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Horm Metab Res 2020; 52(09): 625-638
DOI: 10.1055/a-1199-2633
Review

Association Between Plasma Homocysteine Levels and Subclinical Hypothyroidism in Adult Subjects: A Meta-Analysis

Shou-Fa Zhang‡
1   Department of Internal Medicine, Shanghai Hudong Hospital, Shanghai, China
,
Li-Zhi Li‡
2   Department of Endocrinology, Yantai Hospital of Traditional Chinese Medicine, Yantai, China
,
Wei Zhang  ‡
3   Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China
,
Jin-Rong Guo
4   Department of Pharmacy, Hekou District Hospital of Traditional Chinese Medicine, Dongying, China
,
Fang-Fang Liu
5   QiLu Children’s Hospital of Shandong University, Jinan, China
,
Kai Ma
5   QiLu Children’s Hospital of Shandong University, Jinan, China
,
Shao-Hua Chen
3   Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China
,
Ya-Qing Zhang
6   Medical College of Northwest Minzu University, Lanzhou, China
› Author Affiliations Funding Information This study was supported by the Natural Science Foundation under Grant No. ZR2009CQ023 and Medical Science Development Plan of Shandong Province under Grant No. 2009QZ025.
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Abstract

Increased plasma homocysteine (Hcy) levels have been widely documented in patients with overt hypothyroidism; however, the significance of Hcy level changes in patients with subclinical hypothyroidism (SCH) remains controversial. The aim of this meta-analysis was to determine the Hcy status in patients with SCH compared with euthyroid subjects. We searched PubMed, Embase, and Cochrane Library databases prior to December 2019 to identify eligible studies and assessed the quality of selected studies using the Newcastle-Ottawa Quality Assessment Scale. Publication bias was evaluated by Begg’s test and Egger’s test. Meta-regression analysis was conducted to investigate the source of heterogeneity. A likely source of heterogeneity was the year of the study. All statistical analyses were performed with RevMan 5.3 and Stata 12.0 software. Our meta-analysis of twelve observational studies with 684 patients showed that those with SCH aged between 18 and 65 years old were associated with a slightly increased plasma Hcy level compared with euthyroid controls. The pooled result of the weighted mean difference (WMD) of increased tHcy levels was 1.16 μmol/l (95% CI: 0.51, 1.82; p=0.0005). The Hcy level in patients with SCH aged between 18 and 65 years old is significantly increased compared to euthyroid controls.

Key words

Subclinical hypothyroidism - hyperhomocysteinemia - cardiovascular disease - meta-analysis


Publication History

Received: 08 May 2020

Accepted: 04 June 2020

Article published online:
06 July 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Biondi B, Cappola AR, Cooper DS. Subclinical hypothyroidism: A review. JAMA 2019; 322: 153-160
    CrossrefPubMedGoogle Scholar
  • 2 Delitala AP, Scuteri A, Maioli M. et al. Subclinical hypothyroidism and cardiovascular risk factors. Minerva Med 2019; 110: 530-545
    PubMedGoogle Scholar
  • 3 Sert A, Pirgon O, Aypar E. et al. Subclinical hypothyroidism as a risk factor for the development of cardiovascular disease in obese adolescents with nonalcoholic fatty liver disease. Pediatr Cardiol 2013; 34: 1166-1174
    CrossrefPubMedGoogle Scholar
  • 4 Asvold BO, Bjøro T, Platou C. et al. Thyroid function and the risk of coronary heart disease: 12-year follow-up of the HUNT study in Norway. Clin Endocrinol (Oxf) 2012; 77: 911-917
    CrossrefPubMedGoogle Scholar
  • 5 Gao N, Zhang W, Zhang YZ. et al. Carotid intima-media thickness in patients with subclinical hypothyroidism: A meta-analysis. Atherosclerosis 2013; 227: 18-25
    CrossrefPubMedGoogle Scholar
  • 6 Rosário PWS, Calsolari MR. Subclinical hypothyroidism with TSH>7 mIU/l and ≤10 mIU/l and coronary artery disease. Horm Metab Res 2020; 52: 85-88
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Jabbar A, Pingitore A, Pearce SH. et al. Thyroid hormones and cardiovascular disease. Nat Rev Cardiol 2017; 14: 39-55
    CrossrefPubMedGoogle Scholar
  • 8 Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J 2015; 14: 6
    CrossrefPubMedGoogle Scholar
  • 9 Orzechowska-Pawilojc A, Sworczak K, Lewczuk A. et al. Homocysteine, folate and cobalamin levels in hypothyroid women before and after treatment. Endocr J 2007; 54: 471-476
    CrossrefPubMedGoogle Scholar
  • 10 Yang N, Yao Z, Miao L. et al. Novel clinical evidence of an Association between homocysteine and insulin resistance in patients with hypothyroidism or subclinical hypothyroidism. PLoS One 2015; 10: e0125922
    CrossrefPubMedGoogle Scholar
  • 11 Adrees M, Gibney J, El-Saeity N. et al. Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism. Clin Endocrinol (Oxf) 2009; 71: 298-303
    CrossrefPubMedGoogle Scholar
  • 12 Gunduz M, Gunduz E, Kircelli F. et al. Role of surrogate markers of atherosclerosis in clinical and subclinical thyroidism. Int J Endocrinol 2012; 109797
    PubMedGoogle Scholar
  • 13 Ebrahimpour A, Vaghari-Tabari M, Qujeq D. et al. Direct correlation between serum homocysteine level and insulin resistance index in patients with subclinical hypothyroidism: Does subclinical hypothyroidism increase the risk of diabetes and cardiovascular disease together?. Diabetes Metab Syndr 2018; 12: 863-867
    CrossrefPubMedGoogle Scholar
  • 14 Dong X, Yao Z, Hu Y. et al. Potential harmful correlation between homocysteine and low-density lipoprotein cholesterol in patients with hypothyroidism. Medicine (Baltimore) 2016; 95: e4291
    CrossrefPubMedGoogle Scholar
  • 15 Vayá A, Giménez C, Sarnago A. et al. Subclinical hypothyroidism and cardiovascular risk. Clin Hemorheol Microcirc 2014; 58: 1-7
    CrossrefPubMedGoogle Scholar
  • 16 Cakal B, Cakal E, Demirbaş B. et al. Homocysteine and fibrinogen changes with L-thyroxine in subclinical hypothyroid patients. J Korean Med Sci 2007; 22: 431-435
    CrossrefPubMedGoogle Scholar
  • 17 Luboshitzky R, Aviv A, Herer P. et al. Risk factors for cardiovascular disease in women with subclinical hypothyroidism. Thyroid 2002; 12: 421-425
    CrossrefPubMedGoogle Scholar
  • 18 Aldasouqi S, Nkansa-Dwamena D, Bokhari S. et al. Is subclinical hypothyroidism associated with hyperhomocysteinemia?. Endocr Pract 2004; 10: 399-403
    CrossrefPubMedGoogle Scholar
  • 19 Luboshitzky R, Herer P. Cardiovascular risk factors in middle-aged women with subclinical hypothyroidism. Neuro Endocrinol Lett 2004; 25: 262-266
    PubMedGoogle Scholar
  • 20 Erdal M, Sahin M, Saglam K. et al. Increased serum chitotriosidase activity following restoration of euthyroidism in patients with subclinical hypothyroidism. Intern Med 2008; 47: 1309-1314
    CrossrefPubMedGoogle Scholar
  • 21 Turhan S, Sezer S, Erden G. et al. Plasma homocysteine concentrations and serum lipid profile as atherosclerotic risk factors in subclinical hypothyroidism. Ann Saudi Med 2008; 28: 96-101
    CrossrefPubMedGoogle Scholar
  • 22 Stroup DF, Berlin JA, Morton SC. et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283: 2008-2012
    Google Scholar
  • 23 Higgins JP, Thompson SG, Deeks JJ. et al. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560
    Google Scholar
  • 24 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188
    CrossrefPubMedGoogle Scholar
  • 25 Djuric D, Jakovljevic V, Zivkovic V. et al. Homocysteine and homocysteine-related compounds: An overview of the roles in the pathology of the cardiovascular and nervous systems. Can J Physiol Pharmacol 2018; 96: 991-1003
    CrossrefPubMedGoogle Scholar
  • 26 Zhu M, Mao M, Lou X. Elevated homocysteine level and prognosis in patients with acute coronary syndrome: A meta-analysis. Biomarkers 2019; 24: 309-316
    CrossrefPubMedGoogle Scholar
  • 27 Chrysant SG, Chrysant GS. The current status of homocysteine as a risk factor for cardiovascular disease: a mini review. Expert Rev Cardiovasc Ther 2018; 16: 559-565
    CrossrefPubMedGoogle Scholar
  • 28 Collet TH, Gussekloo J, Bauer DC. et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med 2012; 172: 799-809
    CrossrefPubMedGoogle Scholar
  • 29 Chaker L, Baumgartner C, den Elzen WP. et al. Subclinical hypothyroidism and the risk of stroke events and fatal stroke: An individual participant data analysis. J Clin Endocrinol Metab 2015; 100: 2181-2191
    CrossrefPubMedGoogle Scholar
  • 30 Pasqualetti G, Tognini S, Polini A. et al. Is subclinical hypothyroidism a cardiovascular risk factor in the elderly?. J Clin Endocrinol Metab 2013; 98: 2256-2266
    CrossrefPubMedGoogle Scholar
  • 31 Moll S, Varga EA. Homocysteine and MTHFR Mutations. Circulation 2015; 132: e6-e9
    CrossrefPubMedGoogle Scholar
  • 32 Williams KT, Schalinske KL. Homocysteine metabolism and its relation to health and disease. Biofactors 2010; 36: 19-24
    PubMedGoogle Scholar
  • 33 Bamashmoos SA, Al-Nuzaily MA, Al-Meeri AM. et al. Relationship between total homocysteine, total cholesterol and creatinine levels in overt hypothyroid patients. Springerplus 2013; 2: 423
    CrossrefPubMedGoogle Scholar
  • 34 Zhang W, Tian LM, Han Y. et al. Presence of thyrotropin receptor in hepatocytes: Not a case of illegitimate transcription. J Cell Mol Med 2009; 13: 4636-4642
    CrossrefPubMedGoogle Scholar
  • 35 Li WX, Lv WW, Dai SX. et al. Joint associations of folate, homocysteine and MTHFR, MTR and MTRR gene polymorphisms with dyslipidemia in a Chinese hypertensive population: A cross-sectional study. Lipids Health Dis 2015; 14: 101
    CrossrefPubMedGoogle Scholar