REVIEW article
Front. Pediatr.
Sec. Children and Health
Exploring the Link Between Metabolic Dysfunction-Associated Fatty Liver Disease and Subclinical Hypothyroidism in Adolescents: A Comprehensive Review
Provisionally accepted
- 1Aerospace Center Hospital, Beijing, China
- 2Peking University International Hospital, Beijing, China
- 3Beijing University of Chinese Medicine Affiliated Dongzhimen Hospital, Beijing, China
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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.
Keywords: Metabolic dysfunction-associated fatty liver disease (MAFLD), Subclinical hypothyroidism (SCH), Thyroid-stimulating hormone (TSH), Insulin Resistance, adolescents
Received: 19 Sep 2025; Accepted: 15 Jan 2026.
Copyright: © 2026 Hu, Shi, Xu, Li, Yao, Yu and Qu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jun Qu
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