Prevalence of subclinical hypothyroidism and longitudinal thyroid stimulating hormone changes in youth with metabolic dysfunction-associated steatotic liver disease: an observational study

Background: Studies on adults have shown an association between overt or subclinical hypothyroidism (SH) 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 two 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 (NHANES). Individuals with overt hypothyroidism, abnormal anti-thyroid antibody, or thyroid-related medications were excluded. SH was defined as TSH between 4.5–10.0 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 NHANES cohort (n=2,198). TSH levels were positively associated with increased steatosis over time (p=0.03). SH 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). Conclusion: The association between TSH and steatosis severity in individuals with normal thyroid hormone concentrations suggests an independent role of TSH in MASLD.