Subclinical Hypothyroidism in NAFLD Is Associated With All-Cause and Cardiovascular Mortality

Low thyroid function is associated with nonalcoholic fatty liver disease (NAFLD) and predicted all-cause and cardiovascular mortality in this population, according to the results of a study published in The American Journal of Gastroenterology.

To determine the association of low thyroid function with all-cause and cause-specific mortality in individuals with NAFLD, data from 10,144 individuals aged 20 to 74 years (48.4% men) from the 1988 to 1994 National Health and Nutrition Examination Survey (NHANES) were analyzed. Individuals who were prescribed thyroid medications, had a history of thyroid disease, or had overt hypothyroidism or hyperthyroidism were excluded.

Subclinical hypothyroidism was defined as a thyrotropin (TSH) level >4.5 mU/L, low-normal thyroid function was defined as a TSH level of 2.5 to 4.5 mU/L, and strict-normal thyroid function was defined as a TSH level of 0.39 to 2.5 mU/L. Subclinical hypothyroidism and low-normal thyroid function together were considered low thyroid function. NAFLD diagnosis was established by the presence of any degree of steatosis of without any other known causes for liver disease.

The mean age of included individuals was 42.4 years. Of the included individuals, 33.9% had NAFLD, of whom 81.8% had strict-normal thyroid function, 13.9% had low-normal thyroid function, and 4.3% had subclinical hypothyroidism. Compared with individuals with strict-normal thyroid function, individuals with low thyroid function were more likely to be older, female, and non-Hispanic white.

The prevalence of NAFLD correlated significantly with increasing TSH levels (P <.001). In multivariate analysis, low thyroid function was associated with risk for NAFLD (odds ratio [OR], 1.29; 95% CI, 1.06-1.57; P <.014) compared with strict-normal thyroid function. Specifically, low-normal thyroid function was associated with a 25% increased risk for NAFLD (OR, 1.25; 95% CI, 0.99-1.56) and subclinical hypothyroidism was associated with a 42% increased risk for NAFLD (OR, 1.42; 95% 1.07-1.88) compared with strict-normal thyroid functioning (P =.005 for trend).

There were a total of 2978 deaths in the median 23 years of follow-up. When considering known demographic variables and traditional risk factors, low thyroid function and NAFLD status were not independently significantly associated with all-cause mortality, but co-occurrence of low thyroid function and NAFLD was significantly associated with an increased risk for all-cause mortality (hazard ratio [HR], 1.24; 95%, 1.02-1.50; P =.031) compared with individuals with NAFLD and strict-normal thyroid function.

Low thyroid function was also significantly associated with an increased risk for cardiovascular mortality in the total population (HR, 1.28; 95% CI 1.03-1.58; P =.025) and for individuals with NAFLD (HR, 1.62; 95% CI, 1.11-2.34; P =.013) compared with individuals with strict-normal thyroid function. Among individuals with NAFLD, low-normal thyroid function was associated with a 50% increased risk for cardiovascular mortality (HR, 1.50; 95% CI, 0.97-2.33) and subclinical thyroid function was associated with a 94% increased risk for cardiovascular mortality (HR, 1.94; 95% CI, 1.10-3.42; P =.006 for trend) compared with individuals with strict-normal thyroid function.

Taken together, these findings suggested “a strong association of NAFLD with increasing plasma TSH levels and all-cause mortality, largely related to cardiovascular complications,” as noted by the study authors. Individuals with NAFLD who had elevated TSH levels still within the euthyroid range had an increased risk for all-cause and cardiovascular mortality.

Limitations to this study included its cross-sectional nature; lack of data on serial thyroid function testing, ultrasonography, and thyroxine levels; and the use of ultrasonography in the diagnosis of NAFLD, which has limited sensitivity.

Reference

Kim D, Vazquez-Montesino LM, Escober JA, et al. Low thyroid function in nonalcoholic fatty liver disease is an independent predictor of all-cause and cardiovascular mortality [published online June 3, 2020]. Am J Gastroenterol. doi:10.14309/ajg.0000000000000654