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open access

Vol 71, No 5 (2020)
Original paper
Submitted: 2020-05-02
Accepted: 2020-07-01
Published online: 2020-08-03
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The effect of thyroid hormone status on selected antioxidant parameters in patients with Graves’ disease and active thyroid-associated orbitopathy

Magdalena Londzin-Olesik1, Beata Kos-Kudła1, Aleksandra Nowak2, Tomasz Wielkoszyński3, Mariusz Nowak4
DOI: 10.5603/EP.a2020.0049
·
Pubmed: 32797475
·
Endokrynol Pol 2020;71(5):418-424.
Affiliations
  1. Department of Endocrinology and Neuroendocrine Tumours, Department of Pathophysiology and Endocrinology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
  2. Science Students’ Association, Department of Pathophysiology and Endocrinology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
  3. Higher School of Strategic Planning, Dąbrowa Górnicza, Poland
  4. Division of Pathophysiology, Department of Pathophysiology and Endocrinology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland

open access

Vol 71, No 5 (2020)
Original Paper
Submitted: 2020-05-02
Accepted: 2020-07-01
Published online: 2020-08-03

Abstract

Introduction: Oxidative stress has been implicated in the pathogenesis of thyroid-associated orbitopathy (TAO) in patients with Graves’ disease (GD). This study assessed the effect of thyroid hormone abnormalities on selected antioxidant parameters in patients with active TAO.

Material and methods: The study group consisted of 56 patients with GD and active TAO treated with antithyroid medication. Depending on the thyroid hormone level, they were subdivided into two groups: Group 1 — hyperthyroid patients (n = 34) and Group 2 — euthyroid patients (n = 22). The total oxidant status expressed as the ferric reducing ability of plasma (FRAP) as well as selected enzymatic and nonenzymatic components of the antioxidant system, including the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and paraoxonase 1 (PON-1), as well as the levels of vitamin C, uric acid, and lipid peroxidation products: malondialdehyde (MDA) and conjugated dienes (CD) were assessed in all enrolled participants.

Results: The FRAP values in Group 1 were significantly higher than in controls. The FRAP values in Group 2 were lower than in Group 1 and higher than in controls. However, the differences were not significant. In Group 1, the activity of SOD and GPx, as well as serum levels of uric acid, MDA, and CD, were significantly higher than in controls. At the same time, serum PON-1 activity and vitamin C levels were significantly lower in Group 1 than in controls. In Group 2, the SOD activity as well as MDA and CD levels were non-significantly lower than in Group 1 and non-significantly higher than in controls. The activity of GPx in euthyroid patients with TAO was significantly higher than in controls.

Conclusions: Hyperthyroidism is a significant contributor to oxidative stress in patients with active TAO, which manifests as upregulated lipid peroxidation and antioxidant system activation. Euthyroid state restoration leads to a relative reduction in activity and levels of most studied antioxidant parameters, which still remain above the normal values. The autoimmune inflammation of the orbital tissue seems to be a thyroid hormone status-independent modifier of oxidative stress. 

Abstract

Introduction: Oxidative stress has been implicated in the pathogenesis of thyroid-associated orbitopathy (TAO) in patients with Graves’ disease (GD). This study assessed the effect of thyroid hormone abnormalities on selected antioxidant parameters in patients with active TAO.

Material and methods: The study group consisted of 56 patients with GD and active TAO treated with antithyroid medication. Depending on the thyroid hormone level, they were subdivided into two groups: Group 1 — hyperthyroid patients (n = 34) and Group 2 — euthyroid patients (n = 22). The total oxidant status expressed as the ferric reducing ability of plasma (FRAP) as well as selected enzymatic and nonenzymatic components of the antioxidant system, including the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and paraoxonase 1 (PON-1), as well as the levels of vitamin C, uric acid, and lipid peroxidation products: malondialdehyde (MDA) and conjugated dienes (CD) were assessed in all enrolled participants.

Results: The FRAP values in Group 1 were significantly higher than in controls. The FRAP values in Group 2 were lower than in Group 1 and higher than in controls. However, the differences were not significant. In Group 1, the activity of SOD and GPx, as well as serum levels of uric acid, MDA, and CD, were significantly higher than in controls. At the same time, serum PON-1 activity and vitamin C levels were significantly lower in Group 1 than in controls. In Group 2, the SOD activity as well as MDA and CD levels were non-significantly lower than in Group 1 and non-significantly higher than in controls. The activity of GPx in euthyroid patients with TAO was significantly higher than in controls.

Conclusions: Hyperthyroidism is a significant contributor to oxidative stress in patients with active TAO, which manifests as upregulated lipid peroxidation and antioxidant system activation. Euthyroid state restoration leads to a relative reduction in activity and levels of most studied antioxidant parameters, which still remain above the normal values. The autoimmune inflammation of the orbital tissue seems to be a thyroid hormone status-independent modifier of oxidative stress. 

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Keywords

antioxidant parameters; hyperthyroidism; Graves’ disease; lipid peroxidation; thyroid orbitopathy

About this article
Title

The effect of thyroid hormone status on selected antioxidant parameters in patients with Graves’ disease and active thyroid-associated orbitopathy

Journal

Endokrynologia Polska

Issue

Vol 71, No 5 (2020)

Article type

Original paper

Pages

418-424

Published online

2020-08-03

Page views

1314

Article views/downloads

849

DOI

10.5603/EP.a2020.0049

Pubmed

32797475

Bibliographic record

Endokrynol Pol 2020;71(5):418-424.

Keywords

antioxidant parameters
hyperthyroidism
Graves’ disease
lipid peroxidation
thyroid orbitopathy

Authors

Magdalena Londzin-Olesik
Beata Kos-Kudła
Aleksandra Nowak
Tomasz Wielkoszyński
Mariusz Nowak

References (53)
  1. Laurberg P, Pedersen KM, Vestergaard H, et al. High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves' disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland. J Intern Med. 1991; 229(5): 415–420.
    CrossRefPubMed
  2. Wall JR, Lahooti H, Wall JR, et al. Pathogenesis of thyroid eye disease--does autoimmunity against the TSH receptor explain all cases? Endokrynol Pol. 2010; 61(2): 222–227.
    PubMed
  3. Effraimidis G, Wiersinga WM. Mechanisms in endocrinology: autoimmune thyroid disease: old and new players. Eur J Endocrinol. 2014; 170(6): R241–R252.
    CrossRefPubMed
  4. Dong YH, Fu DG. Autoimmune thyroid disease: mechanism, genetics and current knowledge. Eur Rev Med Pharmacol Sci. 2014; 18(23): 3611–3618.
    PubMed
  5. Poncin S, Colin IM, Decallonne B, et al. N-acetylcysteine and 15 deoxy-{delta}12,14-prostaglandin J2 exert a protective effect against autoimmune thyroid destruction in vivo but not against interleukin-1{alpha}/interferon {gamma}-induced inhibitory effects in thyrocytes in vitro. Am J Pathol. 2010; 177(1): 219–228.
    CrossRefPubMed
  6. Venditti P, Di Meo S. Thyroid hormone-induced oxidative stress. Cell Mol Life Sci. 2006; 63(4): 414–434.
    CrossRefPubMed
  7. Halliwell B, Gutteridge J. [1] Role of free radicals and catalytic metal ions in human disease: An overview. Methods Enzymol. 1990; 186: 1–85.
    CrossRefPubMed
  8. Abraham-Nordling M, Byström K, Törring O, et al. Incidence of hyperthyroidism in Sweden. Eur J Endocrinol. 2011; 165(6): 899–905.
    CrossRefPubMed
  9. Laurberg P, Berman DC, Bülow Pedersen I, et al. Incidence and clinical presentation of moderate to severe graves' orbitopathy in a Danish population before and after iodine fortification of salt. J Clin Endocrinol Metab. 2012; 97(7): 2325–2332.
    CrossRefPubMed
  10. Tanda ML, Piantanida E, Liparulo L, et al. Prevalence and natural history of Graves' orbitopathy in a large series of patients with newly diagnosed graves' hyperthyroidism seen at a single center. J Clin Endocrinol Metab. 2013; 98(4): 1443–1449.
    CrossRefPubMed
  11. Maheshwari R, Weis E. Thyroid associated orbitopathy. Indian J Ophthalmol. 2012; 60(2): 87–93.
    CrossRefPubMed
  12. Smith TJ, Hegedüs L, Douglas RS. Role of insulin-like growth factor-1 (IGF-1) pathway in the pathogenesis of Graves' orbitopathy. Best Pract Res Clin Endocrinol Metab. 2012; 26(3): 291–302.
    CrossRefPubMed
  13. Turck N, Eperon S, De Los Angeles Gracia M, et al. Thyroid-Associated Orbitopathy and Biomarkers: Where We Are and What We Can Hope for the Future. Dis Markers. 2018; 2018: 7010196.
    CrossRefPubMed
  14. Mizokami T, Salvi M, Wall JR. Eye muscle antibodies in Graves' ophthalmopathy: pathogenic or secondary epiphenomenon? J Endocrinol Invest. 2004; 27(3): 221–229.
    CrossRefPubMed
  15. Seethalakshmi I, Bahn R. Immunopathogenesis of Graves’ ophthalmopathy: the role of the TSH receptor. Best Pract Res Clin Endocrinol Metab. 2012; 26: 281-289, doi: 1; 26(3): 281–289.
    CrossRefPubMed
  16. Gianoukakis AG, Khadavi N, Smith TJ. Cytokines, Graves' disease, and thyroid-associated ophthalmopathy. Thyroid. 2008; 18(9): 953–958.
    CrossRefPubMed
  17. Mysliwiec J, Palyga I, Nikolajuk A, et al. Serum interleukin-16 and RANTES during treatment of Graves' orbitopathy with corticosteroids and teleradiotherapy. Endokrynol Pol. 2012; 63(2): 92–96.
    PubMed
  18. Nowak M, Siemińska L, Karpe J, et al. Serum concentrations of HGF and IL-8 in patients with active Graves' orbitopathy before and after methylprednisolone therapy. J Endocrinol Invest. 2016; 39(1): 63–72.
    CrossRefPubMed
  19. Nowak M, Marek B, Karpe J, et al. Serum concentration of VEGF and PDGF-AA in patients with active thyroid orbitopathy before and after immunosuppressive therapy. Exp Clin Endocrinol Diabetes. 2014; 122(10): 582–586.
    CrossRefPubMed
  20. Shuai M, Ni Y, Jian Xu, et al. The level of IL-35 in the circulation of patients with Graves' disease. Endokrynol Pol. 2019; 70(4): 318–322.
    CrossRefPubMed
  21. Bahn RS. Graves’ ophthalmopathy. N Engl J Med. 2010; 362(8): 726–738.
    CrossRefPubMed
  22. Bartalena L, Baldeschi L, Boboridis K, et al. European Group on Graves' Orbitopathy (EUGOGO). The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy. Eur Thyroid J. 2016; 5(1): 9–26.
    CrossRefPubMed
  23. Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay. Anal Biochem. 1996; 239(1): 70–76.
    CrossRefPubMed
  24. Ōyanagui Y. Reevaluation of assay methods and establishment of kit for superoxide dismutase activity. Anal Biochem. 1984; 142(2): 290–296.
    CrossRefPubMed
  25. Paglia D, Valentine W. Studies on the quantities and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin. 1967; 70(1): 158–169.
    PubMed
  26. Eckerson HW, Romson J, Wyte C, et al. The human serum paraoxonase polymorphism: indentification of phenotypes by their response to salts. Am J Hum Genet . 1983; 35(2): 214–227.
    PubMed
  27. Wielkoszyński T. Spectrophotometric method of determination L-ascorbic acid concentration in biological material. Diagn Lab. 2001; 37(2): 172.
  28. Wasowicz W, Nève J, Peretz A. Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage. Clin Chem. 1993; 39(12): 2522–2526.
    PubMed
  29. Corongiu FP, Banni S, Dessi MA. Conjugated dienes detected in tissue lipid extracts by second derivative spectrophotometry. Free Radical Biology and Medicine. 1989; 7(2): 183–186.
    CrossRef
  30. Hübner G, Meng W, Meisel P, et al. [Behavior of the erythrocyte glucose-6-phosphate dehydrogenase in patients with functional thyroid disorders and in hyperthyroxinemic rats]. Z Gesamte Inn Med. 1979; 34(14): 386–389.
    PubMed
  31. Akarsu E, Buyukhatipoglu H, Aktaran S, et al. Effects of pulse methylprednisolone and oral methylprednisolone treatments on serum levels of oxidative stress markers in Graves' ophthalmopathy. Clin Endocrinol (Oxf). 2011; 74(1): 118–124.
    CrossRefPubMed
  32. Choi W, Li Y, Ji Y, et al. Oxidative stress markers in tears of patients with Graves’ orbitopathy and their correlation with clinical activity score. BMC Ophthalmol. 2018; 18(1).
    CrossRefPubMed
  33. Bednarek J, Wysocki H, Sowiński J. Peripheral parameters of oxidative stress in patients with infiltrative Graves' ophthalmopathy treated with corticosteroids. Immunol Lett. 2004; 93(2-3): 227–232.
    CrossRefPubMed
  34. Bednarek J, Wysocki H, Sowiński J. Oxidative stress peripheral parameters in Graves' disease: the effect of methimazole treatment in patients with and without infiltrative ophthalmopathy. Clin Biochem. 2005; 38(1): 13–18.
    CrossRefPubMed
  35. Bednarek J, Wysocki H, Sowinski J. Oxidation products and antioxidant markers in plasma of patients with Graves' disease and toxic multinodular goiter: effect of methimazole treatment. Free Radic Res. 2004; 38(6): 659–664.
    CrossRefPubMed
  36. Rajkovic MG, Rumora L, Barisic K. The paraoxonase 1, 2 and 3 in humans. Biochem Med (Zagreb). 2011; 21(2): 122–130.
    CrossRefPubMed
  37. James RW. A long and winding road: defining the biological role and clinical importance of paraoxonases. Clin Chem Lab Med. 2006; 44(9): 1052–1059.
    CrossRefPubMed
  38. Ikeda Y, Suehiro T, Inoue M, et al. Serum paraoxonase activity and its relationship to diabetic complications in patients with non—insulin-dependent diabetes mellitus. Metabolism. 1998; 47(5): 598–602.
    CrossRefPubMed
  39. Tomás M, Latorre G, Sentí M, et al. [The antioxidant function of high density lipoproteins: a new paradigm in atherosclerosis]. Rev Esp Cardiol. 2004; 57(6): 557–569.
    PubMed
  40. Azizi F, Raiszadeh F, Solati M, et al. Serum paraoxonase 1 activity is decreased in thyroid dysfunction. J Endocrinol Invest. 2003; 26(8): 703–709.
    CrossRefPubMed
  41. Raiszadeh F, Solati M, Etemadi A, et al. Serum paraoxonase activity before and after treatment of thyrotoxicosis. Clin Endocrinol (Oxf). 2004; 60(1): 75–80.
    CrossRefPubMed
  42. Yavuz DG, Yüksel M, Deyneli O, et al. Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goitre patients. Clin Endocrinol (Oxf). 2004; 61(4): 515–521.
    CrossRefPubMed
  43. Baskol G, Dolbun Se, Bayram F, et al. Investigation of serum paraoxonase-1 activity and lipid levels in patients with hyperthyroidism. Turk J Med Sci. 2012; 42(1): 1166–1171.
    CrossRef
  44. Yuksel N, Yaman D, Tugce Pasaoglu O, et al. The Effect of Smoking on Mitochondrial Biogenesis in Patients With Graves Ophthalmopathy. Ophthalmic Plast Reconstr Surg. 2020; 36(2): 172–177.
    CrossRefPubMed
  45. Ames BN, Cathcart R, Schwiers E, et al. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci USA. 1981; 78(11): 6858–6862.
    CrossRefPubMed
  46. Ye Y, Gai X, Xie H, et al. Association between serum free thyroxine (FT4) and uric acid levels in populations without overt thyroid dysfunction. Science Ann Clin Lab Sci. 2015; 45(1): 49–53.
    PubMed
  47. Liu X, Zhang J, Meng Z, et al. Gender impact on the correlations between Graves' hyperthyroidism and hyperuricemia in Chinese. Ir J Med Sci. 2019; 188(3): 843–848.
    CrossRefPubMed
  48. Sato A, Shirota T, Shinoda T, et al. Hyperuricemia in patients with hyperthyroidism due to graves' disease. Metabolism. 1995; 44(2): 207–211.
    CrossRefPubMed
  49. Seven A, Taşan E, Inci F, et al. Biochemical evaluation of oxidative stress in propylthiouracil treated hyperthyroid patients. Effects of vitamin C supplementation. Clin Chem Lab Med. 1998; 36(10): 767–770.
    CrossRefPubMed
  50. Rotondo Dottore G, Ionni I, Menconi F, et al. Action of three bioavailable antioxidants in orbital fibroblasts from patients with Graves' orbitopathy (GO): a new frontier for GO treatment? J Endocrinol Invest. 2018; 41(2): 193–201.
    CrossRefPubMed
  51. Karasek D, Cibickova L, Karhanova M, et al. Clinical and immunological changes in patients with active moderate-to-severe Graves' orbitopathy treated with very low-dose rituximab. Endokrynol Pol. 2017; 68(5): 498–504.
    CrossRefPubMed
  52. Russell DJ, Wagner LH, Seiff SR. Tocilizumab as a steroid sparing agent for the treatment of Graves' orbitopathy. Am J Ophthalmol Case Rep. 2017; 7: 146–148.
    CrossRefPubMed
  53. Świerkot M, Kulawik G, Sarnat-Kucharczyk M, et al. Long-term remission of steroid-resistant Graves' orbitopathy after administration of anti-thymocyte globulin. Endokrynol Pol. 2020; 71(2): 198–199.
    CrossRefPubMed

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