Donghee Kim1, Luis Miguel Vazquez-Montesino2, Jessica A Escober1, Christopher T Fernandes1, George Cholankeril1, Rohit Loomba3,4, Stephen A Harrison5,6, Zobair M Younossi7, Aijaz Ahmed1. 1. Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA. 2. Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. 3. NAFLD Research Center, University of California at San Diego, La Jolla, California, USA. 4. Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, California, USA. 5. Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. 6. Pinnacle Clinical Research, San Antonio, Texas, USA. 7. Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Virginia, USA.
Abstract
INTRODUCTION: Higher levels of thyroid-stimulating hormone (TSH) in the euthyroid state can negatively affect the metabolic health, including nonalcoholic fatty liver disease (NAFLD). We studied the effect of TSH levels in the setting of normal levels of thyroid hormone on all-cause and cause-specific mortality stratified by NAFLD status. METHODS: The National Health and Nutrition Examination Survey (NHANES) III from 1988 to 1994 and NHANES III-linked mortality data through 2015 were used. NAFLD was defined as ultrasonographically diagnosed hepatic steatosis without coexisting liver diseases. Subclinical hypothyroidism was defined as a TSH level over 4.5 mIU/L and "low-normal" thyroid function as higher TSH level (2.5-4.5 mIU/L) within the euthyroid reference range. The Cox proportional hazard model analyzed the all-cause mortality and cause-specific mortality. RESULTS: In a multivariate logistic regression analysis, individuals with low thyroid function demonstrated an association with NAFLD in a dose-dependent manner. During a median follow-up of 23 years, low thyroid function was associated with increased all-cause mortality only in the univariate model. Low thyroid function was associated with a higher risk for all-cause mortality in individuals with NAFLD and not in those without NAFLD. Furthermore, low thyroid function was associated with a higher risk for cardiovascular mortality in the entire population and among those with NAFLD but demonstrated no association with the non-NAFLD group. DISCUSSION: In this large nationally representative sample of American adults, low thyroid function was associated with NAFLD and a predictor of higher risk for all-cause and cardiovascular mortality in individuals with NAFLD.
INTRODUCTION: Higher levels of thyroid-stimulating hormone (TSH) in the euthyroid state can negatively affect the metabolic health, including nonalcoholic fatty liver disease (NAFLD). We studied the effect of TSH levels in the setting of normal levels of thyroid hormone on all-cause and cause-specific mortality stratified by NAFLD status. METHODS: The National Health and Nutrition Examination Survey (NHANES) III from 1988 to 1994 and NHANES III-linked mortality data through 2015 were used. NAFLD was defined as ultrasonographically diagnosed hepatic steatosis without coexisting liver diseases. Subclinical hypothyroidism was defined as a TSH level over 4.5 mIU/L and "low-normal" thyroid function as higher TSH level (2.5-4.5 mIU/L) within the euthyroid reference range. The Cox proportional hazard model analyzed the all-cause mortality and cause-specific mortality. RESULTS: In a multivariate logistic regression analysis, individuals with low thyroid function demonstrated an association with NAFLD in a dose-dependent manner. During a median follow-up of 23 years, low thyroid function was associated with increased all-cause mortality only in the univariate model. Low thyroid function was associated with a higher risk for all-cause mortality in individuals with NAFLD and not in those without NAFLD. Furthermore, low thyroid function was associated with a higher risk for cardiovascular mortality in the entire population and among those with NAFLD but demonstrated no association with the non-NAFLD group. DISCUSSION: In this large nationally representative sample of American adults, low thyroid function was associated with NAFLD and a predictor of higher risk for all-cause and cardiovascular mortality in individuals with NAFLD.
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