Meta-analytic evidence for increased low-grade systemic inflammation and oxidative stress in hypothyroid patients. Can l
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META-ANALYSIS
Meta-analytic evidence for increased low-grade systemic inflammation and oxidative stress in hypothyroid patients. Can levothyroxine replacement therapy mitigate the burden? Mariana L. Tellechea
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Received: 18 June 2020 / Accepted: 26 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose This series of meta-analyses were aimed to elucidate the impact of hypothyroidism on low-grade systemic inflammation and oxidative stress assessed by C-reactive protein (CRP) and malondialdehyde (MDA) respectively; and to evaluate the effect of levothyroxine replacement therapy (LRT) on those outcomes. Methods PubMed database and the key studies references were searched prior to March 3, 2020. Data on serum or plasma CRP and MDA levels in SHT (subclinical) and/or OHT (overt) hypothyroid patients and controls were extracted to compute overall standardized mean differences (SMD) by the random-effects model. Results A total of 93 studies were entered into analyses and ten main meta-analyses were performed. OHT (SMD = 0.72 [0.39; 1.04], k = 35), SHT (SMD = 1.58 [0.78; 2.38], k = 56) and even mild SHT (TSH < 10 mU/L, SMD = 2.19 [0.02; 4.37], k = 13) proved to have a detrimental effect on CRP levels. LRT showed a favorable effect on CRP levels, particularly in OHT (SMD = −0.30 [−0.57; −0.02], k = 17). Increased levels of MDA were also found, especially in OHT (SMD = 2.49 [0.66; 4.31], k = 13). LRT may also improve MDA levels; however future studies would further validate the advantageous effect of LRT in hypothyroidism. Heterogeneity primarily originated from different study designs and geographic locations. Conclusion Overall, these meta-analyses reveal that screening for hs-CRP and MDA in hypothyroid patients as simple biomarkers of low-grade systemic inflammation and oxidative stress may become a useful tool to identify those at increased risk who may benefit most from early interventions. Keywords Hypothyroidism Low-grade inflammation Oxidative stress C-reactive protein Malondialdehyde Meta-analysis ●
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Abbreviations CRP C-reactive protein CV cardiovascular HT hypothyroidism LRT levothyroxine replacement therapy MDA malondialdehyde
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OHT SHT SMD TBARS TSH
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overt hypothyroidism subclinical hypothyroidism standardized mean difference thiobarbituric-acid-reactive substances thyrotropin or thyroid-stimulating hormone
Introduction Supplementary information The online version of this article (https:// doi.org/10.1007/s12020-020-02484-1) contains supplementary material, which is available to authorized users. * Mariana L. Tellechea [email protected] 1
Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE) CONICET – FEI – División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, C1425EFD Buenos Aires, Argentina
Hypothyroidism (HT) is one of the most common endocrine diseases and causes multiple metabolic disorders and tissue damage [1]. The effects of thyroid dysfunction on the cardiovascular (CV) s
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