Untalan Matthew, A Crimmins Nancy, Yates Katherine P, A Mencin Ali, A Xanthakos Stavra, Thaker Vidhu V
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
Division of Gastroenterology, Department of Pediatrics, Hepatology and Nutrition, Cincinnati Children's Hospital and Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Hepatology. 2024 Sep 18. doi: 10.1097/HEP.0000000000001095.
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.
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.
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).
The association between TSH and steatosis severity in individuals with normal thyroid hormone concentrations suggests an independent role of TSH in MASLD.
针对成年人的研究表明，显性或亚临床甲状腺功能减退与代谢功能障碍相关脂肪性肝病（MASLD）之间存在关联。本研究的目的是评估青年人群中促甲状腺激素（TSH）水平与MASLD组织学特征之间的关系。
这项观察性研究前瞻性收集了参与非酒精性脂肪性肝炎临床研究网络（NASH CRN）两项儿科临床试验的青年人群的肝活检和临床数据。将患有MASLD的青年与来自美国国家健康与营养检查调查中年龄≤18岁的基于人群的对照组进行甲状腺检测比较。排除患有显性甲状腺功能减退、抗甲状腺抗体异常或服用甲状腺相关药物的个体。亚临床甲状腺功能减退定义为TSH在4.5至10.0 uIU/L之间。采用多项逻辑回归分析在基线时测试TSH与MASLD组织学变化之间的关联，并对年龄、性别、种族/族裔和体重指数进行校正。采用包括治疗和时间因素的混合效应模型进行纵向分析。
NASH CRN队列（n = 218；421次观察）中的平均TSH、总甲状腺素（T4）、总三碘甲状腺原氨酸（T3）和游离T4水平高于美国国家健康与营养检查调查队列（n = 2198）（p < 0.001）。随着时间的推移，TSH水平与脂肪变性增加呈正相关（p = 0.03）。亚临床甲状腺功能减退与基线时组织学上的临界或明确的代谢相关脂肪性肝炎相关（p = 0.03），并与随时间的纤维化变化相关（p = 0.01）。
甲状腺激素浓度正常的个体中TSH与脂肪变性严重程度之间的关联表明TSH在MASLD中具有独立作用。
