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.

  • Review
  • Published:

Vitamin D and thyroid disease: to D or not to D?

European Journal of Clinical Nutrition volume 69, pages 291–296 (2015)Cite this article

Subjects

Abstract

The main role of vitamin D is to maintain calcium and phosphorus homeostasis, thus preserving bone health. Recent evidence has demonstrated that vitamin D may also have a role in a variety of nonskeletal disorders such as endocrine diseases and in particular type 1 diabetes, type 2 diabetes, adrenal diseases and polycystic ovary syndrome. Low levels of vitamin D have also been associated with thyroid disease, such as Hashimoto’s thyroiditis. Similarly, patients with new-onset Graves’ disease were found to have decreased 25-hydroxyvitamin D concentrations. Impaired vitamin D signaling has been reported to encourage thyroid tumorigenesis. This review will focus on the role of vitamin D in thyroid diseases, both autoimmune diseases and thyroid cancer, and will summarize the results of vitamin D supplementation studies performed in patients with thyroid disorders. Although observational studies support a beneficial role of vitamin D in the management of thyroid disease, randomized controlled trials are required to provide insight into the efficacy and safety of vitamin D as a therapeutic tool for this dysfunction.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Basit S . Vitamin D in health and disease: a literature review. Br J Biomed Sci 2013; 70: 161–172.

    Article  CAS  PubMed  Google Scholar 

  2. Chapuy MC, Schott AM, Garnero P, Hans D, Delmas PD, Meunier PJ . Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter: EPIDOS Study Group. J Clin Endocrinol Metab 1996; 81: 1129–1133.

    CAS  PubMed  Google Scholar 

  3. Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G et al. The prevalence of vitamin D deficiency amongst women with osteoporosis: an international epidemiological investigation. J Intern Med 2006; 260: 245–254.

    Article  CAS  PubMed  Google Scholar 

  4. Holick MF . High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006; 81: 353–373.

    Article  CAS  PubMed  Google Scholar 

  5. Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ . Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med 2004; 158: 531–537.

    Article  PubMed  Google Scholar 

  6. Tangpricha V, Pearce EN, Chen TC, Holick MF . Vitamin D insufficiency among free-living healthy young adults. Am J Med 2002; 112: 659–662.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  Google Scholar 

  8. Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE et al. Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care 2013; 36: 1422–1428.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 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 2004; 151: 193–197.

    Article  CAS  PubMed  Google Scholar 

  10. Hahn S, Haselhorst U, Tan S, Quadbeck B, Schmidt M, Roesler S et al. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 2006; 114: 577–583.

    Article  CAS  PubMed  Google Scholar 

  11. McDonnell DP, Pike JW, O'Malley BW . The vitamin D receptor: a primitive steroid receptor related to thyroid hormone receptor. J Steroid Biochem 1988; 30: 41–46.

    Article  CAS  PubMed  Google Scholar 

  12. Lamberg-Allardt C, Valtonen E, Polojärvi M, Stewen P . Characterization of a 1,25-dihydroxy-vitamin D3 receptor in FRTL-5 cells. Evidence for an inhibitory effect of 1,25-dihydroxy-vitamin D3 on thyrotropin-induced iodide uptake. Mol Cell Endocrinol 1991; 81: 25–31.

    Article  CAS  PubMed  Google Scholar 

  13. Berg JP, Liane KM, Bjørhovde SB, Bjøro T, Torjesen PA, Haug E . Vitamin D receptor binding and biological effects of cholecalciferol analogues in rat thyroid cells. J Steroid Biochem Mol Biol 1994; 50: 145–150.

    Article  CAS  PubMed  Google Scholar 

  14. Törnquist K, Lamberg-Allardt C . Systemic effects of 1,25-dihydroxyvitamin D3 on the pituitary-hypothalamic axis in rats. Acta Endocrinol (Copenh) 1987; 115: 225–228.

    Article  Google Scholar 

  15. Tamer G, Arik S, Tamer I, Coksert D . Relative vitamin D insufficiency in Hashimoto’s thyroiditis. Thyroid 2011; 21: 891–896.

    Article  CAS  PubMed  Google Scholar 

  16. 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: 739–741.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Clinckspoor I, Verlinden L, Mathieu C, Bouillon R, Verstuyf A, Decallonne B . Vitamin D in thyroid tumorigenesis and development. Prog Histochem Cytochem 2013; 48: 65–98.

    Article  PubMed  Google Scholar 

  18. Baeke F, Etten EV, Overbergh L, Mathieu C . Vitamin D3 and the immune system: maintaining the balance in health and disease. Nutr Res Rev 2007; 20: 106–118.

    Article  CAS  PubMed  Google Scholar 

  19. Karthaus N, van Spriel AB, Looman MW, Chen S, Spilgies LM, Lieben L et al. Vitamin D controls murine and human plasmacytoid dendritic cell function. J Invest Dermatol 2014; 134: 1255–1264.

    Article  CAS  PubMed  Google Scholar 

  20. Mathieu C . Vitamin D and the immune system: getting it right. IBMS BoneKEy 2011; 8: 178–186.

    Article  Google Scholar 

  21. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C . Vitamin D: modulator of the immune system. Curr Opin Pharmacol 2010; 10: 482–496.

    Article  CAS  PubMed  Google Scholar 

  22. Inukai Y, Momobayashi A, Sugawara N, Aso Y . Changes in expression of T-helper (Th) 1- and Th2-associated chemokine receptors on peripheral blood lymphocytes and plasma concentrations of their ligands, interferon-inducible protein-10 and thymus and activation-regulated chemokine, after antithyroid drug administration in hyperthyroid patients with Graves' disease. Eur J Endocrinol 2007; 156: 623–630.

    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. Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Dankó K et al. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol 2011; 8: 243–247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Shin DY, Kim KJ, Kim D, Hwang S, Lee EJ . Low serum vitamin D is associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei Med J 2014; 55: 476–481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. 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 pre-menopausal women. Thyroid 2014; 24: 655–661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B . High vitamin D status in younger individuals is associated with low circulating thyrotropin. Thyroid 2013; 23: 25–30.

    Article  CAS  PubMed  Google Scholar 

  28. Goswami R, Marwaha RK, Gupta N, Tandon N, Sreenivas V, Tomar N et al. Prevalence of vitamin D deficiency and its relationships with thyroid autoimmunity in Asian Indians: a community-based survey. Br J Nutr 2009; 102: 382–386.

    Article  CAS  PubMed  Google Scholar 

  29. Effraimidis G, Badenhoop K, Tijssen JG, Wiersinga WM . Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur J Endocrinol 2012; 167: 43–48.

    Article  CAS  PubMed  Google Scholar 

  30. Mackawy AM, Al-Ayed BM, Al-Rashidi BM . Vitamin D deficiency and its association with thyroid disease. Int J Health Sci 2013; 7: 267–275.

    Article  Google Scholar 

  31. Zhang Q, Wang Z, Sun M, Cao M, Zhu Z, Fu Q et al. Association of high vitamin d status with low circulating thyroid-stimulating hormone independent of thyroid hormone levels in middle-aged and elderly males. Int J Endocrinol 2014; 2014: 631819.

    PubMed  PubMed Central  Google Scholar 

  32. Feng M, Li H, Chen SF, Li WF, Zhang FB . Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid disease: a meta-analysis. Endocrine 2013; 43: 318–326.

    Article  CAS  PubMed  Google Scholar 

  33. Pani MA, Regulla K, Segni M, Krause M, Hofmann S, Hufner M et al. Vitamin D 1α-hydroxylase (CYP1α) polymorphism in Graves’ disease, Hashimoto’s thyroiditis and type 1 diabetes mellitus. Eur J Endocrinol 2002; 146: 777–781.

    Article  CAS  PubMed  Google Scholar 

  34. Khadzkou K, Buchwald P, Westin G, Dralle H, Akerström G, Hellman P . 25-hydroxyvitamin D3 1alpha-hydroxylase and vitamin D receptor expression in papillary thyroid carcinoma. J Histochem Cytochem 2006; 54: 355–361.

    Article  CAS  PubMed  Google Scholar 

  35. Clinckspoor I, Hauben E, Verlinden L, Van den Bruel A, Vanwalleghem L, Vander Poorten V et al. Altered expression of key players in vitamin D metabolism and signaling in malignant and benign thyroid tumors. J Histochem Cytochem 2012; 60: 502–511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Somjen D, Grafi-Cohen M, Posner GH, Sharon O, Kraiem Z, Stern N . Vitamin D less-calcemic analog modulates the expression of estrogen receptors, vitamin D receptor and 1α-hydroxylase 25-hydroxy vitamin D in human thyroid cancer cell lines. J Steroid Biochem Mol Biol 2013; 136: 80–82.

    Article  CAS  PubMed  Google Scholar 

  37. Clinckspoor I, Verlinden L, Overbergh L, Korch C, Bouillon R, Mathieu C et al. 1,25-dihydroxyvitamin D3 and a superagonistic analog in combination with paclitaxel or suberoylanilide hydroxamic acid have potent antiproliferative effects on anaplastic thyroid cancer. J Steroid Biochem Mol Biol 2011; 124: 1–9.

    Article  CAS  PubMed  Google Scholar 

  38. Liu W, Asa SL, Fantus IG, Walfish PG, Ezzat S . Vitamin D arrests thyroid carcinoma cell growth and induces p27 dephosphorylation and accumulation through PTEN/akt-dependent and -independent pathways. Am J Pathol 2002; 160: 511–519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Suzuki S, Takenoshita S, Furukawa H, Tsuchiya A . Antineoplastic activity of 1,25(OH)2D3 and its analogue 22-oxacalcitriol against human anaplastic thyroid carcinoma cell lines in vitro. Int J Mol Med 1999; 4: 611–614.

    CAS  PubMed  Google Scholar 

  40. Bennett RG, Wakeley SE, Hamel FG, High RR, Korch C, Goldner WS . Gene expression of vitamin D metabolic enzymes at baseline and in response to vitamin D treatment in thyroid cancer cell lines. Oncology 2012; 83: 264–272.

    Article  CAS  PubMed  Google Scholar 

  41. Dackiw AP, Ezzat S, Huang P, Liu W, Asa SL . Vitamin D3 administration induces nuclear p27 accumulation, restores differentiation, and reduces tumor burden in a mouse model of metastatic follicular thyroid cancer. Endocrinology 2004; 145: 5840–5846.

    Article  CAS  PubMed  Google Scholar 

  42. Akagi T, Luong QT, Gui D, Said J, Selektar J, Yung A et al. Induction of sodium iodide symporter gene and molecular characterisation of HNF3 beta/FoxA2, TTF-1 and C/EBP beta in thyroid carcinoma cells. Br J Cancer 2008; 99: 781–788.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Peleg S, Abruzzese RV, Cooper CW, Gagel RF . Down-regulation of calcitonin gene transcription by vitamin D requires two widely separated enhancer sequences. Mol Endocrinol 1993; 7: 999–1008.

    CAS  PubMed  Google Scholar 

  44. Zabel M, Dietel M . Calcitriol decreases calcitonin secretion from a human medullary carcinoma cell line via specific receptor action. Acta Endocrinol (Copenh) 1991; 125: 299–304.

    Article  CAS  Google Scholar 

  45. Zabel M, Flig K, Gebarowska E, Surdyk-Zasada J . The effect of calcitriol and its analogues on proliferation and hormone expression in cultured cells of thyroid medullary carcinomas. Folia Morphol (Warsz) 2003; 62: 463–465.

    Google Scholar 

  46. Zabel M, Gebarowska E, Drag-Zalesińska M, Wysocka T . Effect of calcitriol on proliferation of TT cells and on expression of calcitonin gene. Folia Histochem Cytobiol 2002; 40: 187–188.

    CAS  PubMed  Google Scholar 

  47. Baier R, Grauer A, Lazaretti-Castro M, Ziegler R, Raue F . Differential effects of 1,25-dihydroxyvitamin D3 on cell proliferation and calcitonin gene expression. Endocrinology 1994; 135: 2006–2011.

    Article  CAS  PubMed  Google Scholar 

  48. Cote GJ, Rogers DG, Huang ES, Gagel RF . The effect of 1,25-dihydroxyvitamin D3 treatment on calcitonin and calcitonin gene-related peptide mRNA levels in cultured human thyroid C-cells. Biochem Biophys Res Commun 1987; 149: 239–243.

    Article  CAS  PubMed  Google Scholar 

  49. Liu W, Asa SL, Ezzat S . 1alpha,25-Dihydroxyvitamin D3 targets PTEN-dependent fibronectin expression to restore thyroid cancer cell adhesiveness. Mol Endocrinol 2005; 19: 2349–2357.

    Article  CAS  PubMed  Google Scholar 

  50. Roskies M, Dolev Y, Caglar D, Hier MP, Mlynarek A, Majdan A et al. Vitamin D deficiency as a potentially modifiable risk factor for thyroid cancer. J Otolaryngol Head Neck Surg 2012; 41: 160–163.

    PubMed  Google Scholar 

  51. Sahin M, Uçan B, Giniş Z, Topaloğlu O, Güngüneş A, Bozkurt NÇ et al. Vitamin D3 levels and insulin resistance in papillary thyroid cancer patients. Med Oncol 2013; 30: 589.

    Article  PubMed  Google Scholar 

  52. Stepien T, Krupinski R, Sopinski J, Kuzdak K, Komorowski J, Lawnicka H et al. Decreased 1–25 dihydroxyvitamin D3 concentration in peripheral blood serum of patients with thyroid cancer. Arch Med Res 2010; 41: 190–194.

    Article  CAS  PubMed  Google Scholar 

  53. Jonklaas J, Danielsen M, Wang H . A pilot study of serum selenium, vitamin D, and thyrotropin concentrations in patients with thyroid cancer. Thyroid 2013; 23: 1079–1086.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Laney N, Meza J, Lyden E, Erickson J, Treude K, Goldner W . The prevalence of vitamin D deficiency is similar between thyroid nodule and thyroid cancer patients. Int J Endocrinol 2010; 2010: 805716.

    Article  PubMed  Google Scholar 

  55. Mack WJ, Preston-Martin S, Bernstein L, Qian D . Lifestyle and other risk factors for thyroid cancer in Los Angeles County females. Ann Epidemiol 2002; 12: 395–401.

    Article  PubMed  Google Scholar 

  56. Ron E, Kleinerman RA, Boice Jr JD, LiVolsi VA, Flannery JT, Fraumeni Jr JF . A population-based case-control study of thyroid cancer. J Natl Cancer Inst 1987; 79: 1–12.

    CAS  PubMed  Google Scholar 

  57. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP et al. Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96: 1911–1930.

    Article  CAS  PubMed  Google Scholar 

  58. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and CalciumIn: Ross AC, Taylor CL, Yaktine AL, Del Valle HB (eds). Dietary Reference Intakes for Calcium and Vitamin D. National Academies Press (US): Washington (DC), 2011.

  59. Agmon-Levin N, Theodor E, Segal RM, Shoenfeld Y . Vitamin D in systemic and organ-specific autoimmune diseases. Clin Rev Allergy Immunol 2013; 45: 256–266.

    Article  CAS  PubMed  Google Scholar 

  60. Fournier C, Gepner P, Sadouk M, Charreire J . In vivo beneficial effects of cyclosporin A and 1,25-dihydroxyvitamin D3 on the induction of experimental autoimmune thyroiditis. Clin Immunol Immunopathol 1990; 54: 53–63.

    Article  CAS  PubMed  Google Scholar 

  61. 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.

    Article  CAS  PubMed  Google Scholar 

  62. Robien K, Oppeneer SJ, Kelly JA, Hamilton-Reeves JM . Drug-vitamin D interactions: a systematic review of the literature. Nutr Clin Pract 2013; 28: 194–208.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Brannon PM, Yetley EA, Bailey RL, Picciano MF . Summary of roundtable discussion on vitamin D research needs. Am J Clin Nutr 2008; 88: 587–592.

    Article  Google Scholar 

  64. Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med 2013; 369: 1991–2000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Hollis BW . Comparison of commercially available (125)I-based RIA methods for the determination of circulating 25-hydroxyvitamin D. Clin Chem 2000; 46: 1657–1661.

    CAS  PubMed  Google Scholar 

  66. Gilbertson TJ, Stryd RP . High-performance liquid chromatographic assay for 25-hydroxyvitamin D3 in serum. Clin Chem 1977; 23: 1700–1704.

    CAS  PubMed  Google Scholar 

  67. Saenger AK, Laha TJ, Bremner DE, Sadrzadeh SM . Quantification of serum 25-hydroxyvitamin D(2) and D(3) using HPLC-tandem mass spectrometry and examination of reference intervals for diagnosis of vitamin D deficiency. Am J Clin Pathol 2006; 125: 914–920.

    Article  CAS  PubMed  Google Scholar 

  68. Tsugawa N, Suhara Y, Kamao M, Okano T . Determination of 25-hydroxyvitamin D in human plasma using high-performance liquid chromatography—tandem mass spectrometry. Anal Chem 2005; 77: 3001–3007.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Medicine and Surgery, Section of Endocrinology, University ‘Federico II’, Naples, Italy

    G Muscogiuri & A Colao

  2. Division of Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, School of Medicine, Polytechnic University of Marche, Ancona, Italy

    G Tirabassi & G Balercia

  3. The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel

    G Bizzaro & Y Shoenfeld

  4. Department of General Surgery and Transplantation Unit ‘San Giovanni di Dio e Ruggi D’Aragona’ University Hospital, Scuola Medica Salernitana, Salerno, Italy

    F Orio

  5. Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital, Athens, Greece

    S A Paschou & A Vryonidou

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

    Y Shoenfeld

Authors
  1. G Muscogiuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G Tirabassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Bizzaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F Orio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S A Paschou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Vryonidou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G Balercia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Y Shoenfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Colao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G Muscogiuri.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Disclaimer

No external funding, apart from the support of the authors' institution, was available for this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Muscogiuri, G., Tirabassi, G., Bizzaro, G. et al. Vitamin D and thyroid disease: to D or not to D?. Eur J Clin Nutr 69, 291–296 (2015). https://doi.org/10.1038/ejcn.2014.265

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2014.265

This article is cited by

Search

Advanced search

Quick links