Liyuan Zhou, Lanxuan Jiang, Yu An, Jia Liu, Guang Wang, Ying Wang, Ning Yang
{"title":"甲状腺功能正常成人甲状腺激素敏感性与非酒精性脂肪性肝病及肝纤维化严重程度的相关性：一项回顾性研究","authors":"Liyuan Zhou, Lanxuan Jiang, Yu An, Jia Liu, Guang Wang, Ying Wang, Ning Yang","doi":"10.2147/DMSO.S499517","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The relationship between non-alcoholic fatty liver disease (NAFLD) and thyroid function is controversial. A mild acquired thyroid hormone resistance may exist and explain these contradictions. This study aims to investigate the associations of thyroid hormone sensitivity with NAFLD and the severity of liver fibrosis in euthyroid populations.</p><p><strong>Patients and methods: </strong>Twenty-nine thousand three hundred and eighty-six adult subjects were recruited from the medical examination center of the Beijing Chao-Yang Hospital. Free triiodothyronine (FT3)/free thyroxine (FT4), thyroid feedback quartile-based index for FT4 (TFQI<sub>FT4</sub>) and for FT3 (TFQI<sub>FT3</sub>), thyroid stimulating hormone index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and thyrotropin triiodothyronine resistance index (TT3RI) were calculated. Logistic regression analysis was used to analyze the associations of thyroid hormone sensitivity indices with the risks of NAFLD and related metabolic disorders. The correlation between thyroid hormone sensitivity and the severity of liver fibrosis evaluated by noninvasive fibrosis indices was analyzed through ordinal logistic regression.</p><p><strong>Results: </strong>Euthyroid adults with NAFLD had elevated levels of serum FT3 and FT4, reduced TSH, and impaired sensitivity to thyroid hormones. Compared with participants in the first quartile group, the risk of NAFLD was higher in the fourth quartile of TFQI<sub>FT3</sub> (OR 1.25, 95% CI 1.13-1.39, P < 0.001) and FT3/FT4 (OR 1.45, 95% CI 1.32-1.60, P < 0.001) after adjusting for metabolic confounders. Among NAFLD patients, higher FT3/FT4 positively correlated with increased severity of liver fibrosis, with ORs per SD of 10.80 (95% CI 4.12-28.53, P < 0.001) for aminotransferase-to-platelet ratio index, 4.74 (95% CI 1.56-14.38, P = 0.006) for NAFLD fibrosis score and 3.21 (95% CI 1.02-10.08, P = 0.046) for fibrosis-4 index.</p><p><strong>Conclusion: </strong>Impaired central sensitivity to FT3 and higher FT3/FT4 were associated with increased risks of NAFLD and related metabolic disorders. In patients with NAFLD, higher FT3/FT4 correlated with its progression to liver fibrosis. These findings might provide novel insight into the monitoring and evaluation of the risk of NAFLD and the severity of liver fibrosis.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"479-490"},"PeriodicalIF":2.8000,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844316/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association of Sensitivity to Thyroid Hormones and Non-Alcoholic Fatty Liver Disease and the Severity of Liver Fibrosis in Euthyroid Adults: A Retrospective Study.\",\"authors\":\"Liyuan Zhou, Lanxuan Jiang, Yu An, Jia Liu, Guang Wang, Ying Wang, Ning Yang\",\"doi\":\"10.2147/DMSO.S499517\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The relationship between non-alcoholic fatty liver disease (NAFLD) and thyroid function is controversial. A mild acquired thyroid hormone resistance may exist and explain these contradictions. This study aims to investigate the associations of thyroid hormone sensitivity with NAFLD and the severity of liver fibrosis in euthyroid populations.</p><p><strong>Patients and methods: </strong>Twenty-nine thousand three hundred and eighty-six adult subjects were recruited from the medical examination center of the Beijing Chao-Yang Hospital. Free triiodothyronine (FT3)/free thyroxine (FT4), thyroid feedback quartile-based index for FT4 (TFQI<sub>FT4</sub>) and for FT3 (TFQI<sub>FT3</sub>), thyroid stimulating hormone index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and thyrotropin triiodothyronine resistance index (TT3RI) were calculated. Logistic regression analysis was used to analyze the associations of thyroid hormone sensitivity indices with the risks of NAFLD and related metabolic disorders. The correlation between thyroid hormone sensitivity and the severity of liver fibrosis evaluated by noninvasive fibrosis indices was analyzed through ordinal logistic regression.</p><p><strong>Results: </strong>Euthyroid adults with NAFLD had elevated levels of serum FT3 and FT4, reduced TSH, and impaired sensitivity to thyroid hormones. Compared with participants in the first quartile group, the risk of NAFLD was higher in the fourth quartile of TFQI<sub>FT3</sub> (OR 1.25, 95% CI 1.13-1.39, P < 0.001) and FT3/FT4 (OR 1.45, 95% CI 1.32-1.60, P < 0.001) after adjusting for metabolic confounders. Among NAFLD patients, higher FT3/FT4 positively correlated with increased severity of liver fibrosis, with ORs per SD of 10.80 (95% CI 4.12-28.53, P < 0.001) for aminotransferase-to-platelet ratio index, 4.74 (95% CI 1.56-14.38, P = 0.006) for NAFLD fibrosis score and 3.21 (95% CI 1.02-10.08, P = 0.046) for fibrosis-4 index.</p><p><strong>Conclusion: </strong>Impaired central sensitivity to FT3 and higher FT3/FT4 were associated with increased risks of NAFLD and related metabolic disorders. In patients with NAFLD, higher FT3/FT4 correlated with its progression to liver fibrosis. These findings might provide novel insight into the monitoring and evaluation of the risk of NAFLD and the severity of liver fibrosis.</p>\",\"PeriodicalId\":11116,\"journal\":{\"name\":\"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy\",\"volume\":\"18 \",\"pages\":\"479-490\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-02-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844316/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/DMSO.S499517\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DMSO.S499517","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
摘要
目的：非酒精性脂肪肝（NAFLD）与甲状腺功能之间的关系存在争议。可能存在轻微的获得性甲状腺激素抵抗，从而解释了这些矛盾。本研究旨在调查甲状腺激素敏感性与非酒精性脂肪肝以及甲状腺功能正常人群肝纤维化严重程度的关系：从北京朝阳医院体检中心招募了2.9万386名成年受试者。计算游离三碘甲状腺原氨酸（FT3）/游离甲状腺素（FT4）、基于甲状腺反馈的FT4四分位指数（TFQIFT4）和FT3四分位指数（TFQIFT3）、促甲状腺激素指数（TSHI）、促甲状腺激素甲状腺素抵抗指数（TT4RI）和促甲状腺激素三碘甲状腺原氨酸抵抗指数（TT3RI）。采用逻辑回归分析法分析甲状腺激素敏感性指数与非酒精性脂肪肝及相关代谢紊乱风险的关系。通过序数逻辑回归分析了甲状腺激素敏感性与非侵入性肝纤维化指数评估的肝纤维化严重程度之间的相关性：结果：患有非酒精性脂肪肝的甲状腺功能正常成人的血清FT3和FT4水平升高，促甲状腺激素水平降低，对甲状腺激素的敏感性降低。与第一四分位组的参与者相比，在调整代谢混杂因素后，TFQIFT3（OR 1.25，95% CI 1.13-1.39，P＜0.001）和FT3/FT4（OR 1.45，95% CI 1.32-1.60，P＜0.001）处于第四四分位的非酒精性脂肪肝风险更高。在非酒精性脂肪肝患者中，较高的FT3/FT4与肝纤维化严重程度的增加呈正相关，转氨酶与血小板比值指数的OR值为每SD 10.80（95% CI 4.12-28.53，P＜0.001），非酒精性脂肪肝纤维化评分为4.74（95% CI 1.56-14.38，P＝0.006），纤维化-4指数为3.21（95% CI 1.02-10.08，P＝0.046）：结论：FT3中枢敏感性受损和FT3/FT4升高与非酒精性脂肪肝及相关代谢紊乱的风险增加有关。在非酒精性脂肪肝患者中，较高的FT3/FT4与肝纤维化的进展相关。这些发现可能会为监测和评估非酒精性脂肪肝的风险和肝纤维化的严重程度提供新的见解。
Association of Sensitivity to Thyroid Hormones and Non-Alcoholic Fatty Liver Disease and the Severity of Liver Fibrosis in Euthyroid Adults: A Retrospective Study.
Purpose: The relationship between non-alcoholic fatty liver disease (NAFLD) and thyroid function is controversial. A mild acquired thyroid hormone resistance may exist and explain these contradictions. This study aims to investigate the associations of thyroid hormone sensitivity with NAFLD and the severity of liver fibrosis in euthyroid populations.
Patients and methods: Twenty-nine thousand three hundred and eighty-six adult subjects were recruited from the medical examination center of the Beijing Chao-Yang Hospital. Free triiodothyronine (FT3)/free thyroxine (FT4), thyroid feedback quartile-based index for FT4 (TFQIFT4) and for FT3 (TFQIFT3), thyroid stimulating hormone index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and thyrotropin triiodothyronine resistance index (TT3RI) were calculated. Logistic regression analysis was used to analyze the associations of thyroid hormone sensitivity indices with the risks of NAFLD and related metabolic disorders. The correlation between thyroid hormone sensitivity and the severity of liver fibrosis evaluated by noninvasive fibrosis indices was analyzed through ordinal logistic regression.
Results: Euthyroid adults with NAFLD had elevated levels of serum FT3 and FT4, reduced TSH, and impaired sensitivity to thyroid hormones. Compared with participants in the first quartile group, the risk of NAFLD was higher in the fourth quartile of TFQIFT3 (OR 1.25, 95% CI 1.13-1.39, P < 0.001) and FT3/FT4 (OR 1.45, 95% CI 1.32-1.60, P < 0.001) after adjusting for metabolic confounders. Among NAFLD patients, higher FT3/FT4 positively correlated with increased severity of liver fibrosis, with ORs per SD of 10.80 (95% CI 4.12-28.53, P < 0.001) for aminotransferase-to-platelet ratio index, 4.74 (95% CI 1.56-14.38, P = 0.006) for NAFLD fibrosis score and 3.21 (95% CI 1.02-10.08, P = 0.046) for fibrosis-4 index.
Conclusion: Impaired central sensitivity to FT3 and higher FT3/FT4 were associated with increased risks of NAFLD and related metabolic disorders. In patients with NAFLD, higher FT3/FT4 correlated with its progression to liver fibrosis. These findings might provide novel insight into the monitoring and evaluation of the risk of NAFLD and the severity of liver fibrosis.
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An international, peer-reviewed, open access, online journal. The journal is committed to the rapid publication of the latest laboratory and clinical findings in the fields of diabetes, metabolic syndrome and obesity research. Original research, review, case reports, hypothesis formation, expert opinion and commentaries are all considered for publication.
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