A randomized-controlled, double-blind study of the impact of selenium supplementation on thyroid autoimmunity and inflammation with focus on the GPx1 genotypes

Abstract

Purpose

To analyze the impact of selenium supplementation on serum antiTPO levels and thyroid echogenicity in patients with CAT, evaluating the response in subgroups with different GPx1 genotypes.

Methods

CAT patients (n = 55) with positive antiTPO were randomized to selenomethionine (SeMet) 200 μg daily (n = 28) or placebo (n = 27) for 3 months. Assessments included GPx1 genotyping at baseline and serum levels of plasma selenium, erythrocyte GPx1 activity, antiTPO and thyroid echogenicity at baseline, and 3 and 6 months.

Results

In the SeMet group, the increase in plasma levels of selenium and erythrocyte GPx1 activity was similar among patients with different GPx1 genotypes. In the overall cohort, patients randomized to SeMet showed a 5 % decrease in antiTPO levels at 3 months (p = non-significant) and 20 % at 6 months (p < 0.001 versus 3 months). In contrast, patients in the placebo group did not show significant changes in antiTPO levels at any time point. Subgroup analysis showed that patients with different GPx1 genotypes presented comparable responses in antiTPO levels and echogenicity index to SeMet.

Conclusions

Selenium supplementation decreased serum antiTPO levels in CAT patients, with similar response among patients with different GPx1 genotypes.

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

Fig. 1
Fig. 2

References

  1. 1.

    Padberg S, Heller K, Usadel KH, Schumm-Draeger PM (2001) One-year prophylactic treatment of euthyroid Hashimoto’s thyroiditis patients with levothyroxine: is there a benefit? Thyroid 11(3):249–255

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Duntas LH (2008) Environmental factors and autoimmune thyroiditis. Nat Clin Pract Endocrinol Metab 4(8):454–460

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Pearce EN, Farwell AP, Braverman LE (2003) Thyroiditis. N Engl J Med 348(26):2646–2655

    Article  PubMed  Google Scholar 

  4. 4.

    Toulis KA, Anastasilakis AD, Tzellos TG, Goulis DG, Kouvelas D (2010) Selenium supplementation in the treatment of Hashimoto’s thyroiditis: a systematic review and a meta-analysis. Thyroid 20(10):1163–1173

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Petricca D, Nacamulli D, Mian C, Mantero F, Cavedon E, Girelli ME, Betterle C (2012) Effects of selenium supplementation on the natural course of autoimmune thyroiditis: a short review. J Endocrinol Invest 35(4):419–424

    CAS  PubMed  Google Scholar 

  6. 6.

    Gartner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm MW (2002) Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. J Clin Endocrinol Metab 87(4):1687–1691

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Gartner R, Gasnier BC (2003) Selenium in the treatment of autoimmune thyroiditis. Biofactors 19(3–4):165–170

    Article  PubMed  Google Scholar 

  8. 8.

    Duntas LH, Mantzou E, Koutras DA (2003) Effects of a six month treatment with selenomethionine in patients with autoimmune thyroiditis. Eur J Endocrinol 148(4):389–393

    CAS  Article  PubMed  Google Scholar 

  9. 9.

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

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H (2007) The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab 92(4):1263–1268

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Mazokopakis EE, Papadakis JA, Papadomanolaki MG, Batistakis AG, Giannakopoulos TG, Protopapadakis EE, Ganotakis ES (2007) Effects of 12 months treatment with l-selenomethionine on serum anti-TPO levels in patients with Hashimoto’s thyroiditis. Thyroid 17(7):609–612

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Karanikas G, Schuetz M, Kontur S, Duan H, Kommata S, Schoen R, Antoni A, Kletter K, Dudczak R, Willheim M (2008) No immunological benefit of selenium in consecutive patients with autoimmune thyroiditis. Thyroid 18(1):7–12

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Nacamulli D, Mian C, Petricca D, Lazzarotto F, Barollo S, Pozza D, Masiero S, Faggian D, Plebani M, Girelli ME, Mantero F, Betterle C (2010) Influence of physiological dietary selenium supplementation on the natural course of autoimmune thyroiditis. Clin Endocrinol (Oxf) 73(4):535–539

    CAS  Google Scholar 

  14. 14.

    Bonfig W, Gartner R, Schmidt H (2010) Selenium supplementation does not decrease thyroid peroxidase antibody concentration in children and adolescents with autoimmune thyroiditis. Sci World J 10:990–996

    CAS  Article  Google Scholar 

  15. 15.

    Krysiak R, Okopien B (2011) 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

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Anastasilakis AD, Toulis KA, Nisianakis P, Goulis DG, Kampas L, Valeri RM, Oikonomou D, Tzellos TG, Delaroudis S (2012) Selenomethionine treatment in patients with autoimmune thyroiditis: a prospective, quasi-randomised trial. Int J Clin Pract 66(4):378–383

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Eskes SA, Endert E, Fliers E, Birnie E, Hollenbach B, Schomburg L, Kohrle J, Wiersinga WM (2014) Selenite supplementation in euthyroid subjects with thyroid peroxidase antibodies. Clin Endocrinol (Oxf) 80(3):444–451

    CAS  Article  Google Scholar 

  18. 18.

    Duntas LH, Benvenga S (2015) Selenium: an element for life. Endocrine 48(3):756–775

  19. 19.

    Jablonska E, Gromadzinska J, Reszka E, Wasowicz W, Sobala W, Szeszenia-Dabrowska N, Boffetta P (2009) Association between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans. Eur J Nutr 48(6):383–386

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Rago T, Chiovato L, Grasso L, Pinchera A, Vitti P (2001) Thyroid ultrasonography as a tool for detecting thyroid autoimmune diseases and predicting thyroid dsfunction in apparently healthy subjects. J Endocrinol Invest 24(10):763–769

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Muller HW, Schroder S, Schneider C, Seifert G (1985) Sonographic tissue characterisation in thyroid gland diagnosis. A correlation between sonography and histology. Klin Wochenschr 63(15):706–710

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Mazziotti G, Sorvillo F, Iorio S, Carbone A, Romeo A, Piscopo M, Capuano S, Capuano E, Amato G, Carella C (2003) Grey-scale analysis allows a quantitative evaluation of thyroid echogenicity in the patients with Hashimoto’s thyroiditis. Clin Endocrinol (Oxf) 59(2):223–229

    Article  Google Scholar 

  23. 23.

    Loy M, Cianchetti ME, Cardia F, Melis A, Boi F, Mariotti S (2004) Correlation of computerized gray-scale sonographic findings with thyroid function and thyroid autoimmune activity in patients with Hashimoto’s thyroiditis. J Clin Ultrasound 32(3):136–140

    Article  PubMed  Google Scholar 

  24. 24.

    Hao DQ, Xie GH, Zhang YM, Tian GJ (1996) Determination of serum selenium by hydride generation flame atomic absorption spectrometry. Talanta 43(4):595–600

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70(1):158–169

    CAS  PubMed  Google Scholar 

  26. 26.

    Als C, Helbling A, Peter K, Haldimann M, Zimmerli B, Gerber H (2000) Urinary iodine concentration follows a circadian rhythm: a study with 3023 spot urine samples in adults and children. J Clin Endocrinol Metab 85(4):1367–1369

    CAS  PubMed  Google Scholar 

  27. 27.

    Sandell EB, Kolthoff IM (1937) Micro-determination of iodine by a catalytic method. Microchem Acta 1:9–25

    CAS  Article  Google Scholar 

  28. 28.

    Pino S, Fang SL, Braverman LE (1996) Ammonium persulfate: a safe alternative oxidizing reagent for measuring urinary iodine. Clin Chem 42(2):239–243

    CAS  PubMed  Google Scholar 

  29. 29.

    Brunn J, Block U, Ruf G, Bos I, Kunze WP, Scriba PC (1981) Volumetric analysis of thyroid lobes by real-time ultrasound (author’s transl). Dtsch Med Wochenschr 106(41):1338–1340

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Hofling DB, Chavantes MC, Juliano AG, Cerri GG, Knobel M, Yoshimura EM, Chammas MC (2013) Low-level laser in the treatment of patients with hypothyroidism induced by chronic autoimmune thyroiditis: a randomized, placebo-controlled clinical trial. Lasers Med Sci 28(3):743–753

    Article  PubMed  Google Scholar 

  31. 31.

    Schiemann U, Avenhaus W, Konturek JW, Gellner R, Hengst K, Gross M (2003) Relationship of clinical features and laboratory parameters to thyroid echogenicity measured by standardized grey scale ultrasonography in patients with Hashimoto’s thyroiditis. Med Sci Monit 9((4)):MT13–MT17

    PubMed  Google Scholar 

  32. 32.

    Hofling DB, Chavantes MC, Juliano AG, Cerri GG, Knobel M, Yoshimura EM, Chammas MC (2012) Assessment of the effects of low-level laser therapy on the thyroid vascularization of patients with autoimmune hypothyroidism by color Doppler ultrasound. ISRN Endocrinol 2012:126720

    PubMed Central  PubMed  Google Scholar 

  33. 33.

    Duntas LH (2010) Selenium and the thyroid: a close-knit connection. J Clin Endocrinol Metab 95(12):5180–5188

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Schomburg L (2011) Selenium, selenoproteins and the thyroid gland: interactions in health and disease. Nat Rev Endocrinol 8(3):160–171

    Article  PubMed  Google Scholar 

  35. 35.

    McLachlan SM, Rapoport B (2014) Breaking tolerance to thyroid antigens: changing concepts in thyroid autoimmunity. Endocr Rev 35(1):59–105

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  36. 36.

    Xue H, Wang W, Li Y, Shan Z, Teng X, Gao Y, Fan C, Teng W (2010) Selenium upregulates CD4(+)CD25(+) regulatory T cells in iodine-induced autoimmune thyroiditis model of NOD.H-2(h4) mice. Endocr J 57(7):595–601

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Karunasinghe N, Han DY, Zhu S, Yu J, Lange K, Duan H, Medhora R, Singh N, Kan J, Alzaher W, Chen B, Ko S, Triggs CM, Ferguson LR (2012) Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins: relationship to markers of oxidative stress in men from Auckland, New Zealand. Genes Nutr 7(2):179–190

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  38. 38.

    Schulz SL, Seeberger U, Hengstmann JH (2003) Color Doppler sonography in hypothyroidism. Eur J Ultrasound 16(3):183–189

    Article  PubMed  Google Scholar 

  39. 39.

    Corona G, Biagini C, Rotondi M, Bonamano A, Cremonini N, Petrone L, Conforti B, Forti G, Serio M (2008) Correlation between, clinical, biochemical, color Doppler ultrasound thyroid parameters, and CXCL-10 in autoimmune thyroid diseases. Endocr J 55(2):345–350

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Chanoine JP, Neve J, Wu S, Vanderpas J, Bourdoux P (2001) Selenium decreases thyroglobulin concentrations but does not affect the increased thyroxine-to-triiodothyronine ratio in children with congenital hypothyroidism. J Clin Endocrinol Metab 86(3):1160–1163

    CAS  PubMed  Google Scholar 

  41. 41.

    Zimmermann MB, Andersson M (2012) Assessment of iodine nutrition in populations: past, present, and future. Nutr Rev 70(10):553–570

    Article  PubMed  Google Scholar 

  42. 42.

    Derumeaux H, Valeix P, Castetbon K, Bensimon M, Boutron-Ruault MC, Arnaud J, Hercberg S (2003) Association of selenium with thyroid volume and echostructure in 35- to 60-year-old French adults. Eur J Endocrinol 148(3):309–315

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Rasmussen LB, Schomburg L, Kohrle J, Pedersen IB, Hollenbach B, Hog A, Ovesen L, Perrild H, Laurberg P (2011) Selenium status, thyroid volume, and multiple nodule formation in an area with mild iodine deficiency. Eur J Endocrinol 164(4):585–590

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Brauer VF, Schweizer U, Kohrle J, Paschke R (2006) Selenium and goiter prevalence in borderline iodine sufficiency. Eur J Endocrinol 155(6):807–812

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Poppe K, Velkeniers B, Glinoer D (2008) The role of thyroid autoimmunity in fertility and pregnancy. Nat Clin Pract Endocrinol Metab 4(7):394–405

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    van Zuuren EJ, Albusta AY, Fedorowicz Z, Carter B, Pijl H (2014) Selenium supplementation for Hashimoto’s thyroiditis: summary of a Cochrane systematic review. Eur Thyroid J 3(1):25–31

    PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Berenice B. Mendonça (head of the Endocrinology Division), Marcos Maeda (statistics analyses), Milena Braga-Basaria (manuscript comments and editorial suggestions) and Jessica Kantrowitz (text editing) for their assistance. The study was supported by a grant from the “Fundação de Amparo à Pesquisa do Estado de São Paulo” (FAPESP) (No.: 2011/52059-3).

Conflict of interest

The authors have no potential conflict of interest to declare.

Ethical approval

All procedures performed in human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Author information

Affiliations

Authors

Corresponding author

Correspondence to M. Knobel.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

de Farias, C.R., Cardoso, B.R., de Oliveira, G.M.B. et al. 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 Invest 38, 1065–1074 (2015). https://doi.org/10.1007/s40618-015-0285-8

Download citation

Keywords

  • Thyroid gland
  • Selenium
  • Autoimmunity
  • Glutathione peroxidase GPx1
  • Polymorphism
  • Genetic