Metabolic, Inflammatory and Oxidative Alterations in Patients with Steatotic Liver Disease: Role of Subclinical Hypothyroidism
Main Article Content
Abstract
Background: Subclinical hypothyroidism has emerged as a potential contributor to the metabolic dysfunction-associated steatotic liver disease, particularly in individuals with coexisting hypertension.
Aims: To evaluate metabolic profiles, inflammatory markers, and oxidative stress parameters in hypertensive patients with metabolic dysfunction-associated steatotic liver disease, depending on the presence of concomitant subclinical hypothyroidism.
Methods: A total of 126 patients examined from 2019 to 2022 were divided into four groups: Group 1 – controls (n = 30); Group 2 – hypertensive patients with steatotic liver disease (n = 26); Group 3 – patients with hypertension and subclinical hypothyroidism (n = 18); and Group 4 – patients with all three conditions (n = 52). In Groups 3 and 4, thyroid-stimulating hormone (TSH) levels ranged from 4 to 10 mU/L. Anthropometric parameters, biochemical profile, inflammatory (C-reactive protein, CRP, tumor necrosis factor α, TNF-α), and oxidative stress markers (total hydroperoxide content, THP, total antioxidant activity, TAA) were assessed.
Results: The presence of subclinical hypothyroidism (in either Group 3 or 4) was associated with significantly higher hip circumference (p < 0.05), lower waist-to-hip ratio (p < 0.001), elevated levels of glycated hemoglobin (p < 0.05), CRP (p < 0.05), and TNF-α (p < 0.001). Significantly higher levels of non-high-density lipoprotein cholesterol (non-HDL-C) (p = 0.005) and low-density lipoprotein cholesterol (p = 0.028), total cholesterol (p = 0.021), aspartate aminotransferase (p = 0.01), alkaline phosphatase (p = 0.034), THP (p = 0.014), and lower levels of HDL-C (p = 0.027) and glomerular filtration rate (p = 0.048) were observed in Group 4 compared to Group 2. In Group 4, TSH levels were positively associated with glucose (p = 0.008), TNF-α (p < 0.001), and inversely associated with HDL-C (p < 0.001), glomerular filtration rate (p < 0.001), and TAA (p = 0.012). A significantly higher proportion had a high cardiovascular risk according to SCORE2 in Group 4 compared to Group 2 (p = 0.023).
Conclusion: Subclinical hypothyroidism significantly contributes to the cardiometabolic burden in hypertensive patients with metabolic dysfunction-associated steatotic liver disease. Even among patients with mild subclinical hypothyroidism, higher systemic inflammation, oxidative stress, impaired glucose control, and lipid dysregulation are observed.
Article Details
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
2. Kotseva K, De Backer G, De Bacquer D, et al. Primary prevention efforts are poorly developed in people at high cardiovascular risk: A report from the European Society of Cardiology EURObservational Research Programme EUROASPIRE V survey in 16 European countries. Eur J Prev Cardiol. 2021;28(4):370-379. doi: 10.1177/2047487320908698
3. Ansu Baidoo V, Knutson KL. Associations between circadian disruption and cardiometabolic disease risk: a review. Obesity (Silver Spring). 2023;31(3):615-624. doi: 10.1002/oby.23666
4. Pu S, Zhao B, Jiang Y, Cui X. Hypothyroidism/ subclinical hypothyroidism and metabolic dysfunction-associated steatotic liver disease: advances in mechanism and treatment. Lipids Health Dis. 2025;24(1):1-6. doi: 10.1186/s12944-025-02474-0
5. Yuan S, Ebrahimi F, Bergman D, et al. Thyroid dysfunction in MASLD: Results of a nationwide study. JHEP Rep. 2025;7(5):101369. doi: 10.1016/j.jhepr.2025.101369
6. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87(2):489-499. doi: 10.1210/jcem.87.2.8182
7. Wyne KL, Nair L, Schneiderman CP, et al. Hypothyroidism prevalence in the United States: a retrospective study combining national health and nutrition examination survey and claims data, 2009–2019. J Endocr Soc. 2023;7(1):bvac172. doi: 10.1210/jendso/bvac172
8. Mendes D, Alves C, Silverio N, Marques FB. Prevalence of undiagnosed hypothyroidism in Europe: a systematic review and meta-analysis. Eur Thyroid J. 2019;8(3):130-143. doi: 10.1159/000499751
9. Podavalenko AP, Goncharova OA, Pashchenko LS. Epidemiological analysis of hypothyroidism prevalence in Kharkiv region. Int Endocrinol J. 2019;15(1):32-37. doi: 10.22141/2224-0721.15.1.2019.158690
10. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). Obes Facts. 2024;17(4):374-443. doi: 10.1159/000539371
11. Wang X, Wang H, Yan L, et al. The positive association between subclinical hypothyroidism and newly-diagnosed hypertension is more explicit in female individuals younger than 65. Endocrinol Metab (Seoul). 2021;36(4):778-789. doi:10.3803/EnM.2021.1101
12. Møller S, Kimer N, Hove JD, Barløse M, Gluud LL. Cardiovascular disease and metabolic dysfunction-associated steatotic liver disease: pathophysiology and diagnostic aspects. Eur J Prev Cardiol. 2025:zwae306. doi:10.1093/eurjpc/zwae306
13. Tellechea ML. Meta-analytic evidence for increased low-grade systemic inflammation and oxidative stress in hypothyroid patients. Can levothyroxine replacement therapy mitigate the burden? Endocrine. 2021;72:62-71. doi:10.1007/s12020-020-02484-1
14. Wang P, Zhang W, Liu H. Research status of subclinical hypothyroidism promoting the development and progression of cardiovascular diseases. Front Cardiovasc Med. 2025;12:1527271. doi:10.3389/fcvm.2025.1527271
15. Alamdari DH, Paletas K, Pegiou T, Sarigianni M, Befani C, Koliakos G. A novel assay for the evaluation of the prooxidant–antioxidant balance, before and after antioxidant vitamin administration in type II diabetes patients. Clin Biochem. 2007;40(3-4):248-254. doi: 10.1016/j.clinbiochem.2006.10.017
16. Sun Q, He Y, Yang L. The association of thyroid stimulating hormone and body fat in adults. PLoS One. 2024;19(12):e0314704. doi:10.1371/journal.pone.0314704
17. Pingitore A, Gaggini M, Mastorci F, Sabatino L, Cordiviola L, Vassalle C. Metabolic Syndrome, Thyroid Dysfunction, and Cardiovascular Risk: The Triptych of Evil. Int J Mol Sci. 2024;25(19):10628. doi:10.3390/ijms251910628
18. Stoica RA, Ancuceanu R, Costache A, et al. Subclinical hypothyroidism has no association with insulin resistance indices in adult females: A case-control study. Exp Ther Med. 2021;22(3):1033. doi:10.3892/etm.2021.10465
19. Zaidi A, Elmghirbi W, Algdar A, Saleh H. Association Between Subclinical Hypothyroidism and HbA1c Levels in Non-Diabetic Patients: A Case-Control Study. Libyan Med J. 2024;16(2):106-110.
20. Yang W, Jin C, Wang H, Lai Y, Li J, Shan Z. Subclinical hypothyroidism increases insulin resistance in normoglycemic people. Front Endocrinol (Lausanne). 2023;14:1106968. doi:10.3389/fendo.2023.1106968
21. Chng CL, Goh GB, Yen PM. Metabolic and Functional Cross Talk Between the Thyroid and Liver. Thyroid. 2025;35(6):607-623. doi: 10.1089/thy.2025.0178
22. Shimizu Y, Kawashiri SY, Noguchi Y, et al. Effect of subclinical hypothyroidism on the association between hemoglobin A1c and reduced renal function: a prospective study. Diagnostics (Basel). 2022;12(2): 462. doi:10.3390/diagnostics12020462
23. Ratziu V, Scanlan TS, Bruinstroop E. Thyroid hormone receptor-β analogs for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH). J Hepatol. 2024;82(2):375-387. doi:10.1016/j.jhep.2024.10.018
24. Xu Q, Wang Y, Shen X, Zhang Y, Fan Q, Zhang W. The effect of subclinical hypothyroidism on coagulation and fibrinolysis: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2022;13:861746. doi:10.3389/fendo.2022.861746
25. Torres EM, Tellechea ML. Biomarkers of endothelial dysfunction and cytokine levels in hypothyroidism: a series of meta-analyses. Expert Rev Endocrinol Metab. 2025;20(2):119-128. doi:10.1080/17446651.2024.2438997
26. Ramanathan R, Patwa SA, Ali AH, Ibdah JA. Thyroid hormone and mitochondrial dysfunction: therapeutic implications for metabolic dysfunction-associated steatotic liver disease (MASLD). Cells. 2023;12(24):2806. doi:10.3390/cells12242806
27. Zhu P, Lao G, Chen C, Luo L, Gu J, Ran J. TSH levels within the normal range and risk of cardiovascular and all-cause mortality among individuals with diabetes. Cardiovasc Diabetol. 2022;21(1):254. doi:10.1186/s12933-022-01698-z
28. Loosen SH, Demir M, Kostev K, Luedde T, Roderburg C. Incidences of hypothyroidism and autoimmune thyroiditis are increased in patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2021;33(1S):e1008-e1012. doi: 10.1097/MEG.0000000000002136
29. Wang S, Xia D, Fan H, et al. Low thyroid function is associated with metabolic dysfunction‐associated steatotic liver disease. JGH Open. 2024;8(2):e13038. doi: 10.1002/jgh3.13038