Effects of vitamin D in thyroid autoimmune pathologies: literature review and own data
Keywords:vitamin D, thyroid gland, autoimmune diseases, immune system
Background. Vitamin D (VD) is a versatile steroid hormone that regulates the activity of several thousand genes. Over the past decades, numerous diseases associated with VD deficiency have been reported, including cancer and autoimmune thyroid disorders. Researches revealed that VD can influence the development and course of these diseases. The VD participation in modulation of the hypothalamus-pituitary-thyroid gland axis, both at the level of the pituitary gland and at that of the thyroid, has been shown. The effect of VD on autoimmune diseases, including thyroid autoimmune diseases, is widely studied. Most of the
existing data support the relationship between VD deficiency and a greater tendency to develop and higher antibody titers associated with Hashimoto’s thyroiditis, Graves’ disease (GD) and postpartum thyroiditis. An important fact is that epidemiological studies have demonstrated a high prevalence of VD deficiency or insufficiency throughout the world. VD insufficiency is a potent dietary trigger that results in severe, chronic diseases. The question arises how reliable is the relationship between VD and autoimmune thyroid diseases (AITD). Although the results of the studies performed are somewhat contradictory, the vast majority of data indicates a link between VD deficiency and an increased risk of developing the disease, high antibody titers, and difficulties in treatment. Genetic polymorphisms associated with VD function and metabolism also have some influence on the risk of ATD. With regard to the precise nature of the relationship between VD and AITD, it is believed that VD plays a small but significant role in the AITD pathogenesis. After the AITD development, its consequence may be an increase in VD deficiency. It is the need to determine the effect of VD supplementation in the prevention and treatment of AITD and its optimal level directly for clinical practice. It is necessary for clinical practice to determine the effect of VD supplements in the prevention and treatment of AITD and its optimal level. A study, the purpose of which was to study the content of VD, namely 25(OH)D in 176 patients with GD complicated by autoimmune ophthalmopathy (AO) and to identify a correlation relationship with antithyroid antibodies (TPO, TSHR-Ab) was carried out at the State Institution “V.P. Komissarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine”. Materials and methods. The levels of 25(OH)D, TSH, TSHR-Ab, TPO were determined by enzyme immunoassay using standard kits from Siemens firm. During the study, 176 patients were divided into two groups, depending on the presence of AO: the first group consisted of patients with GD without AO (62 people), the second group included patients with GD and AO (114 people). Results. In GD, 91.78 % of patients (161 people) have an insufficient level of 25(OH)D content: a suboptimal level was recorded in 42 patients (23.86 %), and a deficit — in 119 patients (67.61 %). A significant negative correlation relationship was revealed between TSHR-Ab and 25(OH)D in the group of patients with GD and AO — with a lower level of 25(OH)D, the higher values of TSHR-Ab correlate. Compensation of the 25(OH)D deficiency leads to a significant (P < 0.05) decrease in the levels of TSHR-Ab and TPO in patients with GD. Besides, there is a large body of literature available lin-king vitamin D to thyroid autoimmunity as a result of cross-sectional studies and observations. Conclusions. Thus, there is still an urgent need for large multicenter studies to evaluate the effect of vitamin D supplementation on meaningful long-term clinical endpoints in AITD.
Balla M, Merugu GP, Konala VM, et al. Back to basics: review on vitamin D and respiratory viral infections including COVID-19. J Community Hosp Intern Med Perspect. 2020 Oct 29;10(6):529-536. doi:10.1080/20009666.2020.1811074.
Kumar R, Rathi H, Haq A, Wimalawansa SJ, Sharma A. Putative roles of vitamin D in modulating immune response and immunopathology associated with COVID-19. Virus Res. 2021 Jan 15;292:198235. doi:10.1016/j.virusres.2020.198235.
Ferreira GB, Vanherwegen AS, Eelen G, et al. Vitamin D3 Induces Tolerance in Human Dendritic Cells by Activation of Intracellular Metabolic Pathways. Cell Rep. 2015 Feb 10;10(5):711-725. doi:10.1016/j.celrep.2015.01.013.
Zhang X, Zhou M, Guo Y, Song Z, Liu B. 1,25-Dihydroxyvitamin D₃ Promotes High Glucose-Induced M1 Macrophage Switching to M2 via the VDR-PPARγ Signaling Pathway. Biomed Res Int. 2015;2015:157834. doi:10.1155/2015/157834.
Rak K, Bronkowska M. Immunomodulatory Effect of Vitamin D and Its Potential Role in the Prevention and Treatment of Type 1 Diabetes Mellitus-A Narrative Review. Molecules. 2018 Dec 24;24(1):53. doi:10.3390/molecules24010053.
Piantoni S, Andreoli L, Scarsi M, et al. Phenotype modifications of T-cells and their shift toward a Th2 response in patients with systemic lupus erythematosus supplemented with different monthly regimens of vitamin D. Lupus. 2015 Apr;24(4-5):490-8. doi:10.1177/0961203314559090.
Barchetta I, Baroni MG, Leonetti F, et al. TSH levels are associated with vitamin D status and seasonality in an adult population of euthyroid adults. Clin Exp Med. 2015 Aug;15(3):389-96. doi:10.1007/s10238-014-0290-9.
Kim M, Song E, Oh HS, et al. Vitamin D deficiency affects thyroid autoimmunity and dysfunction in iodine-replete area: Korea national health and nutrition examination survey. Endocrine. 2017 Nov;58(2):332-339. doi:10.1007/s12020-017-1425-z.
Vondra K, Bílek R, Matucha P, et al. Vitamin D supplementation changed relationships, not levels of metabolic-hormonal parameters in autoimmune thyroiditis. Physiol Res. 2017 Sep 26;66(Suppl 3):S409-S417. doi:10.33549/physiolres.933727.
Dutta D, Sharma M, Aggarwal S, Mohindra R, Bhattacharya S, Kalra S. Vitamin D, Thyroid Autoimmunity and Cancer: An Interplay of Different Factors. Indian J Endocrinol Metab. 2019 Sep-Oct;23(5):507-513. doi:10.4103/ijem.IJEM_526_19.
Muscogiuri G, Palomba S, Caggiano M, Tafuri D, Colao A, Orio F. Low 25 (OH) vitamin D levels are associated with autoimmune thyroid disease in polycystic ovary syndrome. Endocrine. 2016 Aug;53(2):538-42. doi:10.1007/s12020-015-0745-0.
Effraimidis G, Badenhoop K, Tijssen JG, Wiersinga WM. Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur J Endocrinol. 2012 Jul;167(1):43-8. doi:10.1530/EJE-12-0048.
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. doi:10.1016/j.autrev.2014.10.008.
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. doi:10.1055/a-0856-1044.
Kaminskyi OV, Pankiv VI, Pankiv IV, Afanasyev DE. Vitamin D Content In Population Of Radiologically Contaminated Areas In Chernivtsi Oblast (pilot project). Probl Radiac Med Radiobiol. 2018 Dec;23:442-451. doi:10.33145/2304-8336-2018-23-442-451. (in Ukrainian).
Povorozniuk VV, Pankiv IV. Intercommunication between vitamin D deficiency and thyroid hypofunction. Clinical Endocrinology and Endocrine Surgery. 2014;3-4(48):12-16. doi:10.24026/1818-1384.3-4(48).2014.75353. (in Ukrainian).
Goswami R, Marwaha RK, Gupta N, et al. Prevalence of vitamin D deficiency and its relationship with thyroid autoimmunity in Asian Indians: a community-based survey. Br J Nutr. 2009 Aug;102(3):382-6. doi:10.1017/S0007114509220824.
Yasuda T, Okamoto Y, Hamada N, 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. doi:10.1007/s12020-012-9679-y.
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 Endocrinol Metab. 2019 Jan-Feb;23(1):35-39. doi:10.4103/ijem.IJEM_183_18.
Ahn HY, Chung YJ, Cho BY. Serum 25-hydroxyvitamin D might be an independent prognostic factor for Graves disease recurrence. Medicine (Baltimore). 2017 Aug;96(31):e7700. doi:10.1097/MD.0000000000007700.
Li X, Wang G, Lu Z, Chen M, Tan J, Fang X. Serum 25-hydroxyvitamin D predict prognosis in radioiodine therapy of Graves' disease. J Endocrinol Invest. 2015 Jul;38(7):753-9. doi:10.1007/s40618-015-0252-4.
Pankiv VI, Yuzvenko TYu, Pankiv IV. Type 2 diabetes mellitus and subclinical hypothyroidism: focusing on the role of cholecalciferol. Problems of Endocrine Pathology. 2019;68(2):46-51. doi:10.21856/j-PEP.2019.2.07.
Gao XR, Yu YG. Meta-Analysis of the Association between Vitamin D Receptor Polymorphisms and the Risk of Autoimmune Thyroid Disease. Int J Endocrinol. 2018 Mar 22;2018:2846943. doi:10.1155/2018/2846943.
Giovinazzo S, Vicchio TM, Certo R, et al. Vitamin D receptor gene polymorphisms/haplotypes and serum 25(OH)D3 levels in Hashimoto's thyroiditis. Endocrine. 2017 Feb;55(2):599-606. doi:10.1007/s12020-016-0942-5.
Veneti S, Anagnostis P, Adamidou F, Artzouchaltzi AM, Boboridis K, Kita M. Association between vitamin D receptor gene polymorphisms and Graves' disease: a systematic review and meta-analysis. Endocrine. 2019 Aug;65(2):244-251. doi:10.1007/s12020-019-01902-3.
Inoue N, Watanabe M, Ishido N, et al. The functional polymorphisms of VDR, GC and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases. Clin Exp Immunol. 2014 Nov;178(2):262-9. doi:10.1111/cei.12420.
Wang S, Wu Y, Zuo Z, Zhao Y, Wang K. The effect of vitamin D supplementation on thyroid autoantibody levels in the treatment of autoimmune thyroiditis: a systematic review and a meta-analysis. Endocrine. 2018 Mar;59(3):499-505. doi:10.1007/s12020-018-1532-5.
Krysiak R, Kowalcze K, Okopień B. The effect of vitamin D on thyroid autoimmunity in euthyroid men with autoimmune thyroiditis and testosterone deficiency. Pharmacol Rep. 2019 Oct;71(5):798-803. doi:10.1016/j.pharep.2019.04.010.
Krysiak R, Kowalcze K, Okopień 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):367-373. doi:10.1016/j.pharep.2018.12.006.
Mirhosseini N, Brunel L, Muscogiuri G, Kimball S. Physiological serum 25-hydroxyvitamin D concentrations are associated with improved thyroid function-observations from a community-based program. Endocrine. 2017 Dec;58(3):563-573. doi:10.1007/s12020-017-1450-y.
Grove-Laugesen D, Malmstroem S, Ebbehoj E, et al. Effect of 9 months of vitamin D supplementation on arterial stiffness and blood pressure in Graves' disease: a randomized clinical trial. Endocrine. 2019 Nov;66(2):386-397. doi:10.1007/s12020-019-01997-8.
Krysiak R, Szkróbka W, Okopień B. The Effect of Vitamin D on Thyroid Autoimmunity in Levothyroxine-Treated Women with Hashimoto's Thyroiditis and Normal Vitamin D Status. Exp Clin Endocrinol Diabetes. 2017 Apr;125(4):229-233. doi:10.1055/s-0042-123038.
Kozai M, Yamamoto H, Ishiguro M, et al. Thyroid hormones decrease plasma 1α,25-dihydroxyvitamin D levels through transcriptional repression of the renal 25-hydroxyvitamin D3 1α-hydroxylase gene (CYP27B1). Endocrinology. 2013 Feb;154(2):609-22. doi:10.1210/en.2012-1647.
Botelho IMB, Moura Neto A, Silva CA, Tambascia MA, Alegre SM, Zantut-Wittmann DE. Vitamin D in Hashimoto's thyroiditis and its relationship with thyroid function and inflammatory status. Endocr J. 2018 Oct 29;65(10):1029-1037. doi:10.1507/endocrj.EJ18-0166.
Jyotsna VP, Sahoo A, Ksh SA, Sreenivas V, Gupta N. Bone mineral density in patients of Graves disease pre- & post-treatment in a predominantly vitamin D deficient population. Indian J Med Res. 2012;135(1):36-41. doi:10.4103/0971-5916.93422.
Proal AD, Albert PJ, Marshall TG. Dysregulation of the vitamin D nuclear receptor may contribute to the higher prevalence of some autoimmune diseases in women. Ann N Y Acad Sci. 2009 Sep;1173:252-9. doi:10.1111/j.1749-6632.2009.04672.x.
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