Exploring the link between metabolic dysfunction-associated fatty liver disease and subclinical hypothyroidism in adolescents: a comprehensive review

Background/objectives: Metabolic dysfunction-associated fatty liver disease (MAFLD) and subclinical hypothyroidism (SCH) increasingly co-occur in adolescents, yet their inter-relationship and clinical relevance remain uncertain. Objective: To synthesize evidence on epidemiologic associations, shared mechanisms, and care implications linking MAFLD and SCH in youth. Methods: We conducted a structured review of PubMed, Embase, Web of Science, and the Cochrane Library from inception to December 31, 2024, focusing on pediatric observational studies and mechanistic or interventional data relevant to adolescents. Two reviewers screened studies and extracted design, diagnostics, exposures (TSH/thyroid hormones), outcomes (steatosis severity, fibrosis, liver enzymes), and adjusted effect estimates. Risk of bias was narratively assessed for observational designs. Results: Pediatric cohorts consistently report a positive association between higher TSH (within the reference or mildly elevated range) and hepatic steatosis severity, with several studies indicating a dose-response gradient. Mechanistic evidence suggests TSHR-SREBP-1c signaling, insulin resistance, adipokine imbalance, low-grade inflammation, and gut-liver-thyroid crosstalk as plausible pathways. Adult interventional data show that levothyroxine therapy for SCH can modestly reduce liver fat and aminotransferases; however, pediatric trials are lacking. Definitions, diagnostic modalities, and confounding control vary across studies, and most pediatric evidence is cross-sectional, limiting causal inference. Conclusions: In adolescents, MAFLD and SCH appear linked through metabolic and endocrine pathways, but causality remains unproven. Risk-based screening may be warranted-thyroid testing in MAFLD and targeted liver assessment in persistent SCH-while longitudinal cohorts and pediatric trials are needed to define thresholds for intervention and potential benefits of endocrine management.