Meta-analytic evidence for increased low-grade systemic inflammation and oxidative stress in hypothyroid patients. Can levothyroxine replacement therapy mitigate the burden?

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.

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Data availability

Data are available from PubMed.

Code availability

Analyses were executed in R versión 3.6.3 by using meta, metafor and dmetar R packages. Scrips are available under request.

Abbreviations

CRP:

C-reactive protein

CV:

cardiovascular

HT:

hypothyroidism

LRT:

levothyroxine replacement therapy

MDA:

malondialdehyde

OHT:

overt hypothyroidism

SHT:

subclinical hypothyroidism

SMD:

standardized mean difference

TBARS:

thiobarbituric-acid-reactive substances

TSH:

thyrotropin or thyroid-stimulating hormone

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Tellechea, M.L. Meta-analytic evidence for increased low-grade systemic inflammation and oxidative stress in hypothyroid patients. Can levothyroxine replacement therapy mitigate the burden?. Endocrine (2020). https://doi.org/10.1007/s12020-020-02484-1

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Keywords

  • Hypothyroidism
  • Low-grade inflammation
  • Oxidative stress
  • C-reactive protein
  • Malondialdehyde
  • Meta-analysis