Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Vitamin D and autoimmune thyroid diseases

Cellular & Molecular Immunology volume 8, pages 243–247 (2011)Cite this article

Abstract

The role of vitamin D as an immune modulator has been emphasized in recent years, and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemic lupus erythematosus. Vitamin D mediates its effect though binding to vitamin D receptor (VDR), and activation of VDR-responsive genes. While VDR gene polymorphism was found to associate with autoimmune thyroid diseases (AITDs), few studies examined levels of vitamin D in these patients and those that did yielded conflicting results. We therefore undertook to evaluate the levels of vitamin D in patients with AITDs compared to patients with non-AITDs and healthy controls. Serum vitamin D (25-OH) levels were measured in 50 patients with AITDs, 42 patients with non-AITDs and 98 healthy subjects, utilizing the LIAISON chemiluminescence immunoassay (DiaSorin, Saluggia, Italy). Vitamin D deficiency was designated at levels lower than 10 ng/ml. Antithyroid antibodies, thyroid functions and demographic parameters were evaluated in all patients. The prevalence of vitamin D deficiency was significantly higher in patients with AITDs compared with healthy individuals (72% versus 30.6%; P<0.001), as well as in patients with Hashimoto's thyroiditis compared to patients with non-AITDs (79% versus 52%; P<0.05). Vitamin D deficiency also correlated to the presence of antithyroid antibodies (P=0.01) and abnormal thyroid function tests (P=0.059). Significantly low levels of vitamin D were documented in patients with AITDs that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests, suggesting the involvement of vitamin D in the pathogenesis of AITDs and the advisability of supplementation.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Zittermann A, Schleithoff SS, Koerfer R . Putting cardiovascular disease and vitamin D insufficiency into perspective. Br J Nutr 2005; 94: 483–492.

    Article  CAS  PubMed  Google Scholar 

  2. Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 2006; 98: 451–459.

    Article  CAS  PubMed  Google Scholar 

  3. Shapira Y, Agmon-Levin N, Shoenfeld Y . Mycobacterium tuberculosis, autoimmunity, and vitamin D. Clin Rev Allergy Immunol 2009; 39: 3147–3159.

    Google Scholar 

  4. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008; 117: 503–511.

    Article  CAS  PubMed  Google Scholar 

  5. Giovannucci E . Epidemiological evidence for vitamin D and colorectal cancer. J Bone Miner Res 2007; 22 Suppl 2: V81–V85.

    Article  CAS  PubMed  Google Scholar 

  6. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM . Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001; 358: 1500–1503.

    Article  CAS  PubMed  Google Scholar 

  7. Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG . Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study. Arthritis Rheum 2004; 50: 72–77.

    Article  CAS  PubMed  Google Scholar 

  8. Huisman AM, White KP, Algra A, Harth M, Vieth R, Jacobs JW et al. Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia. J Rheumatol 2001; 28: 2535–2539.

    CAS  PubMed  Google Scholar 

  9. Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS . Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev 2006; 5: 114–117.

    Article  CAS  PubMed  Google Scholar 

  10. Ben-Zvi I, Aranow C, Mackay M, Stanevsky A, Kamen DL, Marinescu LM et al. The impact of vitamin D on dendritic cell function in patients with systemic lupus erythematosus. PLoS One 2010; 5: e9193.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Shapira Y, Agmon-Levin N, Shoenfeld Y . Geoepidemiology of autoimmune diseases. Autoimmunity 2010; 8: 468–476.

    Google Scholar 

  12. Shoenfeld N, Amital H, Shoenfeld Y . The effect of melanism and vitamin D synthesis on the incidence of autoimmune disease. Nat Clin Pract Rheumatol 2009; 5: 99–105

    Article  CAS  PubMed  Google Scholar 

  13. Ascherio A, Munger KL . Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann Neurol 2007; 61: 504–513.

    Article  CAS  PubMed  Google Scholar 

  14. Dahlquist G, Mustonen L . Childhood onset diabetes—time trends and climatological factors. Int J Epidemiol 1994; 23: 1234–1241.

    Article  CAS  PubMed  Google Scholar 

  15. The EURODIAB Substudy 2 Study Group. Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. Diabetologia 1999; 42: 51–54.

    Article  Google Scholar 

  16. Mathieu C, Laureys J, Sobis H, Vandeputte M, Waer M, Bouillon R . 1,25-Dihydroxyvitamin D3 prevents insulitis in NOD mice. Diabetes 1992; 41: 1491–1495.

    Article  CAS  PubMed  Google Scholar 

  17. Andjelkovic Z, Vojinovic J, Pejnovic N, Popovic M, Dujic A, Mitrovic D et al. Disease modifying and immunomodulatory effects of high dose 1 alpha (OH) D3 in rheumatoid arthritis patients. Clin Exp Rheumatol 1999; 17: 453–456.

    CAS  PubMed  Google Scholar 

  18. Myhr KM . Vitamin D treatment in multiple sclerosis. J Neurol Sci 2009; 286: 104–108.

    Article  CAS  PubMed  Google Scholar 

  19. Munger KL, Zhang SM, O'Reilly E, Hernán MA, Olek MJ, Willett WC et al. Vitamin D intake and incidence of multiple sclerosis. Neurology 2004; 62: 60–65.

    Article  CAS  PubMed  Google Scholar 

  20. Huckins D, Felson DT, Holick M . Treatment of psoriatic arthritis with oral 1,25-dihydroxyvitamin D3: a pilot study. Arthritis Rheum 1990; 33: 1723–1727.

    Article  CAS  PubMed  Google Scholar 

  21. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A . Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006; 296: 2832–2838.

    Article  CAS  PubMed  Google Scholar 

  22. Chen W, Lin H, Wang M . Immune intervention effects on the induction of experimental autoimmune thyroiditis. J Huazhong Univ Sci Technolog Med Sci 2002; 22: 343–345, 354.

    Article  CAS  PubMed  Google Scholar 

  23. Misharin A, Hewison M, Chen CR, Lagishetty V, Aliesky HA, Mizutori Y et al. Vitamin D deficiency modulates Graves' hyperthyroidism induced in BALB/c mice by thyrotropin receptor immunization. Endocrinology 2009; 150: 1051–1060.

    Article  CAS  PubMed  Google Scholar 

  24. Orbach H, Shoenfeld Y . Vaccination infection and autoimmunity: myth and reality VIAMR 2005-10-26-28, Beau-Rivage Palace Hotel, Lausanne, Switzerland. Autoimmun Rev 2007; 6: 261–266.

    Article  CAS  PubMed  Google Scholar 

  25. Czernobilsky H, Scharla S, Schmidt-Gayk H, Ziegler R . Enhanced suppression of 1,25(OH)2D3 and intact parathyroid hormone in Graves' disease as compared to toxic nodular goiter. Calcif Tissue Int 1988; 42: 5–12.

    Article  CAS  PubMed  Google Scholar 

  26. 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: 382–386.

    Article  CAS  PubMed  Google Scholar 

  27. Shoenfeld Y, Selmi C, Zimlichman E, Gershwin ME . The autoimmunologist: geoepidemiology, a new center of gravity, and prime time for autoimmunity. J Autoimmun 2008; 31: 325–330.

    Article  PubMed  Google Scholar 

  28. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC . The Colorado thyroid disease prevalence study. Arch Intern Med 2000; 160: 526–534.

    Article  CAS  PubMed  Google Scholar 

  29. Shoenfeld Y, Blank M, Abu-Shakra M, Amital H, Barzilai O, Berkun Y et al. The mosaic of autoimmunity: prediction, autoantibodies, and therapy in autoimmune diseases—2008. Isr Med Assoc J 2008; 10: 13–19.

    PubMed  Google Scholar 

  30. Shoenfeld Y, Gilburd B, Abu-Shakra M, Amital H, Barzilai O, Berkun Y et al. The mosaic of autoimmunity: genetic factors involved in autoimmune diseases—2008. Isr Med Assoc J 2008; 10: 3–7.

    PubMed  Google Scholar 

  31. Shoenfeld Y, Zandman-Goddard G, Stojanovich L, Cutolo M, Amital H, Levy Y et al. The mosaic of autoimmunity: hormonal and environmental factors involved in autoimmune diseases—2008. Isr Med Assoc J 2008; 10: 8–12.

    PubMed  Google Scholar 

  32. Tozzoli R, Barzilai O, Ram M, Villalta D, Bizzaro N, Sherer Y et al. Infections and autoimmune thyroid diseases: parallel detection of antibodies against pathogens with proteomic technology. Autoimmun Rev 2008; 8: 112–115.

    Article  CAS  PubMed  Google Scholar 

  33. Gershwin ME . The mosaic of autoimmunity. Autoimmun Rev 2008; 7: 161–163.

    Article  PubMed  Google Scholar 

  34. van Etten E, Mathieu C . Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol 2005; 97: 93–101.

    Article  CAS  PubMed  Google Scholar 

  35. Arnson Y, Amital H, Shoenfeld Y . Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis 2007; 66: 1137–1142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res 1998; 13: 325–349.

    Article  CAS  PubMed  Google Scholar 

  37. Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG . Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab 1986; 63: 954–959.

    Article  CAS  PubMed  Google Scholar 

  38. Henry HL . Vitamin D hydroxylases. J Cell Biochem 1992; 49: 4–9.

    Article  CAS  PubMed  Google Scholar 

  39. Penna G, Adorini L . 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 2000; 164: 2405–2411.

    Article  CAS  PubMed  Google Scholar 

  40. van Halteren AG, van Etten E, de Jong EC, Bouillon R, Roep BO, Mathieu C . Redirection of human autoreactive T-cells upon interaction with dendritic cells modulated by TX527, an analog of 1,25 dihydroxyvitamin D3. Diabetes 2002; 51: 2119–2125.

    Article  CAS  PubMed  Google Scholar 

  41. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O'Garra A . 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4+ T cells to enhance the development of Th2 cells. J Immunol 2001; 167: 4974–4980.

    Article  CAS  PubMed  Google Scholar 

  42. Lagunova Z, Porojnicu AC, Lindberg F, Hexeberg S, Moan J . The dependency of vitamin D status on body mass index, gender, age and season. Anticancer Res 2009; 29: 3713–3720.

    CAS  PubMed  Google Scholar 

  43. Gomez-Alonso C, Naves-Diaz ML, Fernandez-Martin JL, Diaz-Lopez JB, Fernandez-Coto MT, Cannata-Andia JB . Vitamin D status and secondary hyperparathyroidism: the importance of 25-hydroxyvitamin D cut-off levels. Kidney Int Suppl 2003; (85): S44–S48.

    Article  Google Scholar 

  44. Iqbal AA, Burgess EH, Gallina DL, Nanes MS, Cook CB . Hypercalcemia in hyperthyroidism: patterns of serum calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis. Endocr Pract 2003; 9: 517–521.

    Article  PubMed  Google Scholar 

  45. Pani MA, Knapp M, Donner H, Braun J, Baur MP, Usadel KH et al. Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans. Diabetes 2000; 49: 504–507.

    Article  CAS  PubMed  Google Scholar 

  46. Pani MA, Seissler J, Usadel KH, Badenhoop K . Vitamin D receptor genotype is associated with Addison's disease. Eur J Endocrinol 2002; 147: 635–640.

    Article  CAS  PubMed  Google Scholar 

  47. Horst-Sikorska W, Ignaszak-Szczepaniak M, Marcinkowska M, Kaczmarek M, Stajgis M, Slomski R . Association analysis of vitamin D receptor gene polymorphisms with bone mineral density in young women with Graves' disease. Acta Biochim Pol 2008; 55: 371–380.

    CAS  PubMed  Google Scholar 

  48. Stefanic M, Papic S, Suver M, Glavas-Obrovac L, Karner I . Association of vitamin D receptor gene 3′-variants with Hashimoto's thyroiditis in the Croatian population. Int J Immunogenet 2008; 35: 125–131.

    Article  CAS  PubMed  Google Scholar 

  49. Kurylowicz A, Ramos-Lopez E, Bednarczuk T, Badenhoop K . Vitamin D-binding protein (DBP) gene polymorphism is associated with Graves' disease and the vitamin D status in a Polish population study. Exp Clin Endocrinol Diabetes 2006; 114: 329–335.

    Article  CAS  PubMed  Google Scholar 

  50. Ban Y, Ban Y, Taniyama M, Katagiri T . Vitamin D receptor initiation codon polymorphism in Japanese patients with Graves' disease. Thyroid 2000; 10: 475–480.

    Article  CAS  PubMed  Google Scholar 

  51. Miller AE, Morgante LA, Buchwald LY, Nutile SM, Coyle PK, Krupp LB et al. A multicenter, randomized, double-blind, placebo-controlled trial of influenza immunization in multiple sclerosis. Neurology 1997; 48: 312–314.

    Article  CAS  PubMed  Google Scholar 

  52. Collins JE, Heward JM, Nithiyananthan R, Nejentsev S, Todd JA, Franklyn JA et al. Lack of association of the vitamin D receptor gene with Graves' disease in UK Caucasians. Clin Endocrinol (Oxf) 2004; 60: 618–624.

    Article  CAS  Google Scholar 

  53. von Restorff C, Bischoff-Ferrari HA, Theiler R . High-dose oral vitamin D3 supplementation in rheumatology patients with severe vitamin D3 deficiency. Bone 2009; 45: 747–749.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Shaye Kivity and Nancy Agmon-Levin: *These authors contributed equally to this work.

Authors and Affiliations

  1. The Zabludovicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Shaye Kivity, Nancy Agmon-Levin, Michael Zisappl, Yinon Shapira & Yehuda Shoenfeld

  2. Department of Medicine ‘A & C’, Sheba Medical Center, Tel-Hashomer, Israel

    Shaye Kivity

  3. Rheumatic Disease Unit, Sheba Medical Center, Tel-Hashomer, Israel

    Shaye Kivity & Pnina Langevitz

  4. Department of Medicine ‘B’, Sheba Medical Center, Tel-Hashomer, Israel

    Nancy Agmon-Levin & Yehuda Shoenfeld

  5. University of Debrecen. Medical and Health Science Center, Debrecen, Hungary

    Endre V Nagy, Katalin Dankó & Zoltan Szekanecz

  6. Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune Diseases, Tel Aviv University, Tel Aviv, Israel

    Yehuda Shoenfeld

Authors
  1. Shaye Kivity
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nancy Agmon-Levin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Zisappl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yinon Shapira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Endre V Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Katalin Dankó
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zoltan Szekanecz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pnina Langevitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yehuda Shoenfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yehuda Shoenfeld.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kivity, S., Agmon-Levin, N., Zisappl, M. et al. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol 8, 243–247 (2011). https://doi.org/10.1038/cmi.2010.73

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2010.73

Keywords

  • autoantibodies
  • autoimmune thyroid disease
  • Graves' disease
  • Hashimoto's thyroiditis
  • vitamin D

This article is cited by

Search

Advanced search

Quick links