Hypothyroidism-Associated Dyslipidemia: Potential Molecular Mechanisms Leading to NAFLD
Abstract
:1. Introduction
2. Thyroid Hormones and Thyroid Hormone Receptors
3. Thyroid Hormone Effects on Lipid Metabolism in the Liver and the Adipose Tissue
4. Thyroid Hormones and Dyslipidemia
5. NAFLD and Dysregulated Lipid Metabolism
6. Hypothyroidism and NAFLD: Clinical Studies
7. Thyroid Hormone Analogues for Dyslipidemia Treatment
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Reference | Study Design | Study Sample | Diagnosis of NAFLD | Definition of Hypothyroidism | Main Findings |
---|---|---|---|---|---|
Liangpunsakul et al. 2003 [55] | Cross-sectional case-control study | 174 patients with NASH and 442 controls | Biopsy (all cases had NASH) | Self-reported use of levothyroxin | Hypothyroidism was independently associated with NASH (OR 2.30, 95% CI 1.20–4.20) |
Reddy et al. 2007 [56] | Case-control study | 54 patients with HCC of unknown etiology and 2 groups of controls (57 HCC patients with HCV and 49 HCC patients with alcoholic liver disease) | Biopsy or clinical and imaging criteria | TSH > 5 mIU/L, history of hypothyroidism | Hypothyroidism is significantly higher prevalent in subjects with HCC of unknown etiology compared to controls with viral or alcoholic HCC |
Silveira et al. 2009 [57] | Cross-sectional study | 97 patients with NAFLD | Biopsy | TSH > 5 mIU/L or < 0.3 mIU/L Total T4 > 12.5 μg/dL or < 5 μg/dL History of hyper/hypothyroidism | The prevalence of hypothyroidism in patients with NAFLD was 20% |
Xu et al. 2011 [58] | Cross-sectional study | 227 patients with NAFLD and 651 controls | Ultrasound | TSH > 4.5 mIU/L or < 0.5 mIU/L FT4 > 14.4 pmol/L or < 7.85 pmol/L | Patients with hypothyroidism are more likely to develop NAFLD (p < 0.001), FT4 is a risk factor for NAFLD (OR = 0.847, 95% CI: 0.743–0.966) |
Chung et al. 2012 [59] | Cross-sectional study | 2324 patients with hypothyroidism and 2324 controls | Ultrasound | Subclinical hypothyroidism: TSH > 4.1 mIU/L and normal FT4 Overt hypothyroidism: TSH > 4.1 mIU/L and FT4 < 0.7 ng/dL | Hypothyroidism is an independent risk factor for NAFLD (OR = 1.38, 95% CI: 1.17–1.67) |
Pagadala et al. 2012 [60] | Cross-sectional study | 233 patients with NAFLD and 430 controls | Biopsy | Clinical diagnosis and on thyroid replacement therapy | Prevalence of hypothyroidism was higher in NAFLD patients (21.1% vs. 9.5%, p < 0.001) |
Xu et al. 2012 [61] | Prospective case-control study | 327 patients with subclinical hypothyroidism and 327 controls | Ultrasound (15% developed NAFLD after 4.9 years median follow-up) | TSH > 4.5 mIU/L and normal FT4 levels | Subclinical hypothyroidism was independently associated with risk of developing NAFLD (HR 2.21, 95% CI: 1.42–3.44) |
Itterman et al. 2012 [62] | Population-based study | 3661 individuals without a self-reported history of thyroid or liver disease | Ultrasound (16.1% had NAFLD) | Subclinical hypothyroidism: TSH > 3 mIU/L and normal FT4 Overt hypothyroidism: TSH > 3 mIU/L and FT4 < 7 pmol/L | Hypothyroidism was not independently associated with NAFLD. FT4 levels were inversely associated with NAFLD in men (OR 0.04, 95% CI: 0.01–0.17]) and in women (OR 0.06, 95% CI:0.01–0.42) |
Eshraghian et al. 2013 [63] | Cross-sectional study | 832 individuals | Ultrasound (15.3% had NAFLD) | Subclinical hypothyroidism: TSH > 5.2 mIU/L and normal FT4 levels Overt hypothyroidism: TSH > 5.2 mIU/L and FT4 < 11.5 pmol/L | Subclinical hypothyroidism was not associated with NAFLD (OR 1.12, 95% CI: 0.51–2.46). Overt hypothyroidism was not associated with NAFLD (OR 0.87, 95% CI: 0.33–2.28) |
Posadas-Romero et al. 2014 [64] | Cross-sectional study | 753 adults | Computed tomography (31.1% with NAFLD) | Subclinical hypothyroidism: TSH > 4.5 mIU/L and normal FT4 | Subclinical hypothyroidism was not associated with NAFLD (OR 0.83, 95% CI: 0.55–1.25) |
Lee et al. 2015 [65] | Retrospective cohort study | 18,544 individuals | Ultrasound | Subclinical hypothyroidism: TSH > 4.2 mIU/L, normal FT4 Overt hypothyroidism: TSH > 4.2 mIU/L, FT4 < 10.97 ng/dL | NAFLD incidence did not differ significantly with thyroid hormonal status (Subclinical hypothyroidism: HR = 0.965, 95% CI = 0.814–1.143, p = 0.67; Overt hypothyroidism group: HR = 1.255, 95% CI = 0.830–1.899, p = 0.28) |
Parikh et al. 2015 [66] | Case-control study | 500 patients with NAFLD and 300 controls | Ultrasound | Subclinical hypothyroidism: TSH > 5.5 IU/mL and <10 IU/mL) Overt hypothyroidism: TSH > 10 IU/mL) | NAFLD was statistically significantly associated with hypothyroidism (OR: 14.94, 95% CI: 3.5–62.6) |
Ludwig et al. 2015 [67] | Cross-sectional, population-based study | 1276 individuals | Ultrasound (24.7% with NAFLD) | Subclinical hypothyroidism: TSH > 3.4 mIU/L and normal total T4 Overt hypothyroidism: TSH > 3.4 mIU/L and total T4 < 12.8 pmol/L | Hypothyroidism was not associated with NAFLD (OR 1.19 95% CI: 0.65–2.17) |
Bano et al. 2016 [68] | Longitudinal prospective cohort study | 9419 euthyroid adults | Ultrasound (12.9% developed incident NAFLD after 10 years of median follow-up) | Subclinical hypothyroidism: TSH > 4.0 mIU/L and normal FT4 Overt hypothyroidism: TSH > 4.0 mIU/L and FT4 < 10.9 pmol/L | Hypothyroidism was associated with a 1.24-fold higher NAFLD risk (95% CI: 1.01–1.53). NAFLD risk decreased gradually from hypothyroidism to hyperthyroidism (p for trend = 0.003). |
Kim et al. 2018 [69] | Cross-sectional study | 425 patients with NAFLD | Biopsy | Subclinical hypothyroidism: TSH > 4.5 mIU/L and normal FT4 | Subclinical hypothyroidism was independently associated with NASH (OR 1.61, 95% CI: 1.04–2.50) and advanced fibrosis (OR 2.23 95% CI: 1.18–4.23). |
Martinez Escude et al. 2020 [70] | Cross-sectional, retrospective population study | 10,116 adults | Ultrasound | Subclinical hypothyroidism: TSH > 4.94 UI/mL and normal T4 Overt hypothyroidism: elevated TSH and decreased T4 | Hypothyroidism is not associated with NAFLD (p = 0.631) |
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Mavromati, M.; Jornayvaz, F.R. Hypothyroidism-Associated Dyslipidemia: Potential Molecular Mechanisms Leading to NAFLD. Int. J. Mol. Sci. 2021, 22, 12797. https://doi.org/10.3390/ijms222312797
Mavromati M, Jornayvaz FR. Hypothyroidism-Associated Dyslipidemia: Potential Molecular Mechanisms Leading to NAFLD. International Journal of Molecular Sciences. 2021; 22(23):12797. https://doi.org/10.3390/ijms222312797
Chicago/Turabian StyleMavromati, Maria, and François R. Jornayvaz. 2021. "Hypothyroidism-Associated Dyslipidemia: Potential Molecular Mechanisms Leading to NAFLD" International Journal of Molecular Sciences 22, no. 23: 12797. https://doi.org/10.3390/ijms222312797