The Role of Vitamin D in Thyroid Diseases
Abstract
:1. Introduction
2. Vitamin D Sources, Metabolism, and Action
3. Vitamin D and Autoimmune Thyroid Diseases
3.1. Mechanisms
3.2. Animal Studies
3.3. Human Studies
4. Vitamin D and Thyroid Cancers
4.1. Mechanisms
4.2. In Vitro and Animal Studies
4.3. Human Studies
5. Limitations in the Study of Vitamin D
6. Conclusions
Conflicts of Interest
References
- Makariou, S.; Liberopoulos, E.N.; Elisaf, M.; Challa, A. Novel roles of vitamin D in disease: What is new in 2011? Eur. J. Intern. Med. 2011, 22, 355–362. [Google Scholar] [CrossRef] [PubMed]
- Holick, M.F. Vitamin D deficiency. N. Engl. J. Med. 2007, 357, 266–281. [Google Scholar] [CrossRef] [PubMed]
- Plum, L.A.; DeLuca, H.F. Vitamin D, disease and therapeutic opportunities. Nat. Rev. Drug Discov. 2010, 9, 941–955. [Google Scholar] [CrossRef] [PubMed]
- Muscogiuri, G.; Tirabassi, G.; Bizzaro, G.; Orio, F.; Paschou, S.A.; Vryonidou, A.; Balercia, G.; Shoenfeld, Y.; Colao, A. Vitamin D and thyroid disease: To D or not to D? Eur. J. Clin. Nutr. 2015, 69, 291–296. [Google Scholar] [CrossRef] [PubMed]
- Kmieć, P.; Sworczak, K. Vitamin D in thyroid disorders. Exp. Clin. Endocrinol. Diabetes 2015, 123, 386–393. [Google Scholar] [CrossRef] [PubMed]
- Vondra, K.; Stárka, L.; Hampl, R. Vitamin D and thyroid diseases. Physiol. Res. 2015, 64, S95–S100. [Google Scholar] [PubMed]
- Bikle, D. Nonclassic actions of vitamin D. J. Clin. Endocrinol. Metab. 2009, 94, 26–34. [Google Scholar] [CrossRef] [PubMed]
- Prietl, B.; Treiber, G.; Pieber, T.R.; Amrein, K. Vitamin D and immune function. Nutrients 2013, 5, 2502–2521. [Google Scholar] [CrossRef] [PubMed]
- Wacker, M.; Holick, M.F. Vitamin D—Effects on skeletal and extraskeletal health and the need for supplementation. Nutrients 2013, 5, 111–148. [Google Scholar] [CrossRef] [PubMed]
- Holick, M.F.; Binkley, N.C.; Bischoff-Ferrari, H.A.; Gordon, C.M.; Hanley, D.A.; Heaney, R.P.; Murad, M.H.; Weaver, C.M. Evaluation, treatment, and prevention of vitamin D deficiency: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 2011, 96, 1911–1930. [Google Scholar] [CrossRef] [PubMed]
- 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, 14, 363–369. [Google Scholar] [CrossRef] [PubMed]
- Klecha, A.J.; Barreiro Arcos, M.L.; Frick, L.; Genaro, A.M.; Cremaschi, G. Immune-endocrine interactions in autoimmune thyroid diseases. Neuroimmunomodulation 2008, 15, 68–75. [Google Scholar] [CrossRef] [PubMed]
- Fountoulakis, S.; Tsatsoulis, A. On the pathogenesis of autoimmune thyroid disease: A unifying hypothesis. Clin. Endocrinol. 2004, 60, 397–409. [Google Scholar] [CrossRef] [PubMed]
- Baeke, F.; Takiishi, T.; Korf, H.; Gysemans, C.; Mathieu, C. Vitamin D: Modulator of the immune system. Curr. Opin. Pharmacol. 2010, 10, 482–496. [Google Scholar] [CrossRef] [PubMed]
- Mathieu, C.; Adorini, L. The coming of age of 1,25-dihydroxyvitamin D3 analogs as immunomodulatory agents. Trends Mol. Med. 2002, 8, 174–179. [Google Scholar] [CrossRef]
- Hewison, M. An update on vitamin D and human immunity. Clin. Endocrinol. 2012, 76, 315–325. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef]
- Chen, W.; Lin, H.; Wang, M. Immune intervention effects on the induction of experimental autoimmune thyroiditis. J. Huazhong Univ. Sci. Technol. Med. Sci. 2002, 22, 343–345. [Google Scholar] [CrossRef] [PubMed]
- Liu, S.; Xiong, F.; Liu, E.M.; Zhu, M.; Lei, P.Y. Effects of 1,25-dihydroxyvitamin D3 in rats with experimental autoimmune thyroiditis. J. South. Med. Univ. 2010, 30, 1573–1576. [Google Scholar]
- Misharin, A.; Hewison, M.; Chen, C.R.; Lagishetty, V.; Aliesky, H.A.; Mizutori, Y.; Rapoport, B.; McLachlan, S.M. Vitamin D deficiency modulates Graves’ hyperthyroidism induced in BALB/c mice by thyrotropin receptor immunization. Endocrinology 2009, 50, 1051–1060. [Google Scholar] [CrossRef] [PubMed]
- Kivity, S.; Agmon-Levin, N.; Zisappl, M.; Shapira, Y.; Nagy, E.V.; Dankó, K.; Szekanecz, Z.; Langevitz, P.; Shoenfeld, Y. Vitamin D and autoimmune thyroid diseases. Cell. Mol. Immunol. 2011, 8, 243–247. [Google Scholar] [CrossRef] [PubMed]
- Tamer, G.; Arik, S.; Tamer, I.; Coksert, D. Relative vitamin D insufficiency in Hashimoto’s thyroiditis. Thyroid 2011, 21, 891–896. [Google Scholar] [CrossRef] [PubMed]
- Bozkurt, N.C.; Karbek, B.; Ucan, B.; Sahin, M.; Cakal, E.; Ozbek, M.; Delibasi, T. The association between severity of vitamin D deficiency and Hashimoto’s thyroiditis. Endocr. Pract. 2013, 19, 479–484. [Google Scholar] [CrossRef] [PubMed]
- Mansournia, N.; Mansournia, M.A.; Saeedi, S.; Dehghan, J. The association between serum 25OHD levels and hypothyroid Hashimoto’s thyroiditis. J. Endocrinol. Investig. 2014, 37, 473–476. [Google Scholar] [CrossRef] [PubMed]
- Shin, D.Y.; Kim, K.J.; Kim, D.; Hwang, S.; Lee, E.J. Low serum vitamin D is associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei Med. J. 2014, 55, 476–481. [Google Scholar] [CrossRef] [PubMed]
- Unal, A.D.; Tarcin, O.; Parildar, H.; Cigerli, O.; Eroglu, H.; Demirag, N.G. Vitamin D deficiency is related to thyroid antibodies in autoimmune thyroiditis. Cent. Eur. J. Immunol. 2014, 39, 493–497. [Google Scholar] [CrossRef] [PubMed]
- Choi, Y.M.; Kim, W.G.; Kim, T.Y.; Bae, S.J.; Kim, H.K.; Jang, E.K.; Jeon, M.J.; Han, J.M.; Lee, S.H.; Baek, J.H.; et al. Low levels of serum vitamin D3 are associated with autoimmune thyroid disease in pre-menopausal women. Thyroid 2014, 24, 655–661. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Zynat, J.; Guo, Y.; Osiman, R.; Tuhuti, A.; Zhao, H.; Abdunaimu, M.; Wang, H.; Jin, X.; Xing, S. Low serum vitamin D is associated with anti-thyroid-globulin antibody in female individuals. Int. J. Endocrinol. 2015, 2015, 285290. [Google Scholar] [CrossRef] [PubMed]
- Kim, D. Low vitamin D status is associated with hypothyroid Hashimoto’s thyroiditis. Hormones 2016, 15, 385–393. [Google Scholar] [CrossRef] [PubMed]
- 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, 7, 2485–2498. [Google Scholar] [CrossRef] [PubMed]
- Muscogiuri, G.; Mari, D.; Prolo, S.; Fatti, L.M.; Cantone, M.C.; Garagnani, P.; Arosio, B.; Di Somma, C.; Vitale, G. 25 Hydroxyvitamin D deficiency and its relationship to autoimmune thyroid disease in the elderly. Int. J. Environ. Res. Public Health 2016, 13, E850. [Google Scholar] [CrossRef] [PubMed]
- Camurdan, OM.; Döğer, E.; Bideci, A.; Celik, N.; Cinaz, P. Vitamin D status in children with Hashimoto thyroiditis. J. Pediatr. Endocrinol. Metab. 2012, 25, 467–470. [Google Scholar] [CrossRef] [PubMed]
- Evliyaoğlu, O.; Acar, M.; Özcabı, B.; Erginöz, E.; Bucak, F.; Ercan, O.; Kucur, M. Vitamin D deficiency and Hashimoto’s thyroiditis in children and adolescents: A critical vitamin D level for this association? J. Clin. Res. Pediatr. Endocrinol. 2015, 7, 128–133. [Google Scholar] [CrossRef] [PubMed]
- Metwalley, K.A.; Farghaly, H.S.; Sherief, T.; Hussein, A. Vitamin D status in children and adolescents with autoimmune thyroiditis. J. Endocrinol. Investig. 2016, 39, 793–797. [Google Scholar] [CrossRef] [PubMed]
- Goswami, R.; Marwaha, R.K.; Gupta, N.; Tandon, N.; Sreenivas, V.; Tomar, N.; Ray, D.; Kanwar, R.; Agarwal, R. 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. [Google Scholar] [CrossRef] [PubMed]
- Effraimidis, G.; Badenhoop, K.; Tijssen, J.G.; Wiersinga, W.M. Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur. J. Endocrinol. 2012, 167, 43–48. [Google Scholar] [CrossRef] [PubMed]
- Yasmeh, J.; Farpour, F.; Rizzo, V.; Kheradnam, S.; Sachmechi, I. Hashimoto thyroiditis not associated with vitamin D deficiency. Endocr. Pract. 2016, 22, 809–813. [Google Scholar] [CrossRef] [PubMed]
- Yasuda, T.; Okamoto, Y.; Hamada, N.; Miyashita, K.; Takahara, M.; Sakamoto, F.; Miyatsuka, T.; Kitamura, T.; Katakami, N.; Kawamori, D.; 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. [Google Scholar] [CrossRef] [PubMed]
- Yasuda, T.; Okamoto, Y.; Hamada, N.; Miyashita, K.; Takahara, M.; Sakamoto, F.; Miyatsuka, T.; Kitamura, T.; Katakami, N.; Kawamori, D.; et al. Serum vitamin D levels are decreased in patients without remission of Graves’ disease. Endocrine 2013, 43, 230–232. [Google Scholar] [CrossRef] [PubMed]
- Zhang, H.; Liang, L.; Xie, Z. Low vitamin D status is associated with increased thyrotropin-receptor antibody titer in Graves’ disease. Endocr. Pract. 2015, 21, 258–263. [Google Scholar] [CrossRef] [PubMed]
- Mazokopakis, E.E.; Papadomanolaki, M.G.; Tsekouras, K.C.; Evangelopoulos, A.D.; Kotsiris, D.A.; Tzortzinis, A.A. Is vitamin D related to pathogenesis and treatment of Hashimoto’s thyroiditis? Hell. J. Nucl. Med. 2015, 18, 222–227. [Google Scholar] [PubMed]
- Chaudhary, S.; Dutta, D.; Kumar, M.; Saha, S.; Mondal, S.A.; 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, 20, 391–398. [Google Scholar] [CrossRef] [PubMed]
- Simsek, Y.; Cakır, I.; Yetmis, M.; Dizdar, O.S.; Baspinar, O.; Gokay, F. Effects of Vitamin D treatment on thyroid autoimmunity. J. Res. Med. Sci. 2016, 21, 85. [Google Scholar] [CrossRef] [PubMed]
- 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, 7, 3813–3827. [Google Scholar] [CrossRef] [PubMed]
- Zhou, H.; Xu, C.; Gu, M. Vitamin D receptor (VDR) gene polymorphisms and Graves’ disease: A meta-analysis. Clin. Endocrinol. 2009, 70, 938–945. [Google Scholar] [CrossRef] [PubMed]
- Feng, M.; Li, H.; Chen, S.F.; Li, W.F.; Zhang, F.B. Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: A meta-analysis. Endocrine 2013, 43, 318–326. [Google Scholar] [CrossRef] [PubMed]
- Inoue, N.; Watanabe, M.; Ishido, N.; Katsumata, Y.; Kagawa, T.; Hidaka, Y.; Iwatani, Y. The functional polymorphisms of VDR, GC and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases. Clin. Exp. Immunol. 2014, 178, 262–269. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Cheng, W.; Ma, Y.; Zhu, J. Vitamin D receptor gene FokI but not TaqI, ApaI, BsmI polymorphism is associated with Hashimoto’s thyroiditis: A meta-analysis. Sci. Rep. 2017, 7, 41540. [Google Scholar] [CrossRef] [PubMed]
- Pani, M.A.; Regulla, K.; Segni, M.; Hofmann, S.; Hüfner, M.; Pasquino, A.M.; Usadel, K.H.; Badenhoop, K. A polymorphism within the vitamin D-binding protein gene is associated with Graves’ disease but not with Hashimoto’s thyroiditis. J. Clin. Endocrinol. Metab. 2002, 87, 2564–2567. [Google Scholar] [PubMed]
- Pani, M.A.; Regulla, K.; Segni, M.; Krause, M.; Hofmann, S.; Hufner, M.; Herwig, J.; Pasquino, A.M.; Usadel, K.H.; Badenhoop, K. Vitamin D 1alpha-hydroxylase (CYP1alpha) polymorphism in Graves’ disease, Hashimoto’s thyroiditis and type 1 diabetes mellitus. Eur. J. Endocrinol. 2002, 146, 777–781. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- Feldman, D.; Krishnan, A.V.; Swami, S.; Giovannucci, E.; Feldman, B.J. The role of vitamin D in reducing cancer risk and progression. Nat. Rev. Cancer 2014, 14, 342–357. [Google Scholar] [CrossRef] [PubMed]
- Díaz, L.; Díaz-Muñoz, M.; García-Gaytán, A.C.; Méndez, I. Mechanistic effects of calcitriol in cancer biology. Nutrients 2015, 7, 5020–5050. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- Morand, G.B.; da Silva, S.D.; Hier, M.P.; Alaoui-Jamali, M.A. Insights into genetic and epigenetic determinants with impact on vitamin D signaling and cancer association studies: The case of thyroid cancer. Front. Oncol. 2014, 4, 309. [Google Scholar] [CrossRef] [PubMed]
- Chiang, K.C.; Kuo, S.F.; Chen, C.H.; Ng, S.; Lin, S.F.; Yeh, C.N.; Chen, L.W.; Takano, M.; Chen, T.C.; Juang, H.H.; et al. MART-10, the vitamin D analog, is a potent drug to inhibit anaplastic thyroid cancer cell metastatic potential. Cancer Lett. 2015, 369, 76–85. [Google Scholar] [CrossRef] [PubMed]
- Peng, W.; Wang, K.; Zheng, R.; Derwahl, M. 1,25 dihydroxyvitamin D3 inhibits the proliferation of thyroid cancer stem-like cells via cell cycle arrest. Endocr. Res. 2016, 41, 71–80. [Google Scholar] [CrossRef] [PubMed]
- Dackiw, A.P.; Ezzat, S.; Huang, P.; Liu, W.; Asa, S.L. 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. [Google Scholar] [CrossRef] [PubMed]
- Liu, W.; Asa, S.L.; Ezzat, S. 1alpha,25-Dihydroxyvitamin D3 targets PTEN-dependent fibronectin expression to restore thyroid cancer cell adhesiveness. Mol. Endocrinol. 2005, 19, 2349–2357. [Google Scholar] [CrossRef] [PubMed]
- Jacobs, E.T.; Kohler, L.N.; Kunihiro, A.G.; Jurutka, P.W. Vitamin D and colorectal, breast, and prostate cancers: A review of the epidemiological evidence. J. Cancer 2016, 7, 232–240. [Google Scholar] [CrossRef] [PubMed]
- Roskies, M.; Dolev, Y.; Caglar, D.; Hier, M.P.; Mlynarek, A.; Majdan, A.; Payne, R.J. Vitamin D deficiency as a potentially modifiable risk factor for thyroid cancer. J. Otolaryngol. Head Neck Surg. 2012, 41, 160–163. [Google Scholar] [PubMed]
- Sahin, M.; Uçan, B.; Giniş, Z.; Topaloğlu, O.; Güngüneş, A.; Bozkurt, N.Ç.; Arslan, M.S.; Ünsal, İ.Ö.; Akkaymak, E.T.; Demirci, T.; et al. Vitamin D3 levels and insulin resistance in papillary thyroid cancer patients. Med. Oncol. 2013, 30, 589. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.R.; Kim, B.H.; Kim, S.M.; Oh, M.Y.; Kim, W.J.; Jeon, Y.K.; Kim, S.S.; Lee, B.J.; Kim, Y.K.; Kim, I.J. Low serum 25 hydroxyvitamin D is associated with poor clinicopathologic characteristics in female patients with papillary thyroid cancer. Thyroid 2014, 24, 1618–1624. [Google Scholar] [CrossRef] [PubMed]
- Stepien, T.; Krupinski, R.; Sopinski, J.; Kuzdak, K.; Komorowski, J.; Lawnicka, H.; Stepien, H. Decreased 1-25 dihydroxyvitamin D3 concentration in peripheral blood serum of patients with thyroid cancer. Arch. Med. Res. 2010, 41, 190–194. [Google Scholar] [CrossRef] [PubMed]
- Penna-Martinez, M.; Ramos-Lopez, E.; Stern, J.; Hinsch, N.; Hansmann, M.L.; Selkinski, I.; Grünwald, F.; Vorländer, C.; Wahl, R.A.; Bechstein, W.O.; et al. Vitamin D receptor polymorphisms in differentiated thyroid carcinoma. Thyroid 2009, 19, 623–628. [Google Scholar] [CrossRef] [PubMed]
- Penna-Martinez, M.; Ramos-Lopez, E.; Stern, J.; Kahles, H.; Hinsch, N.; Hansmann, M.L.; Selkinski, I.; Grünwald, F.; Vorländer, C.; Bechstein, W.O.; et al. Impaired vitamin D activation and association with CYP24A1 haplotypes in differentiated thyroid carcinoma. Thyroid 2012, 22, 709–716. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- Lizis-Kolus, K.; Hubalewska-Dydejczyk, A.; Trofimiuk-Muldnerz, M.; Sowa-Staszczak, A.; Kowalska, A. Assessment of 25(OH)D3, concentration levels in patients with papillary thyroid cancer compared to patients with Hashimoto’s thyroiditis. Prz. Lek. 2013, 70, 920–925. [Google Scholar] [PubMed]
- Ahn, H.Y.; Chung, Y.J.; Park, K.Y.; Cho, B.Y. Serum 25-Hydroxyvitamin D level does not affect the aggressiveness and prognosis of papillary thyroid cancer. Thyroid 2016, 26, 429–433. [Google Scholar] [CrossRef] [PubMed]
- Danilovic, D.L.; Ferraz-de-Souza, B.; Fabri, A.W.; Santana, N.O.; Kulcsar, M.A.; Cernea, C.R.; Marui, S.; Hoff, A.O. 25-Hydroxyvitamin D and TSH as risk factors or prognostic markers in thyroid carcinoma. PLoS ONE 2016, 11, e0164550. [Google Scholar] [CrossRef] [PubMed]
- Kim, D. Low vitamin D status is not associated with thyroid cancer risk. J. Endocrinol. Metab. 2016, 6, 116–122. [Google Scholar] [CrossRef]
- Choi, Y.M.; Kim, W.G.; Kim, T.Y.; Bae, S.J.; Kim, H.K.; Jang, E.K.; Jeon, M.J.; Han, J.M.; Shong, Y.K.; Kim, W.B. Serum vitamin D3 levels are not associated with thyroid cancer prevalence in euthyroid subjects without autoimmune thyroid disease. Korean J. Intern. Med. 2017, 32, 102–108. [Google Scholar] [CrossRef] [PubMed]
- Mack, W.J.; 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. [Google Scholar] [CrossRef]
- Greenlee, H.; White, E.; Patterson, R.E.; Kristal, A.R. Supplement use among cancer survivors in the Vitamins and Lifestyle (VITAL) study cohort. J. Altern. Complement. Med. 2004, 10, 660–666. [Google Scholar] [CrossRef] [PubMed]
- O’Grady, T.J.; Kitahara, C.M.; DiRienzo, A.G.; Gates, M.A. The association between selenium and other micronutrients and thyroid cancer incidence in the NIH-AARP Diet and Health Study. PLoS ONE 2014, 9, e110886. [Google Scholar] [CrossRef] [PubMed]
- Zhang, L.R.; Sawka, A.M.; Adams, L.; Hatfield, N.; Hung, R.J. Vitamin and mineral supplements and thyroid cancer: A systematic review. Eur. J. Cancer Prev. 2013, 22, 158–168. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- Clinckspoor, I.; Hauben, E.; Verlinden, L.; Van den Bruel, A.; Vanwalleghem, L.; Vander Poorten, V.; Delaere, P.; Mathieu, C.; Verstuyf, A.; Decallonne, B. Altered expression of key players in vitamin D metabolism and signaling in malignant and benign thyroid tumors. J. Histochem. Cytochem. 2012, 60, 502–511. [Google Scholar] [CrossRef] [PubMed]
- Izkhakov, E.; Somjen, D.; Sharon, O.; Knoll, E.; Aizic, A.; Fliss, D.M.; Limor, R.; Stern, N. Vitamin D receptor expression is linked to potential markers of human thyroid papillary carcinoma. J. Steroid Biochem. Mol. Biol. 2016, 159, 26–30. [Google Scholar] [CrossRef] [PubMed]
- Choi, J.Y.; Yi, J.W.; Lee, J.H.; Song, R.Y.; Yu, H.; Kwon, H.; Chai, Y.J.; Kim, S.J.; Lee, K.E. VDR mRNA overexpression is associated with worse prognostic factors in papillary thyroid carcinoma. Endocr. Connect. 2017, 6, 172–178. [Google Scholar] [CrossRef] [PubMed]
- Gandini, S.; Gnagnarella, P.; Serrano, D.; Pasquali, E.; Raimondi, S. Vitamin D receptor polymorphisms and cancer. Adv. Exp. Med. Biol. 2014, 810, 69–105. [Google Scholar] [PubMed]
- Haghpanah, V.; Ghaffari, S.H.; Rahimpour, P.; Abbasi, A.; Saeedi, M.; Pak, H.; Alborzi, F.; Barzegar, S.; Heshmat, R.; Alimoghadam, K.; et al. Vitamin D receptor gene polymorphisms in patients with thyroid cancer. Gene Ther. Mol. Biol. 2007, 11, 299–304. [Google Scholar]
- Bizzaro, G.; Shoenfeld, Y. Vitamin D and thyroid autoimmune diseases: The known and the obscure. Immunol. Res. 2015, 61, 107–109. [Google Scholar] [CrossRef] [PubMed]
- Mazokopakis, E.E.; Kotsiris, D.A. Hashimoto’s autoimmune thyroiditis and vitamin D deficiency. Current aspects. Hell. J. Nucl. Med. 2014, 17, 37–40. [Google Scholar] [CrossRef] [PubMed]
- Muscogiuri, G.; Mitri, J.; Mathieu, C.; Badenhoop, K.; Tamer, G.; Orio, F.; Mezza, T.; Vieth, R.; Colao, A.; Pittas, A. Mechanisms in endocrinology: Vitamin D as a potential contributor in endocrine health and disease. Eur. J. Endocrinol. 2014, 171, R101–R110. [Google Scholar] [CrossRef] [PubMed]
Sources | Study Subjects | Low Vitamin D Status (25(OH)D Level (nmol/L)) | |
---|---|---|---|
Criteria | Notable Findings | ||
Kivity et al., 2011 [21] | 50 AITD (28 HT, 22 GD), 42 non-AITD, 98 healthy controls | <25 | 70% of HT, 64% of GD, 52% of non-AITD patients, 30% of controls (SD) |
Tamer et al., 2011 [22] | 161 HT, 162 healthy controls | <75 | 91.9% of HT, 63% of controls (SD) |
Bozkurt et al., 2013 [23] | 180 euthyroid HT, 180 newly diagnosed HT, 180 healthy controls | <25 | 48.3% vs. 35% vs. 20.5% of each groups (SD); correlated with thyroid volume (r = 0.15), anti-TPO (r = −0.36), anti-Tg levels (r = −0.34) (SD) |
Mansournia et al., 2014 [24] | 41 hypothyroid HT, 45 healthy controls | NA | inverse association with HT (OR 0.81 for 12.5 nmol/L increase in 25(OH)D) (SD) |
Shin et al., 2014 [25] | 111 AITD, 193 non-AITD patients | NA | 31.5 nmol/L in AITD, 36.2 nmol/L in non-AITD (SD); negative correlation between 25(OH)D and anti-TPO levels (r = −0.252) (SD) |
Unal et al., 2014 [26] | 254 newly diagnosed HT, 27 GD, 124 healthy controls | NA | 37.2 vs. 48.4 vs. 56.2 nmol/L in each groups (SD); correlated with anti-Tg (r = −0.14), anti-TPO levels (r = −0.18) (SD) |
Choi et al., 2014 [27] | 673 anti-TPO (+), 6012 anti-TPO (−) subjects for routine health checkups | <25 (D) 25–75 (I) >75 (S) | 50.7 nmol/L in anti-TPO (+), 56.4 nmol/L in anti-TPO (−) in premenopausal women (SD); anti-TPO (+) 21.2%, 15.5.%, and 12.6% in D, I, S groups in premenopausal women (SD); OR 1.95 for TPO-Ab (+) (SD) |
Wang et al., 2015 [28] | 1714 subjects for population-based health survey | NA | correlation (r = −0.12) between 25(OH)D and anti-Tg levels only in female subjects (SD) |
Kim, 2016 [29] | 369 AITD (221 HT. 148 GD), 407 non-AITD patients | <75 | 46.1% of AITD, 48.9% of HT, 41.9% of GD, 37.1% of non-AITD (SD); lower vitamin D status in overt hypothyroid HT than other HT groups or non-AITD (SD) |
Muscogiuri et al., 2016 [31] | 168 elderly subjects | <50 (D) | prevalence of AIT 28% vs. 8% in D and non-D groups (SD); correlation between 25(OH) D and anti-TPO levels (r = −0.27) (SD) |
Camurdan et al., 2012 [32] | 152 children (78 recently diagnosed HT, 74 controls) | <32.5 | 73.1% of HT, 17.6% of controls (SD); 31.2 vs. 57.9 nmol/L (SD); inverse correlation with anti-TPO levels (r = −0.30) (SD) |
Evliyaoğlu et al., 2015 [33] | 169 Turkish children (90 HT, 79 healthy controls) | <50 | 71.1% of HT, 51.9% of controls (SD); 41.6 vs. 52.4 nmol/L (SD); OR 2.28 for HT risk in 25(OH)D <50 nmol/L |
Metwalley et al., 2016 [34] | 112 Egyptian children (56 AIT, 56 healthy, age- and sex-matched controls | <12.5 (DD) 12.5–37.5 (D) 37.5–50 (I) 50–250 (S) | vitamin D deficiency rate 71.4% of AIT, 21.4% of controls (SD); 16.2 vs. 33.9 nmol/L (SD); negative correlations between 25(OH)D and disease duration, anti-TPO, anti-Tg, and TSH (r = −0.676, −0.533, −0.487, −0.445, respectively) (SD) |
Goswami et al., 2009 [35] | 642 students, teachers and staff aged 16–60 years | <25 | no association with anti-TPO positivity; weak inverse correlation between 25(OH)D and anti-TPO levels (r = −0.08) |
Effraimidis et al., 2012 [36] | 803 subjects from the Amsterdam AITD cohort | NA | no association with early stages of thyroid autoimmunity |
D’Aurizio et al., 2015 [11] | 100 AITD (52 HT, 48 GD), 126 healthy controls | <50 nmol/L | no difference |
Yasmeh et al., 2016 [37] | 97 HT, 88 healthy controls | <50 (D) 50–74.9 (I) ≥75 (S) | no association between HT and vitamin D deficiency; S 51.7% of HT vs. 31.1% controls in females (SD); 76.8 vs. 68.8 nmol/L in HT and control females (SD); correlation between 25(OH)D and anti-TPO levels (r = 0.436) in males (SD) |
Yasuda et al., 2012 [38] | 72 females (26 new onset GD, healthy controls) | <37.5 nmol/L | 65.4% of GD, 32.4% of controls (SD); 35.9 vs. 42.7 nmol/L (SD); correlation between 25(OH)D and thyroid volume (r = −0.45) (SD) |
Yasuda et al., 2013 [39] | 103 females (36 non-remission GD, 18 remission GD, 49 controls) | NA | 36.2 vs. 45.4 vs. 46.4 nmol/L (SD) |
Zhang et al., 2015 [40] | 70 GD, 70 controls | <50 nmol/L | higher vitamin D deficiency rates and lower 25(OH)D levels in anti-TSHR (+) GD than anti-TSHR (−) GD or controls (SD); inverse correlation between 25(OH)D and anti-TSHR levels in anti-TSHR (+) GD |
Sources | Study Subjects | Low Vitamin D Status (25(OH)D Level (nmol/L)) | |
---|---|---|---|
Criteria | Notable Findings | ||
Roskies et al., 2012 [61] | 212 patients undergoing thyroidectomy | <37.5 (D) | malignancy rate 75% vs. 37.5% in D and non-D group (RR 2.0, 95% CI 1.07–2.66) (SD) |
Sahin et al., 2013 [62] | 344 PTC, 116 controls | <50 | 70.6% of PTC, 59.3% of controls; 42.4 vs. 47.4 nmol/L (SD); association between tumor diameter and log-25(OH)D (B = 0.207) (SD) |
Kim et al., 2014 [63] | 548 females undergoing total thyroidectomy for PTC | <46.2 (median) | higher risk of T stage 3/4, LNM, lateral LNM, stage III/IV (SD); lower 25(OH)D levels in patients with a tumor size >1 cm or LNM (SD) |
Stepien et al., 2010 [64] | 50 TC (27 PTC, 16 FTC, 7 ATC), 34 MNG, 26 healthy controls | NA | no difference in 25(OH)D levels; lower 1,25(OH)2D levels in TC than controls (SD); inverse relationship between 1,25(OH)2D levels and tumor stage (SD) |
Penna-Martinez et al., 2009 [65] | 172 TC (132 PTC, 40 FTC), 321 healthy controls | <50 | no difference vitamin D deficiency rates and 25(OH)D levels; higher 1,25(OH)2D deficiency and lower 1,25(OH)2D levels in TC than controls (SD) |
Penna-Martinez et al., 2012 [66] | 253 TC (205 PTC, 48 FTC), 302 healthy controls | <25 (DD) 25–50 (D) 50–75 (I) >75 (S) | no difference in vitamin D status and 25(OH)D levels; lower 1,25(OH)2D levels in TC than controls (SD); lower 25(OH)D and 1,25(OH)2D levels in TC patients with certain CYP24A1 haplotypes |
Laney et al., 2010 [67] | 69 TC (45 in remission, 24 active), 42 benign thyroid nodule patients | <75 | no difference vitamin D deficiency rates and 25(OH)D levels |
Jonklaas et al., 2013 [68] | 65 euthyroid patients undergoing thyroidectomy | NA | no association between 25(OH)D levels and malignancy rate, stage, or other prognostic features |
Lizis-Kolus et al., 2013 [69] | 80 females (40 PTC, 40 HT) | NA | no association between 25(OH)D levels and malignancy rate or stage |
Ahn et al., 2016 [70] | 820 PTC | <24.7 24.7–32.9 33.0–44.1 44.2–110.0 | no association between vitamin D status and disease aggressiveness or poor outcomes |
Danilovic et al., 2016 [71] | 433 patients undergoing thyroidectomy (199 TC, 234 benign nodule) | <50 | no difference in vitamin D deficiency rates and 25(OH)D levels |
Kim, 2016 [72] | 410 patients undergoing US-guided FNA for thyroid nodules (44 TC, 366 benign) | <75 | no difference in vitamin D deficiency and 25(OH)D levels; no association with cancer stage or other prognostic features |
Choi et al., 2017 [73] | 5186 euthyroid subjects without AITD undergoing routine health check-ups (53 TC) | <25 (D) 25–75 (I) 75–125 (S) >125 (E) | no difference in vitamin D status and 25(OH)D levels |
© 2017 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kim, D. The Role of Vitamin D in Thyroid Diseases. Int. J. Mol. Sci. 2017, 18, 1949. https://doi.org/10.3390/ijms18091949
Kim D. The Role of Vitamin D in Thyroid Diseases. International Journal of Molecular Sciences. 2017; 18(9):1949. https://doi.org/10.3390/ijms18091949
Chicago/Turabian StyleKim, Dohee. 2017. "The Role of Vitamin D in Thyroid Diseases" International Journal of Molecular Sciences 18, no. 9: 1949. https://doi.org/10.3390/ijms18091949