A pilot study on the beneficial effects of additional selenium supplementation to methimazole for treating patients with Graves’ disease
A pilot study on the beneficial effects of additional selenium supplementation to methimazole for treating patients with Graves’ disease
Background/aim: The aim of this study was to assess the effect of a combination use of methimazole (MMI) and selenium (Se) in thetreatment of Graves’ disease (GD).Materials and methods: A total of 103 newly diagnosed hyperthyroidism patients were randomized to MMI and MMI + Se combinationgroups. After treatment for 6 months, the levels of triiodothyronine (FT3), free thyroxine (FT4), thyrotropin receptor antibody (TRAb),thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were observed. An in vitro culture model of thyroid cellswas established and the protein expression and mRNA levels of TRAb, TPOAb, and TGAb were determined by western blot and RTPCR.Results: A significant decrease in the levels of FT3, FT4, TRAb, TPOAb, and TGAb were observed in both groups along with a markedincrease in TSH levels. Furthermore, the in vitro experiments showed that the protein expression and mRNA levels of TRAb, TPOAb,and TGAb decreased significantly. Also, compared to the MMI group, there was a greater improvement of these indices in the MMI +Se group.Conclusion: We suggest that the combined use of MMI and Se could improve the thyroid activity in patients, which may provide aneffective therapy for the treatment of GD in clinical settings.
___
- 1. Kahaly GJ, Grebe SK, Lupo MA, McDonald N, Sipos JA. Graves’
disease: diagnostic and therapeutic challenges (multimedia
activity). Am J Med 2011; 124: S2-3.
- 2. Bahn RS. Autoimmunity and Graves’ disease. Clin Pharmacol
Ther 2012; 91: 577-579.
- 3. Gunatilake SSC, Bulugahapitiya U. Coexistence of primary
hyperaldosteronism and Graves’ disease, a rare combination of
endocrine disorders: is it beyond a coincidence-a case report
and review of the literature. Case Rep Endocrinol 2017; 2017:
4050458.
- 4. Vanderpump MP. The epidemiology of thyroid disease. Br Med
Bull 2011; 99: 39-51.
- 5. Watt T, Cramon P, Bjorner JB, Bonnema SJ, Feldt-Rasmussen
U, Gluud CGJ, Hansen JL, Hegedüs L, Knudsen N, BachMortensen P et al. Selenium supplementation for patients with
Graves’ hyperthyroidism (the GRASS trial): study protocol for
a randomized controlled trial. Trials 2013; 14: 119.
- 6. Hegedus L. Treatment of Graves’ hyperthyroidism: evidencebased and emerging modalities. Endocrin Metab Clin 2009; 38:
355-371.
- 7. Glatstein MM, Garcia-Bournissen F, Giglio N, Finkelstein Y,
Koren G. Pharmacologic treatment of hyperthyroidism during
lactation. Can Fam Physician 2009; 55: 797-798.
- 8. Regelmann MO, Miloh T, Arnon R, Morotti R, Kerkar N,
Rapaport R. Graves’ disease presenting with severe cholestasis.
Thyroid 2012; 22: 437-439.
- 9. Yang M, Qu H, Deng HC. Acute pancreatitis induced by
methimazole in a patient with Graves’ disease. Thyroid 2012;
22: 94-96.
- 10. Tatara MR, Gołyński M, Radzki RP, Bieńko M, Krupski W.
Effects of long-term oral administration of methimazole
on femur and tibia properties in male Wistar rats. Biomed
Pharmacother 2017; 94: 124-128.
- 11. Trepanier LA. Pharmacologic management of feline
hyperthyroidism. Vet Clin North Am Small Anim Pract 2007;
37: 775-788.
- 12. Yang H, Cong Y, Wu T, Tang H, Ma M, Zeng J, Zhang WY, Lian
Z, Yang XY. Clinical efficacy of Yingliu mixture combined with
metimazole for treating diffuse goitre with hyperthyroidism and
its impact on related cytokines. Pharm Biol 2016; 55: 258-263.
- 13. Struja T, Kutz A, Fischli S, Meier C, Mueller B, Recher M,
Schuetz P. Is Graves’ disease a primary immunodeficiency? New
immunological perspectives on an endocrine disease. BMC Med
2017; 15: 174.
- 14. Wu X, Liu H, Zhu X, Shen J, Shi Y, Liu Z, Gu M, Song Z.
Efficacy and safety of methimazole ointment for patients with
hyperthyroidism. Environ Toxicol Pharmacol 2013; 36: 1109-
1112.
- 15. Seigel SC, Hodak SP. Thyrotoxicosis. Med Clin North Am 2012;
96: 175-201.
- 16. Dehina N, Hofmann PJ, Behrends T, Eckstein A, Schomburg L.
Lack of association between selenium status and disease severity
and activity in patients with Graves’ ophthalmopathy. European
Thyroid Journal 2016; 5: 57-64.
- 17. Al-Shammeri I, Al-Deen Mahmood S, Al-Mohannadi S,
Ballani N. Clinical experience of 2-hour I-131 thyroid uptake
significance in considering the radioiodine Graves’ disease
treatment dose: a retrospective study. Radiography 2015; 21:
254-257.
- 18. Holt K. Graves’ disease: clinical pathophysiology, presentation
and treatment options. J Pract Nurs 2010; 60: 13-18.
- 19. Stuss M, Michalska-Kasiczak M, Sewerynek E. The role of
selenium in thyroid gland pathophysiology. Endokrynol Pol
2017; 68: 440-465.
- 20. Hoffmann PR, Berry MJ. The influence of selenium on
immune responses. Mol Nutr Food Res 2008; 52: 1273-1280.
- 21. Rayman MP. The importance of selenium to human health.
Lancet 2000; 356: 233-241.
- 22. Dharmasena A. Selenium supplementation in thyroid
associated ophthalmopathy: an update. Int J Ophthalmol
2014; 7: 365-375.
- 23. Avery JC, Hoffmann PR. Selenium, selenoproteins, and
immunity. Nutrients 2018; 10: 1203.
- 24. Chaker L, Baumgartner C, den Elzen WP, Ikram MA,
Blum MR, Collet TH, Bakker SJ, Dehghan A, Drechsler C,
Luben RN et al. Subclinical hypothyroidism and the risk of
stroke events and fatal stroke: an individual participant data
analysis. J Clin Endocrinol Metab 2015; 1000: 2181-2191.
- 25. Nordio M, Pajalich R. Combined treatment with myoinositol and selenium ensures euthyroidism in subclinical
hypothyroidism patients with autoimmune thyroiditis.
Thyroid Res 2013; 2013: 424163.
- 26. Gartner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm
MW. Selenium supplementation in patients with
autoimmune thyroiditis decreases thyroid peroxidase
antibodies concentrations. J Clin Endocrinol Metab 2002;
87: 1687-1691.
- 27. Nordio M, Basciani S. Treatment with myo-inositol and
selenium ensures euthyroidism in patients with autoimmune
thyroiditis. Int J Endocrinol 2017; 2017: 2549491.
- 28. Nordio M, Basciani S. Myo-inositol plus selenium
supplementation restores euthyroid state in Hashimoto’s
patients with subclinical hypothyroidism. Eur Rev Med
Pharmacol Sci 2017; 21: 51-59.
- 29. Ferrari SM, Fallahi P, Di Bari F, Vita R, Benvenga S, Antonelli
A. Myo-inositol and selenium reduce the risk of developing
overt hypothyroidism in patients with autoimmune thyroiditis.
Eur Rev Med Pharmacol Sci 2017; 21: 36-42.
- 30. Vrca VB, Skreb F, Cepelak I, Romic Z, Mayer L. Supplementation
with antioxidants in the treatment of Graves’ disease; the
effect on glutathione peroxidase activity and concentration of
selenium. Clin Chim Acta 2004; 341: 55-63.
- 31. Wallaschofski H, Miehle K, Mayer A, Tuschy U, Hentschel
B, Paschke R. Prediction of remission or relapse for Graves’
hyperthyroidism by the combined determination of
stimulating, blocking and binding TSH-receptor antibodies
after the withdrawal of antithyroid drug treatment. Horm
Metab Res 2002; 34: 383-388.
- 32. Colobran R, Armengol Mdel P, Faner R, Gartner M, Tykocinski
LO, Lucas A, Ruiz M, Juan M, Kyewski B, Pujol-Borrell R.
Association of an SNP with intrathymic transcription of TSHR
and Graves’ disease: a role for defective thymic tolerance. Mol
Genet 2011; 20: 3415-3423.
- 33. Latrofa F, Ricci D, Montanelli L, Piaggi P, Mazzi B, Bianchi
F, Brozzi F, Santini P, Fiore E, Marino M et al. Thyroglobulin
autoantibodies switch to immunoglobulin (Ig)G1 and IgG3
subclasses and preserve their restricted epitope pattern after
131I treatment for Graves’ hyperthyroidism: the activity of
autoimmune disease influences subclass distribution but not
epitope pattern of autoantibodies. Clin Exp Immunol 2014;
178: 438-446.
- 34. Mazokopakis EE, Papadakis JA, Papadomanolaki MG,
Batistakis AG, Giannakopoulos TG, Protopapadakis
EE, Ganotakis ES. Effects of 12 months treatment with
L-selenomethionine on serum anti-TPO Levels in patients
with Hashimoto’s thyroiditis. Thyroid 2007; 17: 609-612.
- 35. Nacamulli D, Mian C, Petricca D, Lazzarotto F, Barollo S, Pozza
D, Masiero S, Faggian D, Plebani M, Girelli ME et al. Influence
of physiological dietary selenium supplementation on the
natural course of autoimmune thyroiditis. Clin Endocrinol
(Oxf) 2010; 73: 535-539.