1,505,646), with relative risk being higher in patients under 65 years of age and in those with higher cardiovascular risk at baseline ( 29 ). Similar to the previous studies, a major limitation of this study is that no thyroid function tests were collected in the study, and patients treated for overt and subclinical hypothyroidism could not be differentiated.…”

Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database

“…Regarding the long-term prognosis of hyperthyroidism, increased risks for AF [66], HF [67], MI [68], and IS [68], accompanied by a consequent increase in mortality, have been reported, raising awareness of these issues among clinicians and patients. Interestingly, a study also reported that all-cause mortality was higher in patients with hypothyroidism receiving levothyroxine-treatment than in controls who were not diagnosed with hypothyroidism [69]. Two interesting reports regarding COV-ID-19 have recently been published.…”

Event dependent overall survival in the population-based LIFE-Adult-Study

“…But in most cases, mortality associated with a particular risk factor or disease is determined, e.g. hypertension [ 3 ], diabetes mellitus [ 4 ] or hypothyroidism [ 5 ]. Independent examination of medical history, as it is done here, provides an open-ended approach to examine the general risks of particular diagnoses in medical history in a mixed population.…”