Skip to main content

Advertisement

SpringerLink
Log in

Insufficient evidence to support the clinical efficacy of selenium supplementation for patients with chronic autoimmune thyroiditis

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

Abstract

Background

This study critically reappraises the documentation on the clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis (AIT) with the goal of improving the normalization of the treatment of this disease.

Methods

A literature search was performed in the Medline, Embase, and Cochrane Library databases. Twenty-three trials conducted in adults with AIT comparing the efficacy of selenium with or without levothyroxine (LT4) versus placebo and/or LT4 were eligible. The assessed outcomes were primarily pooled using a random- or fixed effects model based on the results of the heterogeneity test. The quality of evidence was assessed per outcome.

Results

In LT4-treated populations, patients receiving selenium demonstrated lower thyroid peroxidase antibody (TPOAb) levels at 3 months (mean difference [MD], −236.88; 95% confidence interval [CI], −353.35 to −120.41; p < 0.0001), 6 months (MD, −407.17; 95% CI, −623.60 to −190.73; p = 0.0002), and 12 months (MD, −327.03; 95% CI, −613.78 to −40.28; p = 0.0254), while thyroglobulin antibody (TgAb) levels only decreased at 12 months. In non-LT4-treated population, the selenium group demonstrated significantly lower TPOAb levels after 3 months (MD, −203.07; 95% CI, −395.44 to −10.70; p = 0.0385) and 6 months (MD, −322.27; 95% CI, −597.50 to −47.04; p = 0.0217) but not after 12 months, while TgAb levels only decreased at 3 months. There was no significant change in thyroid stimulating hormone (TSH) levels. Lower thyroid echogenicity was observed in all patients receiving selenium at 3, 6, and 12 months. However, these participants had a significantly higher risk of reported adverse effects.

Conclusions

Current evidence does not justify the emerging use of selenium supplementation in the treatment of AIT, despite it resulting in a decrease in autoantibody levels.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

AIT:

Autoimmune thyroiditis

LT4:

Levothyroxine

TgAb:

Thyroglobulin antibodies

TPOAb:

Thyroid peroxidase antibodies

TSH:

Thyrotropin

CXCL:

Serum chemokine ligand

TNF-α:

Tumor necrosis factor alpha

INF-γ:

Interferon gamma

IL:

Interleukin

MCP:

Monocyte chemoattractant protein

References

  1. R. Krysiak, K. Kowalcze, B. Okopień, Selenomethionine potentiates the impact of vitamin D on thyroid autoimmunity in euthyroid women with Hashimoto’s thyroiditis and low vitamin D status. Pharmacol. Rep. 71(2), 367–373 (2019). https://doi.org/10.1016/j.pharep.2018.12.006

    Article  CAS  PubMed  Google Scholar 

  2. W. Wang, J. Mao, J. Zhao, J. Lu, L. Yan, J. Du, Z. Lu, H. Wang, M. Xu, X. Bai, L. Zhu, C. Fan, H. Wang, H. Zhang, Z. Shan, W. Teng, Decreased thyroid peroxidase antibody titer in response to selenium supplementation in autoimmune thyroiditis and the influence of a selenoprotein P gene polymorphism: a prospective, multicenter study in China. Thyroid 28(12), 1674–1681 (2018). https://doi.org/10.1089/thy.2017.0230

    Article  CAS  PubMed  Google Scholar 

  3. J. Wichman, K.H. Winther, S.J. Bonnema, L. Hegedüs, Selenium supplementation significantly reduces thyroid autoantibody levels in patients with chronic autoimmune thyroiditis: a systematic review and meta-analysis. Thyroid 26(12), 1681–1692 (2016)

    Article  CAS  Google Scholar 

  4. T.H. Brix, K.O. Kyvik, L. Hegedüs, A population-based study of chronic autoimmune hypothyroidism in Danish twins. J. Clin. Endocrinol. Metab. 85(2), 536–539 (2000)

    CAS  PubMed  Google Scholar 

  5. T.G.A. Strieder, M.F. Prummel, J.G.P. Tijssen, E. Endert, W.M. Wiersinga, Risk factors for and prevalence of thyroid disorders in a cross-sectional study among healthy female relatives of patients with autoimmune thyroid disease. Clin. Endocrinol. 59(3), 396–401 (2003)

    Article  Google Scholar 

  6. L. Schomburg, J. Köhrle, On the importance of selenium and iodine metabolism for thyroid hormone biosynthesis and human health. Mol. Nutr. Food Res. 52(11), 1235–1246 (2008). https://doi.org/10.1002/mnfr.200700465

    Article  CAS  PubMed  Google Scholar 

  7. K.H. Winther, M.P. Rayman, S.J. Bonnema, L. Hegedüs, Selenium in thyroid disorders - essential knowledge for clinicians. Nat. Rev. Endocrinol. 16(3), 165–176 (2020). https://doi.org/10.1038/s41574-019-0311-6

    Article  CAS  PubMed  Google Scholar 

  8. J.K. Wrobel, R. Power, M. Toborek, Biological activity of selenium: revisited. IUBMB Life 68(2) (2016). https://doi.org/10.1002/iub.1466

  9. L.H. Duntas, S. Benvenga, Selenium: an element for life. Endocrine 48(3), 756–775 (2015). https://doi.org/10.1007/s12020-014-0477-6

    Article  CAS  PubMed  Google Scholar 

  10. E.A. Jensen, P.H. Petersen, O. Blaabjerg, P.S. Hansen, T.H. Brix, L. Hegedüs, Establishment of reference distributions and decision values for thyroid antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and the thyrotropin receptor (TRAb). Clin. Chem. Lab. Med. 44(8), 991–998 (2006)

    Article  CAS  Google Scholar 

  11. K.H. Winther, J.E.M. Wichman, S.J. Bonnema, L. Hegedüs, Insufficient documentation for clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis, based on a systematic review and meta-analysis. Endocrine 55(2), 376–385 (2017). https://doi.org/10.1007/s12020-016-1098-z

    Article  CAS  PubMed  Google Scholar 

  12. L. Yu, L. Zhou, E. Xu, Y. Bi, X. Hu, X. Pei, G. Jin, Levothyroxine monotherapy versus levothyroxine and selenium combination therapy in chronic lymphocytic thyroiditis. J. Endocrinol. Investig. 40(11), 1243–1250 (2017). https://doi.org/10.1007/s40618-017-0693-z

    Article  CAS  Google Scholar 

  13. F. Karimi, G.R. Omrani, Effects of selenium and vitamin C on the serum level of antithyroid peroxidase antibody in patients with autoimmune thyroiditis. J. Endocrinol. Investig. 42(4), 481–487 (2019). https://doi.org/10.1007/s40618-018-0944-7

    Article  CAS  Google Scholar 

  14. D. Esposito, M. Rotondi, G. Accardo, G. Vallone, G. Conzo, G. Docimo, F. Selvaggi, C. Cappelli, L. Chiovato, D. Giugliano, D. Pasquali, Influence of short-term selenium supplementation on the natural course of Hashimoto’s thyroiditis: clinical results of a blinded placebo-controlled randomized prospective trial. J. Endocrinol. Investig. 40(1), 83–89 (2017). https://doi.org/10.1007/s40618-016-0535-4

    Article  CAS  Google Scholar 

  15. A. Kachouei, H. Rezvanian, M. Amini, A. Aminorroaya, E. Moradi, The effect of levothyroxine and selenium versus levothyroxine alone on reducing the level of anti-thyroid peroxidase antibody in autoimmune hypothyroid patients. Adv. Biomed. Res. 7, 1 (2018). https://doi.org/10.4103/2277-9175.223735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. I. Pirola, E. Gandossi, B. Agosti, A. Delbarba, C. Cappelli, Selenium supplementation could restore euthyroidism in subclinical hypothyroid patients with autoimmune thyroiditis. Endokrynol. Pol. 67(6), 567–571 (2016). https://doi.org/10.5603/EP.2016.0064

    Article  CAS  PubMed  Google Scholar 

  17. H. Balshem, M. Helfand, H.J. Schünemann, A.D. Oxman, R. Kunz, J. Brozek, G.E. Vist, Y. Falck-Ytter, J. Meerpohl, S. Norris, G.H. Guyatt, GRADE guidelines: 3. rating the quality of evidence. J. Clin. Epidemiol. 64(4), 401–406 (2011). https://doi.org/10.1016/j.jclinepi.2010.07.015

    Article  PubMed  Google Scholar 

  18. J.P. Higgins, S. Green, Cochrane handbook for systematic reviews of interventions version 5.0.0. Naunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie 5(2), S38 (2008)

    Google Scholar 

  19. J.P.T. Higgins, S.G. Thompson, J.J. Deeks, D.G. Altman, Measuring inconsistency in meta-analyses. Bmj 327(7414), 557–560 (2003)

    Article  Google Scholar 

  20. E.E. Mazokopakis, J.A. Papadakis, M.G. Papadomanolaki, A.G. Batistakis, T.G. Giannakopoulos, E.E. Protopapadakis, E.S. Ganotakis, Effects of 12 months treatment with L-selenomethionine on serum anti-TPO Levels in Patients with Hashimoto’s thyroiditis. Thyroid 17(7), 609–612 (2007)

    Article  CAS  Google Scholar 

  21. D. Nacamulli, C. Mian, D. Petricca, F. Lazzarotto, S. Barollo, D. Pozza, S. Masiero, D. Faggian, M. Plebani, M.E. Girelli, F. Mantero, C. Betterle, Influence of physiological dietary selenium supplementation on the natural course of autoimmune thyroiditis. Clin. Endocrinol. 73(4), 535–539 (2010). https://doi.org/10.1111/j.1365-2265.2009.03758.x

    Article  CAS  Google Scholar 

  22. J. Kvicala, H.P. Zamrazil, V: Affects selenium indeed concentrations of serum autoantibodies TPOAb and TGAb? Trace Elem. Electrol. 27, 167 (2010)

    Article  Google Scholar 

  23. L.H. Duntas, E. Mantzou, D.A. Koutras, Effects of a six month treatment with selenomethionine in patients with autoimmune thyroiditis. Eur. J. Endocrinol. 148(4), 389–393 (2003)

    Article  CAS  Google Scholar 

  24. C.R. de Farias, B.R. Cardoso, G.M.B. de Oliveira, I.C. de Mello Guazzelli, R.M. Catarino, M.C. Chammas, S.M.F. Cozzolino, M. Knobel, A randomized-controlled, double-blind study of the impact of selenium supplementation on thyroid autoimmunity and inflammation with focus on the GPx1 genotypes. J. Endocrinol. Investig. 38(10), 1065–1074 (2015). https://doi.org/10.1007/s40618-015-0285-8

    Article  CAS  Google Scholar 

  25. T. Pilli, S. Cantara, L. Schomburg, V. Cenci, S. Cardinale, E.C.D. Heid, E.C. Kühn, G. Cevenini, F. Sestini, C. Fioravanti, G. D’Hauw, F. Pacini, IFNγ-inducible chemokines decrease upon selenomethionine supplementation in women with euthyroid autoimmune thyroiditis: comparison between two doses of selenomethionine (80 or 160 μg) versus placebo. Eur. Thyroid J. 4(4), 226–233 (2015). https://doi.org/10.1159/000439589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. S.A. Eskes, E. Endert, E. Fliers, E. Birnie, B. Hollenbach, L. Schomburg, J. Köhrle, W.M. Wiersinga, Selenite supplementation in euthyroid subjects with thyroid peroxidase antibodies. Clin. Endocrinol. 80(3), 444–451 (2014). https://doi.org/10.1111/cen.12284

    Article  CAS  Google Scholar 

  27. R. Krysiak, B. Okopien, Haemostatic effects of levothyroxine and selenomethionine in euthyroid patients with Hashimoto’s thyroiditis. Thromb. Haemost. 108(5), 973–980 (2012). https://doi.org/10.1160/TH12-04-0275

    Article  CAS  PubMed  Google Scholar 

  28. R. Krysiak, B. Okopien, The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto’s thyroiditis. J. Clin. Endocrinol. Metab. 96(7), 2206–2215 (2011). https://doi.org/10.1210/jc.2010-2986

    Article  CAS  PubMed  Google Scholar 

  29. C. Balázs, The effect of selenium therapy on autoimmune thyroiditis. Orv. Hetil. 149(26), 1227–1232 (2008)

    Article  Google Scholar 

  30. A.K. Bhuyan, D. Sarma, U.K. Saikia, Selenium and the thyroid: a close-knit connection. Indian J. Endocrinol. Metab. 16(Suppl 2), S354–S355 (2012). https://doi.org/10.4103/2230-8210.104090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. G. Karanikas, M. Schuetz, S. Kontur, H. Duan, S. Kommata, R. Schoen, A. Antoni, K. Kletter, R. Dudczak, M. Willheim, No immunological benefit of selenium in consecutive patients with autoimmune thyroiditis. Thyroid 18(1) (2008). https://doi.org/10.1089/thy.2007.0127

  32. O. Turker, K. Kumanlioglu, I. Karapolat, I. Dogan, Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses. J. Endocrinol. 190(1), 151–156 (2006)

    Article  CAS  Google Scholar 

  33. R. Gärtner, B.C.H. Gasnier, J.W. Dietrich, B. Krebs, M.W.A. Angstwurm, Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. J. Clin. Endocrinol. Metab. 87(4), 1687–1691 (2002)

    Article  Google Scholar 

  34. A.D. Anastasilakis, K.A. Toulis, P. Nisianakis, D.G. Goulis, L. Kampas, R.M. Valeri, D. Oikonomou, T.G. Tzellos, S. Delaroudis, Selenomethionine treatment in patients with autoimmune thyroiditis: a prospective, quasi-randomised trial. Int. J. Clin. Pract. 66(4), 378–383 (2012). https://doi.org/10.1111/j.1742-1241.2011.02879.x

    Article  CAS  PubMed  Google Scholar 

  35. R. Gärtner, B.C.H. Gasnier, Selenium in the treatment of autoimmune thyroiditis. BioFactors (Oxford, England) 19(3-4), 165–170 (2003)

    Article  Google Scholar 

  36. G.H. Guyatt, A.D. Oxman, R. Kunz, D. Atkins, J. Brozek, G. Vist, P. Alderson, P. Glasziou, Y. Falck-Ytter, H.J. Schünemann, GRADE guidelines: 2. Framing the question and deciding on important outcomes. J. Clin. Epidemiol. 64(4), 395–400 (2011). https://doi.org/10.1016/j.jclinepi.2010.09.012

    Article  PubMed  Google Scholar 

  37. J.P. Higgins, S.G. Thompson, J.J. Deeks, D.G. Altman, Measuring inconsistency in meta-analyses. Bmj 327(7414), 557–560 (2003). https://doi.org/10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

  38. K.A. Toulis, A.D. Anastasilakis, T.G. Tzellos, D.G. Goulis, D. Kouvelas, Selenium supplementation in the treatment of Hashimoto’s thyroiditis: a systematic review and a meta-analysis. Thyroid 20(10), 1163–1173 (2010). https://doi.org/10.1089/thy.2009.0351

    Article  CAS  PubMed  Google Scholar 

  39. L. Hegedüs, J.M. Hansen, U. Feldt-Rasmussen, B.M. Hansen, M. Høier-Madsen, Influence of thyroxine treatment on thyroid size and anti-thyroid peroxidase antibodies in Hashimoto’s thyroiditis. Clin. Endocrinol. 35(3), 235–238 (1991)

    Article  Google Scholar 

  40. M. Schmidt, M. Voell, I. Rahlff, M. Dietlein, C. Kobe, M. Faust, H. Schicha, Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) treated with levothyroxine. Thyroid 18(7), 755–760 (2008). https://doi.org/10.1089/thy.2008.0008

    Article  CAS  PubMed  Google Scholar 

  41. R.F. Burk, B.K. Norsworthy, K.E. Hill, A.K. Motley, D.W. Byrne, Effects of chemical form of selenium on plasma biomarkers in a high-dose human supplementation trial. Cancer Epidemiol. Biomarkers Prev. 15(4), 804–810 (2006)

    Article  CAS  Google Scholar 

  42. R.D. Grange, J.P. Thompson, D.G. Lambert, Radioimmunoassay, enzyme and non-enzyme-based immunoassays. Br. J. Anaesth. 112(2), 213–216 (2014). https://doi.org/10.1093/bja/aet293

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank American Journal Experts (AJE) very much for their help in editing the text.

Author contributions

Y.Q. and A.S. designed the study. Y.Q. and Z.X. performed the literature search. Q.X. and Q.Y. contributed to data acquisition. Y.Q. and Z.X. contributed to data interpretation and statistical analyses. Q.Y. and Q.X. contributed to supervision or mentorship. Y.Q. and Z.X. wrote the first draft of the paper. J.Z. and A.S. edited the report, and all authors contributed to the revision of the paper. All authors reviewed the paper, approved the final version, and agreed to submit it for publication.

Funding

This work was supported by the Sichuan Province Science and Technology Support Program (No. 2019YJ0038) and the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZY2017309).

Author information

Author notes

  1. These authors contributed equally: Yuxuan Qiu, Zhichao Xing

Authors and Affiliations

  1. Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China

    Yuxuan Qiu & Qianru Yang

  2. Center of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, China

    Yuxuan Qiu, Zhichao Xing, Jingqiang Zhu & Anping Su

  3. Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

    Qiao Xiang

Authors
  1. Yuxuan Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhichao Xing
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qiao Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qianru Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jingqiang Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anping Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anping Su.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

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

Qiu, Y., Xing, Z., Xiang, Q. et al. Insufficient evidence to support the clinical efficacy of selenium supplementation for patients with chronic autoimmune thyroiditis. Endocrine 73, 384–397 (2021). https://doi.org/10.1007/s12020-021-02642-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-021-02642-z

Keywords

Search

Navigation