J.ophthalmol.(Ukraine).2019;6:49-55.
http://doi.org/10.31288/oftalmolzh201964955
Received: 17 October 2019; Published on-line: 06 January 2020
Asssociation of vitamin D with autoimmune ophthalmopathy in Graves’ disease
Yu.V. Buldygina, Cand Sc (Med); G.M. Terekhova, Cand Sc (Med); L.S. Strafun, Junior Research Fellow; T.V. Fed’ko, Endocrinologist; V.M. Klochkova, Research Fellow; I.I. Savosko, Endocrinologist; Z.G. Lysova, Endocrinologist
Komisarenko Institute for Endocrinology and Metabolism of the NAMS of Ukraine; Kyiv (Ukraine)
E-mail: Yuliya.buldygina@icloud.com
TO CITE THIS ARTICLE: Buldygina YuV, Terekhova GM, Strafun LS, Fed’ko TV, Klochkova VM, Savosko II, Lysova ZG. Asssociation of vitamin D with autoimmune ophthalmopathy in Graves’ disease. J.ophthalmol.(Ukraine).2019;6:49-55. http://doi.org/10.31288/oftalmolzh201964955
Background: The role of vitamin D in the development of autoimmune thyroid diseases has been actively discussed in the recent literature. Numerous studies have demonstrated an association of low vitamin D levels with autoimmune thyroiditis, with correlations with antithyroid antibody levels, thyroid hormone levels, disease severity and thyroid gland volume, both in adults and in children. However, there are a few relevant reports on Graves’ disease (GD), and only one relevant report is available on GD associated with autoimmune ophthalmopathy (AO). Given that GD complicated by AO is a classic autoimmune disease, it will be interesting to investigate the role of vitamin D in its pathogenesis.
Purpose: To examine vitamin D levels and to determine correlations between this characteristic and thyroid-stimulating hormone receptor antibodies (TSH-R-Ab) in patients with Graves’ disease complicated by immune ophthalmopathy.
Material and Methods: Serum levels of 25(OH)D, TSH, TSH-R-Ab and parathyroidal hormone (PTH) were measured in 131 patients with GD. Study patients were divided into two groups based on the presence or absence of ophthalmopathy. Group 1 comprised 81 GD patients with AO, and group 2 comprised 50 GD patients without AO. Clinical severity of AO was classified using the NOSPECS. Thirty-two, 30 and 19 patients had class 2b, class 3a or 3b, and class 4a, respectively. Variation statistics with Student t test was used for statistical analyses. The level of significance p ? 0.05 was assumed. Data are presented as mean ± standard error of mean. Pearson correlation analysis was used to identify possible correlations between variables.
Results: All patients were euthyroid, and the mean TSH level in group 1 was 1.33±0.35 mU/L, and in group 2, 0.5 ± 0.2 mU/L (Р > 0.05). TSH-R-Ab levels were higher than normal in both groups of patients (group 1: range, 0.8 U/L to 21 U/L , mean value, 14.05± 2.7 U/L ; group 2: range, 1.8 U/L to 14.3 U/L , mean value, 31.0 ± 2.22 U/L; the difference between groups was not significant, р > 0.05). This was anticipated since these abnormalities are pathogenetic in GD. Serum levels of 25(OH)D in both groups were lower than normal (42.98 ± 2.82 nmol/L in group 1 vs 58.12 ± 4.2 nmol/L in group 2; р<0.02). Serum 25(OH)D concentrations were statistically significantly lower in Graves’ disease patients with AO, than in those without ophthalmopathy, and corresponded to vitamin D deficiency and suboptimal status, respectively. There was a significant difference in serum 25(OH)D level, but not in PTH level between the groups. Thus, mean serum PTH level in group 1 was 65.85±4.79 pg/mL, vs 49.73±11.4 pg/mL in group 2 (р > 0.05). TSH-R-Ab levels were negatively linearly correlated with the serum 25(OH)D level in the study cohort (elevated TSH-R-Ab levels correlated with low 25(OH)D levels).
Conclusion: First, there was no statistically significant difference in TSH-R-Ab levels between Graves’ disease patients with AO and those without AO (14.05±2.7 U/L and 31±2.22 U/L, respectively; р > 0.05). Second, the mean serum 25(OH)D level for the study cohort of Graves’ disease patients (47.63 ± 2.48 nmol/L) was insufficient, and the mean level for patients with AO was significantly lower than the mean level for patients without AO (42.98 ± 2.82 nmol/L vs 58.12 ± 4.2 nmol/L; р<0.02). Finally, there was a negative correlation of TSH-R-Ab levels with 25(OH)D levels in Graves disease patients with AO (r= - 0.53; р<0.05).
Keywords: autoimmune ophthalmopathy, Graves’ disease, vitamin D
References
1.Oliinyk VA, Terekhovа HM, Buldygina YuV, Fed’ko TV, Klochkova VM, Rakov OV, Lysova ZH. [Treatment of autoimmune ophthalmopathy in patients with diffuse toxic goiter by glucocorticoids]. Endokrynologiia. 2017;22(2):108–14. Ukrainian.
2.Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, et al. The 2016 European Thyroid Association/European Group on Graves' Orbitopathy Guidelines for the Management of Graves' Orbitopathy. Eur Thyroid J. 2016 Mar;5(1):9–26.
3.Kahaly GJ, Bartalena L, Heged?s L, Leenhardt L, Poppe K, Pearce SH. 2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism. Eur Thyroid J. 2018 Aug;7(4):167–86.
4.Smith TJ, Janssen JAMJL. Insulin-like growth factor-I receptor and thyroid-associated ophthalmopathy. Endocr Rev. 2019 Feb 1;40(1):236–67.
5.Kim D. The role of vitamin D in thyroid diseases. Int J Mol Sci. 2017 Sep; 18(9): 1949.
6.Ferrari SM, Fallahi P, Antonelli A, Benvenga S. Environmental issues in thyroid diseases. Front Endocrinol (Lausanne). 2017;8:50.
7.Nettore IC, Albano L, Ungaro P, Colao A, Macchia PE. Sunshine vitamin and thyroid. Rev Endocr Metab Disord. 2017 Jan14; 18(3).
8.Sassi F, Tamone C, D’Amelio P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018 Nov 3; 10(11): pii: E1656.
9.D'Aurizio F, Villalta D, Metus P, Doretto P, Tozzoli R. Is vitamin D a player or not in the pathophysiology of autoimmune thyroid diseases? Autoimmun Rev. 2015 May;14(5):363–9.
10.Muscogiuri G, Tirabassi G, Bizzaro G, Orio F, Paschou SA, Vryonidou A, et al. Vitamin D and thyroid disease: to D or not to D? Eur J Clin Nutr. 2015 Mar;69(3):291–96.
11.Wu D, Lewis ED, Pae M, Meydani SN. Nutritional modulation of immune function: analysis of evidence, mechanisms, and clinical relevance. Front Immunol. 2018; 9: 3160.
12.Umar M, Sastry KS, Chouchane AI. Role of vitamin D beyond the skeletal function: a review of the molecular and clinical studies. Int J Mol Sci. 2018 Jun; 19(6): pii: E1618.
13.Chekman IS, Gorchakova NO, Berezhniy VV, Davydiuk AV, Roman’ko MR. [Pharmacology of vitamin D]. Sovremennaia pediatriia. 2017; 2(82):28–36. Ukrainian.
14.Vondra K, St?rka L, Hampl R. Vitamin D and thyroid diseases. Physiol Res. 2015;64 Suppl 2:95–100.
15.Merrill SJ, Minucci SB. Thyroid autoimmunity: an interplay of factors. Vitam Horm. 2018;106:129–45.
16.Yoon SY, Bae SH, Shin YJ, Park ShG, Hwang S-H, Hyon JY, Wee WR. Low Serum 25-Hydroxyvitamin D Levels Are Associated with Dry Eye Syndrome. PLoS One. 2016; 11(1): e0147847.
17.Meng YF, Lu J, Xing Q, Tao JJ, Xiao P. Lower serum vitamin D level was associated with risk of dry eye syndrome. Med Sci Monit. 2017 May 10;23:2211–6.
18.Jin KW, Ro JW, ShinYJ, Hyon JY. Correlation of vitamin D levels with tear film stability and secretion in patients with dry eye syndrome. Acta Ophthalmol. 2017 May; 95(3):e230-e235.
19.Jeon D-H, Yeom H, Yang J, Song JS, Lee HK, Kim HCh. Are serum vitamin D levels associated with dry eye disease? Results from the Study Group for Environmental Eye Disease. J Prev Med Public Health. 2017 Nov;50(6):369–76.
20.Jee D, Kang S, Yuan Ch, Eunyoung Cho E, Arroyo JG, and The Epidemiologic survey Committee of the Korean Ophthalmologic Society. Serum 25-hydroxyvitamin D levels and dry eye syndrome: differential effects of vitamin D on ocular diseases. PLoS One. 2016; 11(2): e0149294.
21.Selter JH, Gire AI, Sikder S. The relationship between Graves’ ophthalmopathy and dry eye syndrome. Clin Ophthalmol. 2015; 9: 57–62.
22.Wang J, Lv S, Chen G, Gao C, He J, Zhong H, Xu Y. Meta-analysis of the association between vitamin D and autoimmune thyroid disease. Nutrients. 2015 Apr 3;7(4):2485–98.
23.Altieri B, Muscogiuri G, Barrea L, Mathieu C, Vallone CV, Mascitelli L, et al. Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept. Rev Endocr Metab Disord. 2017 Sep;18(3):335–46.
24.Chaudhary S, Dutta D, Kumar M, Saha S, Mondal SA, Kumar A, Mukhopadhyay S. Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: An open-labeled randomized controlled trial. Indian J Endocrinol Metab. 2016 May-Jun; 20(3): 391–8.
25.Simsek Y, Cakir I, Yetmis M, Dizdar OS, Baspinar O, Gokay F. Effects of vitamin D treatment on thyroid autoimmunity. J Res Med Sci. 2016; 21(6): 85.
26.Chahardoli R, Saboor-Yaraghi AA, Amouzegar A, Khalili D, Vakili AZ, Azizi F. Can supplementation with vitamin D modify thyroid autoantibodies (Anti-TPO Ab, Anti-Tg Ab) and thyroid profile (T3, T4, TSH) in Hashimoto's thyroiditis? A double blind, randomized clinical trial. Horm Metab Res. 2019 May;51(5):296–301.
27.Krysiak R, Kowalcze K, Okopie? B. Selenomethionine potentiates the impact of vitamin D on thyroid autoimmunity in euthyroid women with Hashimoto's thyroiditis and low vitamin D status. Pharmacol Rep. 2019 Apr;71(2):367–73.
28.Kivity Sh, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Dank? K, et al. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol. 2011 May; 8(3): 243–7.
29.Zhang H, Liang L, Xie Z. Low vitamin D status is associated with increased thyrotropin-receptor antibody titer in Graves disease. Endocr Pract. 2015 Mar;21(3):258–63.
30.Muscogiuri G, Mari D, Prolo S, Fatti LM, Cantone MC, Garagnani P, et al. 25 hydroxyvitamin D deficiency and its relationship to autoimmune thyroid disease in the elderly. Int J Environ Res Public Health. 2016 Aug 26;13(9).
31.Yasuda T, Okamoto Y, Hamada N, Miyashit K, Takahara M, Sakamoto F, et al. Serum vitamin D levels are decreased and associated with thyroid volume in female patients with newly onset Graves’ disease. Endocrine. 2012 Dec;42(3):739–41.
32.Xu M-Y, Cao B, Yin J, Wang D-F, Chen K-L, Lu Q-B. Vitamin D and Graves’ disease: a meta-analysis update. Nutrients. 2015 May; 7(5): 3813–27.
33.Planck T, Shahida B, Malm J, Manjer J. Vitamin D in Graves Disease: Levels, Correlation with Laboratory and Clinical Parameters, and Genetics. Eur Thyroid J. 2018 Jan;7(1):27-33.
34.Yasuda T, Okamoto Y, Hamada N, Miyashita K, Takahara M, Sakamoto F, et al. Serum vitamin D levels are decreased in patients without remission of Graves’ disease. Endocrine. 2013 Feb; 43(1): 230–2.
35.Ma J, Wu D, Li C, Fan C, Chao N, Liu J, et al. Lower serum 25-hydroxyvitamin D level is associated with 3 types of autoimmune thyroid diseases. Medicine (Baltimore). 2015 Sep;94(39):e1639.
36.Mangaraj S, Choudhury AK, Swain BM, Sarangi PK, Mohanty BK, Baliarsinha AK. Evaluation of vitamin D status and its impact on thyroid related parameters in new onset Graves' disease- A cross-sectional observational study. Indian J Endocr Metab. 2019;23:35–9.
37.Ke W, Sun T, Zhang Y, He L, Wu Q, Liu J, Zha B. 25-hydroxyvitamin D serum level in Hashimoto's thyroiditis, but not Graves' disease is relatively deficient. Endocr J. 2017 Jun 29;64(6):581–7.
38.P?udowski P, Karczmarewicz E, Bayer M, Carter G, Chlebna-Sok?? D, Czech-Kowalska J, et al. Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe – recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency. Endokrynol Pol. 2013;64(4):319–27.
Conflict of Interest: The authors declare that there are no conflicts of interest regarding this study and the publication of this article.