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Reviews in Endocrine and Metabolic Disorders

, Volume 18, Issue 3, pp 335–346 | Cite as

Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept

  • Barbara AltieriEmail author
  • Giovanna Muscogiuri
  • Luigi Barrea
  • Chantal Mathieu
  • Carla V. Vallone
  • Luca Mascitelli
  • Giorgia Bizzaro
  • Vincenzo M. Altieri
  • Giacomo Tirabassi
  • Giancarlo Balercia
  • Silvia Savastano
  • Nicola Bizzaro
  • Cristina L. Ronchi
  • Annamaria Colao
  • Alfredo Pontecorvi
  • Silvia Della Casa
Article

Abstract

In the last few years, more attention has been given to the “non-calcemic” effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison’s disease, Hashimoto’s thyroiditis, Graves’ disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

Keywords

Vitamin D Autoimmunity Type 1 diabetes mellitus Addison’s disease Hashimoto’s thyroiditis Graves’ disease Autoimmune polyendocrine syndromes Environment Lifestyle 

Notes

Authors contribution

B.A. and G.M. designed the study. B.A., G.M., L.B., C.M., C.V.V., L.M. and G.B. participated in the literature search and performed the selection of studies. B.A. wrote the Introduction, Methods and the Conclusion of the review, as well as the paragraphs on Addison’s disease and on vitamin D supplementation. C.V.V. supported B.A. in writing the Introduction and the paragraphs on vitamin D supplementation. G.M., S.S., N.B. and C.L.R. collaborated to the preparation of the manuscript providing relevant suggestions and corrections according to their long-lasting expertise in different research fields. L.B. wrote the paragraph on Grave’s disease and autoimmune polyendocrine syndromes. C.M. wrote the paragraph on diabetes mellitus. L.M. prepared the figure and wrote the paragraph on clinical and basic evidence. G.B. wrote the paragraph on Hashimoto thyroiditis. V.M.A., G.T. and G.B. contributed to the final version of the manuscript. A.C., A.P. and S.D.C. coordinated and supervised the preparation of the manuscript. All the authors reviewed and approved the final version of the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Aranow C. Vitamin D, and the immune system. J Investig Med Off Publ Am Fed Clin Res. 2011;59(6):881–6. doi: 10.2310/JIM.0b013e31821b8755.Google Scholar
  2. 2.
    Bikle DD. Vitamin D, metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319–29. doi: 10.1016/j.chembiol.2013.12.016.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Holick MF. Vitamin D, deficiency. New Engl J Med. 2007;357(3):266–81. doi: 10.1056/NEJMra070553.PubMedCrossRefGoogle Scholar
  4. 4.
    Battault S, Whiting SJ, Peltier SL, Sadrin S, Gerber G, Maixent JM. Vitamin D metabolism, functions, and needs: from science to health claims. Eur J Nutr. 2013;52(2):429–41. doi: 10.1007/s00394-012-0430-5.PubMedCrossRefGoogle Scholar
  5. 5.
    Muscogiuri G, Mitri J, Mathieu C, Badenhoop K, Tamer G, Orio F, et al. Mechanisms in endocrinology: vitamin D as a potential contributor in endocrine health and disease. Eur J Endocrinol / Eur Fed Endocr Soc. 2014;171(3):R101–10. doi: 10.1530/EJE-14-0158.CrossRefGoogle Scholar
  6. 6.
    Muscogiuri G, Altieri B, Annweiler C, Balercia G, Pal HB, Boucher BJ, et al. Vitamin D and chronic diseases: the current state of the art. Arch Toxicol. 2016. doi: 10.1007/s00204-016-1804-x.Google Scholar
  7. 7.
    Altieri B, Grant WB, Casa SD, Orio F, Pontecorvi A, Colao A, et al. Vitamin D and pancreas: the role of sunshine vitamin in the pathogenesis of diabetes mellitus and pancreatic cancer. Crit Rev Food Sci Nutr. 2016. doi: 10.1080/10408398.2015.1136922.Google Scholar
  8. 8.
    Moukayed M, Grant WB. Molecular link between vitamin D and cancer prevention. Nutrients. 2013;5(10):3993–4021. doi: 10.3390/nu5103993.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab. 2009;94(1):26–34. doi: 10.1210/jc.2008-1454.PubMedCrossRefGoogle Scholar
  10. 10.
    Hewison M, Gacad MA, Lemire J, Adams JS. Vitamin D as a cytokine and hematopoetic factor. Rev Endocr Metab Disord. 2001;2(2):217–27.PubMedCrossRefGoogle Scholar
  11. 11.
    van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005;97(1/2):93–101. doi: 10.1016/j.jsbmb.2005.06.002.PubMedCrossRefGoogle Scholar
  12. 12.
    Hossein-Nezhad A, Spira A, Holick MF. Influence of vitamin D status and vitamin D3 supplementation on genome wide expression of white blood cells: a randomized double-blind clinical trial. PLoS One. 2013;8(3):e58725. doi: 10.1371/journal.pone.0058725.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin N Am. 2010;39(2):365–79. doi: 10.1016/j.ecl.2010.02.010.CrossRefGoogle Scholar
  14. 14.
    Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 2013;5(7):2502–21. doi: 10.3390/nu5072502.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Kearns MD, Alvarez JA, Seidel N, Tangpricha V. Impact of vitamin D on infectious disease. Am J Med Sci. 2015;349(3):245–62. doi: 10.1097/MAJ.0000000000000360.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Eendocrinol. 2014;2(1):76–89. doi: 10.1016/S2213-8587(13)70165-7.CrossRefGoogle Scholar
  17. 17.
    Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med (Berlin). 2010;88(5):441–50. doi: 10.1007/s00109-010-0590-9.CrossRefGoogle Scholar
  18. 18.
    Rosen Y, Daich J, Soliman I, Brathwaite E, Shoenfeld Y. Vitamin D and autoimmunity. Scand J Rheumatol 2016:1–9 doi: 10.3109/03009742.2016.1151072.
  19. 19.
    Borges MC, Martini LA, Rogero MM. Current perspectives on vitamin D, immune system, and chronic diseases. Nutrition. 2011;27(4):399–404. doi: 10.1016/j.nut.2010.07.022.PubMedCrossRefGoogle Scholar
  20. 20.
    Grad R. Cod and the consumptive: a brief history of cod-liver oil in the treatment of pulmonary tuberculosis. Pharm Hist. 2004;46(3):106–20.PubMedGoogle Scholar
  21. 21.
    Griffin MD, Lutz WH, Phan VA, Bachman LA, McKean DJ, Kumar R. Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs. Biochem Biophys Res Commun. 2000;270(3):701708. doi: 10.1006/bbrc.2000.2490.CrossRefGoogle Scholar
  22. 22.
    Bartley J. Vitamin D: emerging roles in infection and immunity. Expert Rev Anti-Infect Ther. 2010;8(12):1359–69. doi: 10.1586/eri.10.102.PubMedCrossRefGoogle Scholar
  23. 23.
    Kivity S, Agmon-Levin N, Blank M, Shoenfeld Y. Infections and autoimmunity—friends or foes? Trends Immunol. 2009;30(8):409–14. doi: 10.1016/j.it.2009.05.005.PubMedCrossRefGoogle Scholar
  24. 24.
    Borella E, Nesher G, Israeli E, Shoenfeld Y. Vitamin D: a new anti-infective agent? Ann NY Acad Sci. 2014;1317:76–83. doi: 10.1111/nyas.12321.PubMedCrossRefGoogle Scholar
  25. 25.
    Yenamandra SP, Lundin A, Arulampalam V, Yurchenko M, Pettersson S, Klein G, et al. Expression profile of nuclear receptors upon Epstein–Barr virus induced B cell transformation. Exp Oncol. 2009;31(2):92–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Bizzaro G, Shoenfeld Y. Vitamin D and autoimmune thyroid diseases: facts and unresolved questions. Immunol Res. 2015;61(1/2):46–52. doi: 10.1007/s12026-014-8579-z.PubMedCrossRefGoogle Scholar
  27. 27.
    Dimeloe S, Nanzer A, Ryanna K, Hawrylowicz C. Regulatory T cells, inflammation, and the allergic response—The role of glucocorticoids and Vitamin D. J S Biochem Mol Biol. 2010;120(2/3):86–95. doi: 10.1016/j.jsbmb.2010.02.029.CrossRefGoogle Scholar
  28. 28.
    Figueiredo AS, Schumacher A. The T helper type 17/regulatory T cell paradigm in pregnancy. Immunology. 2016;148(1):13–21. doi: 10.1111/imm.12595.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Ullah MI, Koch CA, Tamanna S, Rouf S, Shamsuddin L. Vitamin D deficiency and the risk of preeclampsia and eclampsia in Bangladesh. Hormone Metab Res [Hormon- und Stoffwechselforschung] [Hormones et metabolisme]. 2013;45(9):682–7. doi: 10.1055/s-0033-1345199.CrossRefGoogle Scholar
  30. 30.
    Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol. 2007;179(3):1634–47.PubMedCrossRefGoogle Scholar
  31. 31.
    Zhang J, Li W, Liu J, Wu W, Ouyang H, Zhang Q, et al. Polymorphisms in the vitamin D receptor gene and type 1 diabetes mellitus risk: an update by meta-analysis. Mol Cell Endocrinol. 2012;355(1):135–42. doi: 10.1016/j.mce.2012.02.003.PubMedCrossRefGoogle Scholar
  32. 32.
    Ban Y, Taniyama M, Yanagawa T, Yamada S, Maruyama T, Kasuga A. Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population. BMC Med Genet. 2001;2:7.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Kahles H, Morahan G, Todd JA, Badenhoop K. Association analyses of the vitamin D receptor gene in 1654 families with type I diabetes. Genes Immun. 2009;10 Suppl 1:S60–3. doi: 10.1038/gene.2009.93.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    van Etten E, Verlinden L, Giulietti A, Ramos-Lopez E, Branisteanu DD, Ferreira GB, et al. The vitamin D receptor gene FokI polymorphism: functional impact on the immune system. Eur J Immunol. 2007;37(2):395–405. doi: 10.1002/eji.200636043.PubMedCrossRefGoogle Scholar
  35. 35.
    Moltchanova EV, Schreier N, Lammi N, Karvonen M. Seasonal variation of diagnosis of type 1 diabetes mellitus in children worldwide. Diabet Med. 2009;26(7):673–8. doi: 10.1111/j.1464-5491.2009.02743.x.PubMedCrossRefGoogle Scholar
  36. 36.
    Stene LC, Ulriksen J, Magnus P, Joner G. Use of cod liver oil during pregnancy associated with lower risk of type I diabetes in the offspring. Diabetologia. 2000;43(9):1093–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Stene LC, Joner G. Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. Am J Clin Nutr. 2003;78(6):1128–34.PubMedGoogle Scholar
  38. 38.
    Marjamaki L, Niinisto S, Kenward MG, Uusitalo L, Uusitalo U, Ovaskainen ML, et al. Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring. Diabetologia. 2010;53(8):1599–607. doi: 10.1007/s00125-010-1734-8.PubMedCrossRefGoogle Scholar
  39. 39.
    Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Arch Dis Child. 2008;93(6):512–7. doi: 10.1136/adc.2007.128579.PubMedCrossRefGoogle Scholar
  40. 40.
    Wolden-Kirk H, Rondas D, Bugliani M, Korf H, Van Lommel L, Brusgaard K, et al. Discovery of molecular pathways mediating 1,25-dihydroxyvitamin D3 protection against cytokine-induced inflammation and damage of human and male mouse islets of Langerhans. Endocrinology. 2014;155(3):736–47. doi: 10.1210/en.2013-1409.PubMedCrossRefGoogle Scholar
  41. 41.
    Wolden-Kirk H, Overbergh L, Christesen HT, Brusgaard K, Mathieu C. Vitamin D and diabetes: its importance for beta cell and immune function. Mol Cell Endocrinol. 2011;347(1/2):106–20. doi: 10.1016/j.mce.2011.08.016.PubMedCrossRefGoogle Scholar
  42. 42.
    Pitocco D, Crino A, Di Stasio E, Manfrini S, Guglielmi C, Spera S, et al. The effects of calcitriol and nicotinamide on residual pancreatic beta-cell function in patients with recent-onset Type 1 diabetes (IMDIAB XI). Diabetes Med. 2006;23(8):920–3. doi: 10.1111/j.1464-5491.2006.01921.x.CrossRefGoogle Scholar
  43. 43.
    Papadimitriou DT, Marakaki C, Fretzayas A, Nicolaidou P, Papadimitriou A. Negativation of type 1 diabetes-associated autoantibodies to glutamic acid decarboxylase and insulin in children treated with oral calcitriol. J Diabetes. 2013;5(3):344–8. doi: 10.1111/1753-0407.12023.PubMedCrossRefGoogle Scholar
  44. 44.
    Li X, Liao L, Yan X, Huang G, Lin J, Lei M, et al. Protective effects of 1-alpha-hydroxyvitamin D3 on residual beta-cell function in patients with adult-onset latent autoimmune diabetes (LADA). Diabetes/Met Res Rev. 2009;25(5):411–6. doi: 10.1002/dmrr.977.CrossRefGoogle Scholar
  45. 45.
    Walter M, Kaupper T, Adler K, Foersch J, Bonifacio E, Ziegler AG. No effect of the 1alpha,25-dihydroxyvitamin D3 on beta-cell residual function and insulin requirement in adults with new-onset type 1 diabetes. Diabetes Care. 2010;33(7):1443–8. doi: 10.2337/dc09-2297.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Michels AW, Eisenbarth GS. Autoimmune polyendocrine syndrome type 1 (APS-1) as a model for understanding autoimmune polyendocrine syndrome type 2 (APS-2). J Intern Med. 2009;265(5):530–40. doi: 10.1111/j.1365-2796.2009.02091.x.PubMedCrossRefGoogle Scholar
  47. 47.
    Bratland E, Husebye ES. Cellular immunity and immunopathology in autoimmune Addison’s disease. Mol Cell Endocrinol. 2011;336(1/2):180–90. doi: 10.1016/j.mce.2010.12.015.PubMedCrossRefGoogle Scholar
  48. 48.
    Pani MA, Seissler J, Usadel KH, Badenhoop K. Vitamin D receptor genotype is associated with Addison’s disease. Eur J Endocrinol / Eur Fed Endocr Soc. 2002;147(5):635–40.CrossRefGoogle Scholar
  49. 49.
    Lopez ER, Zwermann O, Segni M, Meyer G, Reincke M, Seissler J, et al. A promoter polymorphism of the CYP27B1 gene is associated with Addison’s disease, Hashimoto’s thyroiditis, Graves’ disease, and type 1 diabetes mellitus in Germans. Eur J Endocrinol / Eur Fed Endocr Soc. 2004;151(2):193–7.CrossRefGoogle Scholar
  50. 50.
    Fichna M, Zurawek M, Januszkiewicz-Lewandowska D, Gryczynska M, Fichna P, Sowinski J. Association of the CYP27B1 C(-1260)A polymorphism with autoimmune Addison’s disease. Exp Clin Endocrinol Diabetes Off J German Soc Endocrinol German Diabetes Assoc. 2010;118(8):544–9. doi: 10.1055/s-0029-1241206.CrossRefGoogle Scholar
  51. 51.
    Jennings CE, Owen CJ, Wilson V, Pearce SH. A haplotype of the CYP27B1 promoter is associated with autoimmune Addison’s disease but not with Graves’ disease in a UK population. J Mol Endocrinol. 2005;34(3):859–63. doi: 10.1677/jme.1.01760.PubMedCrossRefGoogle Scholar
  52. 52.
    Gittoes NJ. Vitamin D—what is normal according to latest research and how should we deal with it? Clin Med. 2016;16(2):171–4. doi: 10.7861/clinmedicine.16-2-171.CrossRefGoogle Scholar
  53. 53.
    Ramagopalan SV, Goldacre R, Disanto G, Giovannoni G, Goldacre MJ. Hospital admissions for vitamin D-related conditions and subsequent immune-mediated disease: record-linkage studies. BMC Med. 2013;11:171. doi: 10.1186/1741-7015-11-171.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Bellastella G, Maiorino MI, Petrizzo M, De Bellis A, Capuano A, Esposito K, et al. Vitamin D and autoimmunity: what happens in autoimmune polyendocrine syndromes? J Endocrinol Investig. 2015;38(6):629–33. doi: 10.1007/s40618-014-0233-z.CrossRefGoogle Scholar
  55. 55.
    Montoli A, Colussi G, Minetti L. Hypercalcaemia in Addison’s disease: calciotropic hormone profile and bone histology. J Intern Med. 1992;232(6):535–40.PubMedCrossRefGoogle Scholar
  56. 56.
    Suliman AM, Freaney R, Smith TP, McBrinn Y, Murray B, McKenna TJ. The impact of different glucocorticoid replacement schedules on bone turnover and insulin sensitivity in patients with adrenal insufficiency. Clin Endocrinol. 2003;59(3):380–7.CrossRefGoogle Scholar
  57. 57.
    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;69(3):291–6. doi: 10.1038/ejcn.2014.265.PubMedCrossRefGoogle Scholar
  58. 58.
    Wang J, Lv S, Chen G, Gao C, He J, Zhong H, et al. Meta-analysis of the association between vitamin D and autoimmune thyroid disease. Nutrients. 2015;7(4):2485–98. doi: 10.3390/nu7042485.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Sonmezgoz E, Ozer S, Yilmaz R, Onder Y, Butun I, Bilge S. Hypovitaminosis D in children with Hashimotos thyroiditis. Rev Med Chil. 2016;144(5):611–6. doi: 10.4067/S0034-98872016000500009.PubMedCrossRefGoogle Scholar
  60. 60.
    Muscogiuri G, Mari D, Prolo S, Fatti LM, Cantone MC, Garagnani P, et al. Hydroxyvitamin D deficiency and its relationship to autoimmune thyroid disease in the elderly. Int J Environ Res Public Health. 2016;13(9). doi: 10.3390/ijerph13090850.
  61. 61.
    Mazokopakis EE, Papadomanolaki MG, Tsekouras KC, Evangelopoulos AD, Kotsiris DA, Tzortzinis AA. Is vitamin D related to pathogenesis and treatment of Hashimoto’s thyroiditis? Hell J Nucl Med. 2015;18(3):222–7.PubMedGoogle Scholar
  62. 62.
    Maciejewski A, Wojcicka M, Roszak M, Losy J, Lacka K. Assessment of vitamin D level in autoimmune thyroiditis patients and a control group in the Polish population. Adv Clin Exp Med Off Organ Wroclaw Med Univ. 2015;24(5):801–6. doi: 10.17219/acem/29183.CrossRefGoogle Scholar
  63. 63.
    Chaudhary S, Dutta D, Kumar M, Saha S, Mondal SA, Kumar A, et al. 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;20(3):391–8. doi: 10.4103/2230-8210.179997.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Effraimidis G, Badenhoop K, Tijssen JG, Wiersinga WM. Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur J Endocrinol / Eur Fed Endocr Soc. 2012;167(1):43–8. doi: 10.1530/EJE-12-0048.CrossRefGoogle Scholar
  65. 65.
    Goswami R, Marwaha RK, Gupta N, Tandon N, Sreenivas V, Tomar 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;102(3):382–6. doi: 10.1017/S0007114509220824.PubMedCrossRefGoogle Scholar
  66. 66.
    Yasmeh J, Farpour F, Rizzo V, Kheradnam S, Sachmechi I. Hashimoto thyroiditis not associated with vitamin D deficiency. Endocr Pract Off J Am Coll Endocrinol Am Assoc Clin Endocrinol. 2016;22(7):809–13. doi: 10.4158/EP15934.OR.Google Scholar
  67. 67.
    Yazici D, Yavuz D, Tarcin O, Sancak S, Deyneli O, Akalin S. Vitamin D receptor gene ApaI, TaqI, FokI, and BsmI polymorphisms in a group of Turkish patients with Hashimoto’s thyroiditis. Minerva Endocrinol. 2013;38(2):195–201.PubMedGoogle Scholar
  68. 68.
    Inoue N, Watanabe M, Ishido N, Katsumata Y, Kagawa T, Hidaka Y, et al. The functional polymorphisms of VDR, GC, and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases. Clin Exp Immunol. 2014;178(2):262–9. doi: 10.1111/cei.12420.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Feng M, Li H, Chen SF, Li WF, Zhang FB. Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis. Endocrine. 2013;43(2):318–26. doi: 10.1007/s12020-012-9812-y.PubMedCrossRefGoogle Scholar
  70. 70.
    Giovinazzo S, Vicchio TM, Certo R, Alibrandi A, Palmieri O, Campenni A, et al. Vitamin D receptor gene polymorphisms/haplotypes and serum 25(OH)D3 levels in Hashimoto’s thyroiditis. Endocrine. 2016. doi: 10.1007/s12020-016-0942-5.Google Scholar
  71. 71.
    Agmon-Levin N, Theodor E, Segal RM, Shoenfeld Y. Vitamin D in systemic and organ-specific autoimmune diseases. Clin Rev Allergy Immunol. 2013;45(2):256–66. doi: 10.1007/s12016-012-8342-y.PubMedCrossRefGoogle Scholar
  72. 72.
    Cooper GS, Stroehla BC. The epidemiology of autoimmune diseases. Autoimmun Rev. 2003;2(3):119–25.PubMedCrossRefGoogle Scholar
  73. 73.
    Yasuda T, Okamoto Y, Hamada N, Miyashita 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;42(3):739–41. doi: 10.1007/s12020-012-9679-y.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Menconi F, Marcocci C, Marino M. Diagnosis and classification of Graves’ disease. Autoimmun Rev. 2014;13(4/5):398–402. doi: 10.1016/j.autrev.2014.01.013.PubMedCrossRefGoogle Scholar
  75. 75.
    Marino M, Latrofa F, Menconi F, Chiovato L, Vitti P. Role of genetic and non-genetic factors in the etiology of Graves’ disease. J Endocrinol Investig. 2015;38(3):283–94. doi: 10.1007/s40618-014-0214-2.CrossRefGoogle Scholar
  76. 76.
    Jurecka-Lubieniecka B, Bednarczuk T, Ploski R, Krajewska J, Kula D, Kowalska M, et al. Differences in gene–gene interactions in Graves’ disease patients stratified by age of onset. PLoS One. 2016;11(3):e0150307. doi: 10.1371/journal.pone.0150307.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Wiersinga WM. Thyroid autoimmunity. Endocr Dev. 2014;26:139–57. doi: 10.1159/000363161.PubMedCrossRefGoogle Scholar
  78. 78.
    Wiersinga WM. Clinical relevance of environmental factors in the pathogenesis of autoimmune thyroid disease. Endocrinol Metab. 2016;31(2):213–22. doi: 10.3803/EnM.2016.31.2.213.CrossRefGoogle Scholar
  79. 79.
    Xu MY, Cao B, Yin J, Wang DF, Chen KL, Lu QB. Vitamin D and Graves’ disease: a meta-analysis update. Nutrients. 2015;7(5):3813–27. doi: 10.3390/nu7053813.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Rotondi M, Chiovato L. Vitamin D deficiency in patients with Graves’ disease: probably something more than a casual association. Endocrine. 2013;43(1):3–5. doi: 10.1007/s12020-012-9776-y.PubMedCrossRefGoogle Scholar
  81. 81.
    Choi YM, Kim WG, Kim TY, Bae SJ, Kim HK, Jang EK, et al. Low levels of serum vitamin D3 are associated with autoimmune thyroid disease in premenopausal women. Thyroid Off J Am Thyroid Assoc. 2014;24(4):655–61. doi: 10.1089/thy.2013.0460.CrossRefGoogle Scholar
  82. 82.
    Van Belle TL, Gysemans C, Mathieu C. Vitamin D in autoimmune, infectious and allergic diseases: a vital player? Best Pract Res Clin Endocrinol Metab. 2011;25(4):617–32. doi: 10.1016/j.beem.2011.04.009.PubMedCrossRefGoogle Scholar
  83. 83.
    Zhou H, Xu C, Gu M. Vitamin D receptor (VDR) gene polymorphisms and Graves’ disease: a meta-analysis. Clin Endocrinol. 2009;70(6):938–45. doi: 10.1111/j.1365-2265.2008.03413.x.CrossRefGoogle Scholar
  84. 84.
    Cutolo M. Autoimmune polyendocrine syndromes. Autoimmun Rev. 2014;13(2):85–9. doi: 10.1016/j.autrev.2013.07.006.PubMedCrossRefGoogle Scholar
  85. 85.
    Lindmark E, Chen Y, Georgoudaki AM, Dudziak D, Lindh E, Adams WC, et al. AIRE expressing marginal zone dendritic cells balances adaptive immunity and T-follicular helper cell recruitment. J Autoimmun. 2013;42:62–70. doi: 10.1016/j.jaut.2012.11.004.PubMedCrossRefGoogle Scholar
  86. 86.
    Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–538. doi: 10.1210/jc.2010-2704.PubMedCrossRefGoogle Scholar
  87. 87.
    Aspray TJ, Bowring C, Fraser W, Gittoes N, Javaid MK, Macdonald H, et al. National Osteoporosis Society vitamin D guideline summary. Age Aging. 2014;43(5):592–5. doi: 10.1093/ageing/afu093.CrossRefGoogle Scholar
  88. 88.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. doi: 10.1210/jc.2011-0385.PubMedCrossRefGoogle Scholar
  89. 89.
    Hewison M. An update on vitamin D and human immunity. Clin Endocrinol. 2012;76(3):315–25. doi: 10.1111/j.1365-2265.2011.04261.x.CrossRefGoogle Scholar
  90. 90.
    Mathieu C, Waer M, Casteels K, Laureys J, Bouillon R. Prevention of type I diabetes in NOD mice by nonhypercalcemic doses of a new structural analog of 1,25-dihydroxyvitamin D3, KH1060. Endocrinology. 1995;136(3):866–72. doi: 10.1210/endo.136.3.7867594.PubMedCrossRefGoogle Scholar
  91. 91.
    Antico A, Tampoia M, Tozzoli R, Bizzaro N. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev. 2012;12(2):127–36. doi: 10.1016/j.autrev.2012.07.007.PubMedCrossRefGoogle Scholar
  92. 92.
    Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77(1):204–10.PubMedGoogle Scholar
  93. 93.
    Heaney RP. The Vitamin D requirement in health and disease. J Steroid Biochem Mol Biol. 2005;97(1-2):13–9. doi: 10.1016/j.jsbmb.2005.06.020.PubMedCrossRefGoogle Scholar
  94. 94.
    Vieth R. Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J Steroid Biochem Mol Biol. 2004;89/90(1/5):575–9. doi: 10.1016/j.jsbmb.2004.03.038.CrossRefGoogle Scholar
  95. 95.
    Kriegel MA, Manson JE, Costenbader KH. Does vitamin D affect risk of developing autoimmune disease? A systematic review. Semin Arthritis Rheum. 2011;40(6):512–531 e8. doi: 10.1016/j.semarthrit.2010.07.009.PubMedCrossRefGoogle Scholar
  96. 96.
    Gloth III FM, Tobin JD, Sherman SS, Hollis BW. Is the recommended daily allowance for vitamin D too low for the homebound elderly? J Am Geriatr Soc. 1991;39(2):137–41.PubMedCrossRefGoogle Scholar
  97. 97.
    Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res. 2003;18(2):343–51. doi: 10.1359/jbmr.2003.18.2.343.PubMedCrossRefGoogle Scholar
  98. 98.
    Vieth R, Cole DE, Hawker GA, Trang HM, Rubin LA. Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it. Eur J Clin Nutr. 2001;55(12):1091–7. doi: 10.1038/sj.ejcn.1601275.PubMedCrossRefGoogle Scholar
  99. 99.
    Munro I. Derivation of tolerable upper intake levels of nutrients. Am J Clin Nutr. 2001;74(6):865–7.PubMedGoogle Scholar
  100. 100.
    Vieth R. Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards. J Nutr. 2006;136(4):1117–22.PubMedGoogle Scholar
  101. 101.
    Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008;88(2):582S–6S.PubMedGoogle Scholar
  102. 102.
    Zittermann A, Prokop S, Gummert JF, Borgermann J. Safety issues of vitamin D supplementation. Anticancer Agents Med Chem. 2013;13(1):4–10.PubMedCrossRefGoogle Scholar
  103. 103.
    Lowe H, Cusano NE, Binkley N, Blaner WS, Bilezikian JP. Vitamin D toxicity due to a commonly available “over the counter” remedy from the Dominican Republic. J Clin Endocrinol Metab. 2011;96(2):291–5. doi: 10.1210/jc.2010-1999.PubMedCrossRefGoogle Scholar
  104. 104.
    Romagnoli E, Mascia ML, Cipriani C, Fassino V, Mazzei F, D’Erasmo E, et al. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008;93(8):3015–20. doi: 10.1210/jc.2008-0350.PubMedCrossRefGoogle Scholar
  105. 105.
    Heaney RP, Recker RR, Grote J, Horst RL, Armas LA. Vitamin D(3) is more potent than vitamin D(2) in humans. J Clin Endocrinol Metab. 2011;96(3):E447–52. doi: 10.1210/jc.2010-2230.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Barbara Altieri
    • 1
    Email author
  • Giovanna Muscogiuri
    • 2
  • Luigi Barrea
    • 2
  • Chantal Mathieu
    • 3
  • Carla V. Vallone
    • 4
  • Luca Mascitelli
    • 5
  • Giorgia Bizzaro
    • 6
  • Vincenzo M. Altieri
    • 7
  • Giacomo Tirabassi
    • 8
  • Giancarlo Balercia
    • 8
  • Silvia Savastano
    • 9
  • Nicola Bizzaro
    • 10
  • Cristina L. Ronchi
    • 11
  • Annamaria Colao
    • 9
  • Alfredo Pontecorvi
    • 1
  • Silvia Della Casa
    • 1
  1. 1.Division of Endocrinology and Metabolic Diseases, Institute of Medical PathologyCatholic University of the Sacred HeartRomeItaly
  2. 2.Ios and Coleman Medicina Futura Medical CenterUniversity Federico IINaplesItaly
  3. 3.Clinical and Experimental EndocrinologyKU LeuvenLeuvenBelgium
  4. 4.Emergency DepartmentFondazione Poliambulanza Istituto OspedalieroBresciaItaly
  5. 5.Comando Brigata Alpina Julia/Multinational Land Force, Medical ServiceUdineItaly
  6. 6.TSEM med Swiss SALuganoSwitzerland
  7. 7.Department of UrologyBolognini HospitalSeriateItaly
  8. 8.Division of Endocrinology, Department of Clinical and Molecular SciencesUmberto I Hospital, Polytechnic University of MarcheAnconaItaly
  9. 9.Department of Clinical Medicine and SurgeryUniversity “Federico II”NaplesItaly
  10. 10.Laboratory of Clinical PathologySan Antonio HospitalTolmezzoItaly
  11. 11.Division of Endocrinology and Diabetes, Department of Internal Medicine IUniversity Hospital of WuerzburgWuerzburgGermany

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