Skip to main content

Advertisement

SpringerLink
Log in

Serum lipids are novel predictors for thyroid autoimmunity in the general population with normal TSH levels from a cross-sectional study

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Objective

Serum lipids have been shown to regulate inflammatory and immune processes, but little is known about their association with thyroid autoimmunity. This study aimed to investigate the association of serum lipids with thyroid autoantibody positivity in the general population with normal thyroid-stimulating hormone (TSH) levels.

Methods

Data regarding the 7688 subjects’ baseline characteristics were retrospectively collected. All subjects were categorized into four groups according to thyroid autoantibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) positivity and serum lipid levels were compared. Binary logistic regression models were used to evaluate the risk of TgAb or TPOAb positivity with increasing serum lipid levels.

Results

In 6456 included subjects, after adjusting for confounders, the risk of TgAb positivity was positively associated with increasing low-density lipoprotein cholesterol (LDL-C) levels (OR 1.14, 95% CI 1.03–1.27, P = 0.011) and negatively correlated with the increasing high-density lipoprotein cholesterol (HDL-C) levels (OR 0.77, 95% CI 0.61–0.98, P = 0.035). In female subjects, the association between increasing LDL-C (OR 1.16, 95% CI 1.04–1.28, P = 0.007) or HDL-C levels (OR 0.77, 95% CI 0.61–0.99, P = 0.037) and TgAb positivity become more pronounced.

Conclusion

We have shown the associations of HDL-C and LDL-C with TgAb positivity in the general population with normal TSH levels in a gender-dependent manner. This study highlights that serum lipids may be new predictors of thyroid autoimmunity even when TSH is within the reference range.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Y. Li, D. Teng, J. Ba, B. Chen, J. Du, L. He, X. Lai, X. Teng, X. Shi, Y. Li, H. Chi, E. Liao, C. Liu, L. Liu, G. Qin, Y. Qin, H. Quan, B. Shi, H. Sun, X. Tang, N. Tong, G. Wang, J.A. Zhang, Y. Wang, Y. Xue, L. Yan, J. Yang, L. Yang, Y. Yao, Z. Ye, Q. Zhang, L. Zhang, J. Zhu, M. Zhu, G. Ning, Y. Mu, J. Zhao, Z. Shan, W. Teng, Efficacy and Safety of Long-Term Universal Salt Iodization on Thyroid Disorders: Epidemiological Evidence from 31 Provinces of Mainland China. Thyroid 30(4), 568–579 (2020). https://doi.org/10.1089/thy.2019.0067

    Article  CAS  PubMed  Google Scholar 

  2. P.S. Fowler, J. Swale, Premyxoedema and coronary-artery disease. Lancet 1(7499), 1077–1079 (1967). https://doi.org/10.1016/s0140-6736(67)92650-5

    Article  CAS  PubMed  Google Scholar 

  3. G. Tamer, M. Mert, I. Tamer, B. Mesci, D. Kilic, S. Arik, Effects of thyroid autoimmunity on abdominal obesity and hyperlipidaemia. Endokrynol. Pol. 62(5), 421–428 (2011)

    CAS  PubMed  Google Scholar 

  4. T. Mazaheri, F. Sharifi, K. Kamali, Insulin resistance in hypothyroid patients under Levothyroxine therapy: a comparison between those with and without thyroid autoimmunity. J. Diabetes Metab. Disord. 13(1), 103 (2014). https://doi.org/10.1186/s40200-014-0103-4

    Article  PubMed  PubMed Central  Google Scholar 

  5. D. Kang, Q. Yin, X. Yan, H. Song, G. Gao, J. Liang, J. Zhao, Serum cholesterol levels in middle-aged euthyroid subjects with positive thyroid peroxidase antibodies. Int. J. Clin. Exp. Med. 8(11), 21623–21628 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Y. Chen, C. Zhu, Y. Chen, N. Wang, Q. Li, B. Han, L. Zhao, C. Chen, H. Zhai, L. Zhang, Y. Lu, Are thyroid autoimmune diseases associated with cardiometabolic risks in a population with normal thyroid-stimulating hormone? Mediators Inflamm. 2018, 1856137 (2018). https://doi.org/10.1155/2018/1856137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. V.K. Srivastava, H. Singh, Association of thyroid peroxidase antibody and dyslipidemia in subclinical hypothyroidism. J. Family Med. Prim. Care 6(1), 63–68 (2017). https://doi.org/10.4103/2249-4863.214958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. M.C. Madsen, V. Anette, B.G. Nordestgaard, Low HDL cholesterol and high risk of autoimmune disease: two population-based cohort studies including 117341 individuals. Clin. Chem. 65(5), 644–652 (2019). https://doi.org/10.1373/clinchem.2018.299636

    Article  CAS  PubMed  Google Scholar 

  9. M.B. Fessler, Regulation of adaptive immunity in health and disease by cholesterol metabolism. Curr. Allergy Asthma Rep. 15(8), 48 (2015). https://doi.org/10.1007/s11882-015-0548-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. A. Ito, C. Hong, K. Oka, J.V. Salazar, C. Diehl, J.L. Witztum, M. Diaz, A. Castrillo, S.J. Bensinger, L. Chan, P. Tontonoz, Cholesterol accumulation in CD11c immune cells is a causal and targetable factor in autoimmune disease. Immunity 45(6), 1311–1326 (2016). https://doi.org/10.1016/j.immuni.2016.11.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. J.D. Stein, D. Childers, S. Gupta, N. Talwar, B. Nan, B.J. Lee, T.J. Smith, R. Douglas, Risk factors for developing thyroid-associated ophthalmopathy among individuals with Graves disease. JAMA Ophthalmol. 133(3), 290–296 (2015). https://doi.org/10.1001/jamaophthalmol.2014.5103

    Article  PubMed  PubMed Central  Google Scholar 

  12. S. Gullu, R. Emral, M. Bastemir, A.B. Parkes, J.H. Lazarus, In vivo and in vitro effects of statins on lymphocytes in patients with Hashimoto’s thyroiditis. Eur. J. Endocrinol. 153(1), 41–48 (2005). https://doi.org/10.1530/eje.1.01941

    Article  CAS  PubMed  Google Scholar 

  13. X. Wu, M. Schott, C. Liu, C. Qian, X. Mao, K. Xu, J. Jiang, Y. Xu, M. Shen, C. Papewalis, W.A. Scherbaum, C. Liu, Statins decrease the aberrant HLA-DR expression on thyrocytes from patients with Hashimoto’s thyroiditis. Horm. Metab. Res. 40(12), 838–841 (2008). https://doi.org/10.1055/s-2008-1081500

    Article  CAS  PubMed  Google Scholar 

  14. R. Krysiak, W. Szkróbka, B. Okopień, The effect of hypolipidemic agents on thyroid autoimmunity in women with Hashimoto’s thyroiditis treated with levothyroxine and selenomethionine. Exp. Clin. Endocrinol. Diabetes 126(5), 321–326 (2018). https://doi.org/10.1055/s-0043-120342

    Article  CAS  PubMed  Google Scholar 

  15. Chinese Medical Association, Chinese Medical Journals Publishing House, Chinese Society of General Practice, Editorial Board of Chinese Journal of General Practitioners of Chinese Medical Association, Expert Group of Guidelines for Primary Care of CardiovascularDisease: Guideline for primary care of dyslipidemias. Chin. J. Gen. Pract. (05), 406–416 (2019). https://doi.org/10.3760/cma.j.issn.1671-7368.2019.05.004

  16. J. Zhang, Y. Gao, Y. Li, D. Teng, Y. Xue, L. Yan, J. Yang, L. Yang, Y. Yao, J. Ba, B. Chen, J. Du, L. He, X. Lai, X. Teng, X. Shi, Y. Li, H. Chi, E. Liao, C. Liu, L. Liu, G. Qin, Y Qin, H. Quan, B. Shi, H. Sun, X. Tang, N. Tong, G. Wang, J.A. Zhang, Y. Wang, Z. Ye, Q. Zhang, L. Zhang, J. Zhu, M Zhu, W. Teng, Z. Shan, J. Li, The Presence of Serum TgAb Suggests Lower Risks for Glucose and Lipid Metabolic Disorders in Euthyroid General Population From a National Survey. Front. Endocrinol. 11 (2020). https://doi.org/10.3389/fendo.2020.00139

  17. K. Tselios, C. Koumaras, D.D. Gladman, M.B. Urowitz, Dyslipidemia in systemic lupus erythematosus: just another comorbidity? Semin. Arthritis. Rheum. 45(5), 604–610 (2016). https://doi.org/10.1016/j.semarthrit.2015.10.010

    Article  CAS  PubMed  Google Scholar 

  18. V.L. Langén, T.J. Niiranen, P. Puukka, J. Sundvall, A.M. Jula, Association of thyroid-stimulating hormone with lipid concentrations: an 11-year longitudinal study. Clin. Endocrinol. 86(1), 120–127 (2017). https://doi.org/10.1111/cen.13151

    Article  CAS  Google Scholar 

  19. S. Santos-Palacios, A. Brugos-Larumbe, F. Guillén-Grima, J.C. Galofré, A cross-sectional study of the association between circulating TSH level and lipid profile in a large Spanish population. Clin. Endocrinol. 79(6), 874–881 (2013). https://doi.org/10.1111/cen.12216

    Article  CAS  Google Scholar 

  20. C. Xu, X. Yang, W. Liu, H. Yuan, C. Yu, L. Gao, J. Zhao, Thyroid stimulating hormone, independent of thyroid hormone, can elevate the serum total cholesterol level in patients with coronary heart disease: a cross-sectional design. Nutr. Metab. 9(1), 44 (2012). https://doi.org/10.1186/1743-7075-9-44

    Article  CAS  Google Scholar 

  21. D. Teng, W. Yang, X. Shi, Y. Li, J. Ba, B. Chen, J. Du, L. He, X. Lai, Y. Li, H. Chi, E. Liao, C. Liu, L. Liu, G. Qin, Y. Qin, H. Quan, B. Shi, H. Sun, X. Tang, N. Tong, G. Wang, J.A. Zhang, Y. Wang, Y. Xue, L. Yan, J. Yang, L. Yang, Y. Yao, Z. Ye, Q. Zhang, L. Zhang, J. Zhu, M. Zhu, Z. Shan, W. Teng, An inverse relationship between iodine intake and thyroid antibodies: a national cross-sectional survey in mainland China. Thyroid 30(11), 1656–1665 (2020). https://doi.org/10.1089/thy.2020.0037

    Article  CAS  PubMed  Google Scholar 

  22. B.J. Wells, W.J. Hueston, Are thyroid peroxidase antibodies associated with cardiovascular disease risk in patients with subclinical hypothyroidism? Clin. Endocrinol. 62(5), 580–584 (2005). https://doi.org/10.1111/j.1365-2265.2005.02262.x

    Article  CAS  Google Scholar 

  23. O. Topaloglu, F. Gokay, K. Kucukler, F.S. Burnik, T. Mete, H.C. Yavuz, D. Berker, S. Guler, Is autoimmune thyroiditis a risk factor for early atherosclerosis in premenopausal women even if in euthyroid status? Endocrine 44(1), 145–151 (2013). https://doi.org/10.1007/s12020-012-9842-5

    Article  CAS  PubMed  Google Scholar 

  24. C. Xiaodong, S. Jie, The study of the level of blood fat and the relationship between the level of thyroid autoimmune antibody in hyperthyroidism patients. Med. J. Commun. 30(2), 117–120 (2016)

    Google Scholar 

  25. L. Chai, X. Liu, Y. Ma, L. Zhang, L. Zheng, The study of the level of blood lipid and the relationship between thyroid hormone and autoantibody in AITD patients. Henan. Med. Res. 26(1), 25–28 (2017). https://doi.org/10.3969/j.issn.1004-437X.2017.01.009

    Article  Google Scholar 

  26. M. Hamer, G. O’Donovan, E. Stamatakis, High-density lipoprotein cholesterol and mortality: too much of a good thing? Arterioscler. Thromb. Vasc. Biol. 38(3), 669–672 (2018). https://doi.org/10.1161/ATVBAHA.117.310587

    Article  CAS  PubMed  Google Scholar 

  27. M.M. Motazacker, J. Peter, M. Treskes, C.C. Shoulders, J.A. Kuivenhoven, G.K. Hovingh, Evidence of a polygenic origin of extreme high-density lipoprotein cholesterol levels. Arterioscler. Thromb. Vasc. Biol. 33(7), 1521–1528 (2013). https://doi.org/10.1161/ATVBAHA.113.301505

    Article  CAS  PubMed  Google Scholar 

  28. Emerging Risk Factors Collaboration, E.D. Angelantonio, N. Sarwar, P. Perry, S. Kaptoge, K.K. Ray, A. Thompson, A.M. Wood, S. Lewington, N. Sattar, C.J. Packard, R. Collins, S.G. Thompson, J. Danesh, Major lipids, apolipoproteins, and risk of vascular disease. JAMA 302(18), 1993–2000 (2009). https://doi.org/10.1001/jama.2009.1619

    Article  Google Scholar 

  29. D.J. Gordon, J.L. Probstfield, R.J. Garrison, J.D. Neaton, W.P. Castelli, J.D. Knoke, D.R. Jacobs Jr., S. Bangdiwala, H.A. Tyroler, High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 79(1), 8–15 (1989). https://doi.org/10.1161/01.cir.79.1.8

    Article  CAS  PubMed  Google Scholar 

  30. Y. Wu, X. Shi, X. Tang, Y. Li, N. Tong, G. Wang, J.A. Zhang, Y. Wang, J. Ba, B. Chen, J. Du, L. He, X. Lai, Y. Li, H. Chi, E. Liao, C. Liu, L. Liu, G. Qin, Y. Qin, H. Quan, B. Shi, H. Sun, Y. Xue, L. Yan, J. Yang, L. Yang, Y. Yao, Z. Ye, Q. Zhang, L. Zhang, J. Zhu, M. Zhu, W. Teng, Z. Shan, The Correlation Between Metabolic Disorders And Tpoab/Tgab: A Cross-Sectional Population-Based Study. Endocr. Pract. 26(8), 869–882 (2020). https://doi.org/10.4158/ep-2020-0008

    Article  PubMed  Google Scholar 

  31. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 285(19), 2486–2497 (2001). https://doi.org/10.1001/jama.285.19.2486

  32. S. Amur, A. Parekh, P. Mummaneni, Sex differences and genomics in autoimmune diseases. J. Autoimmun. 38(2–3), J254–J265 (2012). https://doi.org/10.1016/j.jaut.2011.12.001

    Article  CAS  PubMed  Google Scholar 

  33. E.N. Fish, The X-files in immunity: sex-based differences predispose immune responses. Nat. Rev. Immunol. 8(9), 737–744 (2008). https://doi.org/10.1038/nri2394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. M. Sopori, Effects of cigarette smoke on the immune system. Nat. Rev. Immunol. 2(5), 372–377 (2002). https://doi.org/10.1038/nri803

    Article  CAS  PubMed  Google Scholar 

  35. Y.I. Miller, S. Viriyakosol, C.J. Binder, J.R. Feramisco, T.N. Kirkland, J.L. Witztum, Minimally modified LDL binds to CD14, induces macrophage spreading via TLR4/MD-2, and inhibits phagocytosis of apoptotic cells. J. Biol. Chem. 278(3), 1561–1568 (2003). https://doi.org/10.1074/jbc.M209634200

    Article  CAS  PubMed  Google Scholar 

  36. K.A. Dvornikova, E.Y. Bystrova, O.N. Platonova, L.P. Churilov, Polymorphism of toll-like receptor genes and autoimmune endocrine diseases. Autoimmun. Rev. 19(4), 102496 (2020). https://doi.org/10.1016/j.autrev.2020.102496

    Article  CAS  PubMed  Google Scholar 

  37. B.J. Wu, K.L. Ong, S. Shrestha, K. Chen, F. Tabet, P.J. Barter, K.A. Rye, Inhibition of arthritis in the Lewis rat by apolipoprotein A-I and reconstituted high-density lipoproteins. Arterioscler. Thromb. Vasc. Biol. 34(3), 543–551 (2014). https://doi.org/10.1161/ATVBAHA.113.302832

    Article  CAS  PubMed  Google Scholar 

  38. M. Suzuki, D.K. Pritchard, L. Becker, A.N. Hoofnagle, N. Tanimura, T.K. Bammler, R.P. Beyer, R. Bumgarner, T. Vaisar, M.C. de Beer, F.C. de Beer, K. Miyake, J.F. Oram, J.W. Heinecke, High-density lipoprotein suppresses the type I interferon response, a family of potent antiviral immunoregulators, in macrophages challenged with lipopolysaccharide. Circulation 122(19), 1919–1927 (2010). https://doi.org/10.1161/CIRCULATIONAHA.110.961193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. I. Ates, F.M. Yilmaz, M. Altay, N. Yilmaz, D. Berker, S. Güler, The relationship between oxidative stress and autoimmunity in Hashimoto’s thyroiditis. Eur. J. Endocrinol. 173(6), 791–799 (2015). https://doi.org/10.1530/EJE-15-0617

    Article  CAS  PubMed  Google Scholar 

  40. N. Hermida, J.L. Balligand, Low-density lipoprotein-cholesterol-induced endothelial dysfunction and oxidative stress: the role of statins. Antioxid. Redox Signal. 20(8), 1216–1237 (2014). https://doi.org/10.1089/ars.2013.5537

    Article  CAS  PubMed  Google Scholar 

  41. E. Xepapadaki, E. Zvintzou, C. Kalogeropoulou, S. Filou, K.E. Kypreos, Τhe antioxidant function of HDL in atherosclerosis. Angiology 71(2), 112–121 (2020). https://doi.org/10.1177/0003319719854609

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank all the participants of this study. We acknowledge Yongze Li, MD and PhD for his contribution in the statistical analyses. We also appreciate Di Wu, MBBS, for her help with editing the English language of the manuscript.

Funding

This work was supported by the National Natural and Science Foundation of China (grant number: 81870538).

Author information

Author notes

  1. These authors contributed equally: Jiarong Li, Zixiao Wang

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, China

    Jiarong Li, He Liu, Jinrong Fu & Fengye Qin

  2. Department of Physical Examination Center, The First Hospital of China Medical University, Shenyang, 110001, China

    Zixiao Wang & Wei Wang

  3. Department of Endocrinology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, Guangdong, 510080, PR China

    Haixia Guan

  4. The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510000, PR China

    Haixia Guan

Authors
  1. Jiarong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zixiao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. He Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jinrong Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fengye Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Haixia Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.G. and W.W. contributed to the study conception and design. Material preparation and data collection and analysis were performed by J.L., Z.W., H.L., J.F., and F.Q. The first draft of the manuscript was written by J.L. and Z.W. All authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Haixia Guan or Wei Wang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethics approval

This retrospective study was approved by the Medical Ethics Committee of The First Hospital of China Medical University. Informed consent waiver was obtained to use deidentified data.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, J., Wang, Z., Liu, H. et al. Serum lipids are novel predictors for thyroid autoimmunity in the general population with normal TSH levels from a cross-sectional study. Endocrine 73, 331–338 (2021). https://doi.org/10.1007/s12020-021-02731-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-021-02731-z

Keywords

Search

Navigation