Background: Studies on adults have shown an association between overt or subclinical hypothyroidism and metabolic dysfunction-associated steatotic liver disease (MASLD). The goal of this study was to assess the relationship between thyroid-stimulating hormone (TSH) levels and the histological characteristics of MASLD in youth.
Methods: This observational study used prospectively collected liver biopsy and clinical data from youth enrolled in 2 pediatric clinical trials in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Thyroid assays were compared between youth with MASLD and population-based controls aged ≤18 years from the National Health and Nutrition Examination Survey. Individuals with overt hypothyroidism, abnormal antithyroid antibodies, or thyroid-related medications were excluded. Subclinical hypothyroidism was defined as TSH between 4.5 and 10.0 uIU/L. Multinomial logistic regression was used to test the association between TSH and MASLD histological changes at baseline, adjusting for age, sex, race/ethnicity, and body mass index. Mixed-effect models, including treatment and time, were used for the longitudinal analysis.
Results: Mean TSH, total thyroxine (T4), total triiodothyronine (T3), and free T4 levels were higher ( p < 0.001) in the NASH CRN cohort (n = 218; 421 observations) than in the National Health and Nutrition Examination Survey cohort (n = 2198). TSH levels were positively associated with increased steatosis over time ( p = 0.03). Subclinical hypothyroidism was associated with borderline or definite metabolic-associated steatohepatitis on histology at baseline ( p = 0.03) and with changes in fibrosis over time ( p = 0.01).
Conclusions: The association between TSH and steatosis severity in individuals with normal thyroid hormone concentrations suggests an independent role of TSH in MASLD.
Keywords: MASLD; TSH; liver disease; pediatrics; thyroid function.
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