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Selenium in the treatment of mild-to-moderate Graves’ orbitopathy: a 5-year prospective controlled cohort study

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Abstract

Purpose

Graves’ orbitopathy (GO) is the main extrathyroidal manifestation of Graves’ disease. However, limited studies have investigated the actual efficacy of selenium in GO therapy. This longitudinal study explored the effect of selenium on QOL and prognosis of patients with mild-to-moderate GO.

Methods

We conducted a 5-year prospective controlled cohort clinical trial to determine the effect of selenium on 74 patients with mild-to-moderate GO. Patients received selenium yeast or placebo orally for 6 months and were followed up at 6 months and at 5 years by biochemical examination, ophthalmologist evaluation and QOL questionnaire to assess oculopathy and QOL.

Results

(1) During a follow-up period of 3–6 months, in the selenium group, the symptoms of tearing, grittiness and conjunctival congestion improved (P < 0.01); clinical activity scores and total GO-QOL scores increased relative to baseline (P < 0.01); TRAb was decreased at the 6-month evaluation (P = 0.003); and patients treated with selenium had a higher rate of improvement and a lower rate of worsening than patients treated with placebo (P < 0.05). (2) Exploratory evaluations at 6 months after drug withdrawal confirmed the earlier results; further changes included alleviation of blurred vision and double vision symptoms in the selenium group (P < 0.01). (3) At the 5-year follow-up, compared with baseline, proptosis, clinical activity scores, TRAb level and total GO-QOL scores in both the selenium and placebo groups were significantly improved (P < 0.01).

Conclusion

Six months of selenium supplementation may effectively change the early course of mild-to-moderate GO, but this regimen makes no difference in long-term outcomes.

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Data availability

All datasets generated during and analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

References

  1. L. Bartalena, G.J. Kahaly, L. Baldeschi, C.M. Dayan, A. Eckstein, C. Marcocci, M. Marinò, B. Vaidya, W.M. Wiersinga, The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur. J. Endocrinol. 185, G43–g67 (2021)

    Article  CAS  PubMed  Google Scholar 

  2. L. Bartalena, E. Piantanida, D. Gallo, A. Lai, M.L. Tanda, Epidemiology, natural history, risk factors, and prevention of Graves’ orbitopathy. Front. Endocrinol. 11, 615993 (2020)

    Article  Google Scholar 

  3. L. Bartalena, L. Baldeschi, K. Boboridis, A. Eckstein, G.J. Kahaly, C. Marcocci, P. Perros, M. Salvi, W.M. Wiersinga, The 2016 European Thyroid Association/European Group on Graves’ Orbitopathy Guidelines for the Management of Graves’ Orbitopathy. Eur. Thyroid J. 5, 9–26 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. L. Bartalena, L. Baldeschi, A. Dickinson, A. Eckstein, P. Kendall-Taylor, C. Marcocci, M. Mourits, P. Perros, K. Boboridis, A. Boschi, N. Currò, C. Daumerie, G.J. Kahaly, G.E. Krassas, C.M. Lane, J.H. Lazarus, M. Marinò, M. Nardi, C. Neoh, J. Orgiazzi, S. Pearce, A. Pinchera, S. Pitz, M. Salvi, P. Sivelli, M. Stahl, G. von Arx, W.M. Wiersinga, Consensus statement of the European Group on Graves’ orbitopathy (EUGOGO) on management of GO. Eur. J. Endocrinol. 158, 273–285 (2008)

    Article  CAS  PubMed  Google Scholar 

  5. R.S. Bahn, Graves’ ophthalmopathy. N. Engl. J. Med. 362, 726–738 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. W.M. Wiersinga, Quality of life in Graves’ ophthalmopathy. Best. Pract. Res. Clin. Endocrinol. Metab. 26, 359–370 (2012)

    Article  PubMed  Google Scholar 

  7. K.A. Ponto, S. Merkesdal, G. Hommel, S. Pitz, N. Pfeiffer, G.J. Kahaly, Public health relevance of Graves’ orbitopathy. J. Clin. Endocrinol. Metab. 98, 145–152 (2013)

    Article  CAS  PubMed  Google Scholar 

  8. C.B. Terwee, F.W. Dekker, M.P. Mourits, M.N. Gerding, L. Baldeschi, R. Kalmann, M.F. Prummel, W.M. Wiersinga, Interpretation and validity of changes in scores on the Graves’ ophthalmopathy quality of life questionnaire (GO-QOL) after different treatments. Clin. Endocrinol. 54(3), 391–398 (2001)

    Article  CAS  Google Scholar 

  9. L. Bartalena, W.M. Wiersinga, Proposal for standardization of primary and secondary outcomes in patients with active, moderate-to-severe Graves’ orbitopathy. Eur. thyroid J. 9, 3–16 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. W. Wiersinga, M. Žarković, L. Bartalena, S. Donati, P. Perros, O. Okosieme, D. Morris, N. Fichter, J. Lareida, G. von Arx, C. Daumerie, M.C. Burlacu, G. Kahaly, S. Pitz, B. Beleslin, J. Ćirić, G. Ayvaz, O. Konuk, F.B. Törüner, M. Salvi, D. Covelli, N. Curro, L. Hegedüs, T. Brix, Predictive score for the development or progression of Graves’ orbitopathy in patients with newly diagnosed Graves’ hyperthyroidism. Eur. J. Endocrinol. 178, 635–643 (2018)

    Article  CAS  PubMed  Google Scholar 

  11. R. Negro, L. Hegedüs, R. Attanasio, E. Papini, K.H. Winther, A 2018 European Thyroid Association Survey on the Use of Selenium Supplementation in Graves’ Hyperthyroidism and Graves’ Orbitopathy. Eur. thyroid J. 8, 7–15 (2019)

    Article  PubMed  Google Scholar 

  12. M. Ventura, M. Melo, F. Carrilho, Selenium and thyroid disease: From pathophysiology to treatment. Int. J. Endocrinol. 2017, 1297658 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  13. G. Lanzolla, M. Marinò, C. Marcocci, Selenium in the treatment of Graves’ hyperthyroidism and eye disease. Front. Endocrinol. 11, 608428 (2021)

    Article  Google Scholar 

  14. M. Weissel, Selenium and the course of mild Graves’ orbitopathy. N. Engl. J. Med. 365, 769–770 (2011). author reply 770-761

    Article  CAS  PubMed  Google Scholar 

  15. E. Hoppe, A.C.H. Lee, D. Hoppe, G.J. Kahaly, Predictive factors for changes in quality of life after steroid treatment for active moderate-to-severe Graves’ orbitopathy: a prospective trial. Eur. Thyroid J. 9, 313–320 (2021)

    Article  PubMed  Google Scholar 

  16. M. Lumyongsatien, B. Keeratidamkerngsakul, K. Pornpanich, S. Vangveeravong, P. Saonanon, D. Wiwatwongwana, P. Mahaisavariya, O. Aryasit, K. Pongpirul, Development and psychometric properties of the Thai Graves’ ophthalmopathy quality of life (GO-QOL) questionnaire. J. Patient-Rep. Outcomes 4(1), 1 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  17. D. Villagelin, J. Romaldini, J. Andrade, R. Santos, A. Milkos, P. Teixeira, L.S. Ward, Evaluation of quality of life in the Brazilian Graves’ disease population: focus on mild and moderate Graves’ orbitopathy patients. Front. Endocrinol. 10, 192 (2019)

    Article  Google Scholar 

  18. C.M. Riguetto, A.M. Neto, M.A. Tambascia, D.E. Zantut-Wittmann, The relationship between quality of life, cognition, and thyroid status in Graves’ disease. Endocrine 63, 87–93 (2019)

    Article  CAS  PubMed  Google Scholar 

  19. Y. Liu, S. Liu, J. Mao, S. Piao, J. Qin, S. Peng, X. Xie, H. Guan, Y. Li, Z. Shan, W. Teng, Serum trace elements profile in Graves’ disease patients with or without orbitopathy in Northeast China. BioMed. Res. Int. 2018, 3029379 (2018)

    PubMed  PubMed Central  Google Scholar 

  20. G.J. Kahaly, Management of graves thyroidal and extrathyroidal disease: an update. J. Clin. Endocrinol. Metab. 105, 3704–3720 (2020)

    Article  PubMed  PubMed Central  Google Scholar 

  21. L. Bartalena, M.L. Tanda, E. Piantanida, A. Lai, Oxidative stress and Graves’ ophthalmopathy: in vitro studies and therapeutic implications. BioFactors (Oxf., Engl.) 19, 155–163 (2003)

    Article  CAS  Google Scholar 

  22. T. Diana, K.A. Ponto, G.J. Kahaly, Thyrotropin receptor antibodies and Graves’ orbitopathy. J. Endocrinol. Investig. 44, 703–712 (2021)

    Article  CAS  Google Scholar 

  23. A. George, T. Diana, J. Längericht, G.J. Kahaly, Stimulatory thyrotropin receptor antibodies are a biomarker for Graves’ orbitopathy. Front. Endocrinol. Feb 2 11, 629925 (2021)

    Article  Google Scholar 

  24. D. Łacheta, P. Miśkiewicz, A. Głuszko, G. Nowicka, M. Struga, I. Kantor, K.B. Poślednik, S. Mirza, M.J. Szczepański, Immunological aspects of Graves’ ophthalmopathy. BioMed. Res. Int. 2019, 7453260 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  25. J.C. Avery, P.R. Hoffmann, Selenium, selenoproteins, and immunity. Nutrients 10, 1203 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  26. M. Almanza-Monterrubio, L. Garnica-Hayashi, A. Dávila-Camargo, Á. Nava-Castañeda, Oral selenium improved the disease activity in patients with mild Graves’ orbitopathy. J. francais d’ophtalmologie 44, 643–651 (2021)

    Article  CAS  Google Scholar 

  27. F. Nicolì, G. Lanzolla, M. Mantuano, I. Ionni, B. Mazzi, M. Leo, A. Sframeli, C. Posarelli, M.N. Maglionico, M. Figus, M. Nardi, C. Marcocci, M. Marinò, Correlation between serum anti-TSH receptor autoantibodies (TRAbs) and the clinical feature of Graves’ orbitopathy. J. Endocrinol Investig. 44, 581–585 (2021)

    Article  Google Scholar 

  28. Y.J. Choi, H.T. Lim, S.J. Lee, S.Y. Lee, J.S. Yoon, Assessing Graves’ ophthalmopathy-specific quality of life in Korean patients. Eye (Lond., Engl.) 26, 544–551 (2012)

    Article  CAS  Google Scholar 

  29. I.C. Lin, C.C. Lee, S.L. Liao, Assessing quality of life in Taiwanese patients with Graves’ ophthalmopathy. J. Formos. Med. Assoc. 114(11), 1047–1054 (2015)

    Article  PubMed  Google Scholar 

  30. C.Y. Weng, Z.F. Li, S.D. Hu, Y.S. Luo, X.T. Feng, Q. Zhong, Q. Zhang, J. Shen, Evaluation of quality of life in patients with Graves orbitopathy and its influencing factors. Zhonghua nei ke za zhi 58, 577–583 (2019)

    CAS  PubMed  Google Scholar 

  31. L.C. Delfino, A. Zunino, V. Sapia, M. Croome, V. Ilera, A.T. Gauna, Related quality of life questionnaire specific to dysthyroid ophthalmopathy evaluated in a population of patients with Graves’ disease. Arch. Endocrinol. Metab. 61, 374–381 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  32. F. Menconi, M.A. Profilo, M. Leo, E. Sisti, M.A. Altea, R. Rocchi, F. Latrofa, M. Nardi, P. Vitti, C. Marcocci, M. Marinò, Spontaneous improvement of untreated mild Graves’ ophthalmopathy: Rundle’s curve revisited. Thyroid Jan. 24(1), 60–66 (2014)

    Article  CAS  Google Scholar 

  33. P. Anagnostis, K. Boboridis, F. Adamidou, M. Kita, Natural course of mild Graves’ orbitopathy: is it a chronic remitting or a transient disease? J. Endocrinol. Investig. 40, 257–261 (2017)

    Article  CAS  Google Scholar 

  34. G.B. Bartley, V. Fatourechi, E.F. Kadrmas, S.J. Jacobsen, D.M. Ilstrup, J.A. Garrity, C.A. Gorman, Long-term follow-up of Graves ophthalmopathy in an incidence cohort. Ophthalmology 103, 958–962 (1996)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank all the participants of this study.

Funding

This work was supported by the National Natural Science Foundation of China (81570709, 82270833, 82300886). the Science Research Fund Project of Education Department of Liaoning Province (General Project) (LJKZ0742), and the Science Research Fund Project of Shenyang Science and Technology Bureau [2011] (21, F11-262-9-23).

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Authors and Affiliations

  1. The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Shenyang, P.R. China

    Chuyuan Wang, Jing Qiao, Sichen Piao, Ruolin Hu, Haoyu Wang, Weiwei Wang, Lei Zhao, Jinyuan Mao, Weiping Teng, Zhongyan Shan & Yushu Li

  2. Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, 110001, P.R. China

    Chuyuan Wang, Haoyu Wang, Weiwei Wang, Min Li, Weiping Teng, Zhongyan Shan & Yushu Li

  3. Department of Second Medicine, Liaoning Provincial Corps Hospital of Chinese People’s Armed Police Force, Shenyang, P.R. China

    Shanshan Liu

  4. Department of Ophthalmology, The First Hospital of China Medical University, Shenyang, 110001, P.R. China

    Yun Zhou, Yuedong Hu, Chao Wan, Yizhou Sun, Hong Ning & Lei Chen

  5. Department of Nutrition, The Fourth People’s Hospital of China Medical University, Shenyang, Liaoning, China

    He Zhang

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  1. Chuyuan Wang
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Contributions

Y.S.L. and Z.Y.S. conceived of and designed the study; C.Y.W., J.Q., S.S.L. and S.P. organized the study and conducted the statistical analysis. Second authors J.Q., S.S.L., and S.P. contributed equally. All authors contributed to the acquisition, analysis, or interpretation of data. Y.S.L., Z.Y.S. and C.Y.W. drafted the manuscript. All authors revised the report and approved the final version before submission.

Corresponding authors

Correspondence to Zhongyan Shan or Yushu Li.

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Conflict of interest

The authors declare no competing interests.

Ethical approval

This study was approved by the Ethics Committee of China Medical University and registered in the China Clinical Trial Registry (Registration Number: CHICTR-IOR-15005855). All the participants signed informed consent forms before enrollment. The study will be implemented and reported in line with the STROBE statement.

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

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Wang, C., Qiao, J., Liu, S. et al. Selenium in the treatment of mild-to-moderate Graves’ orbitopathy: a 5-year prospective controlled cohort study. Endocrine (2024). https://doi.org/10.1007/s12020-023-03672-5

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