Mechanisms in endocrinology: vitamin D as a potential contributor in endocrine health and disease.

OBJECTIVE It has been suggested that vitamin D may play a role in the pathogenesis of several endocrine diseases, such as hyperparathyroidism, type 1 diabetes (T1DM), type 2 diabetes (T2DM), autoimmune thyroid diseases, Addison's disease and polycystic ovary syndrome (PCOS). In this review, we debate the role of vitamin D in the pathogenesis of endocrine diseases. METHODS Narrative overview of the literature synthesizing the current evidence retrieved from searches of computerized databases, hand searches and authoritative texts. RESULTS Evidence from basic science supports a role for vitamin D in many endocrine conditions. In humans, inverse relationships have been reported not only between blood 25-hydroxyvitamin D and parathyroid hormone concentrations but also with risk of T1DM, T2DM, and PCOS. There is less evidence for an association with Addison's disease or autoimmune thyroid disease. Vitamin D supplementation may have a role for prevention of T2DM, but the available evidence is not consistent. CONCLUSIONS Although observational studies support a potential role of vitamin D in endocrine disease, high quality evidence from clinical trials does not exist to establish a place for vitamin D supplementation in optimizing endocrine health. Ongoing randomized controlled trials are expected to provide insights into the efficacy and safety of vitamin D in the management of endocrine disease.

[1]  C. Mathieu,et al.  Dietary Supplementation With High Doses of Regular Vitamin D3 Safely Reduces Diabetes Incidence in NOD Mice When Given Early and Long Term , 2014, Diabetes.

[2]  C. Mathieu,et al.  1,25-Dihydroxyvitamin D3 Promotes Tolerogenic Dendritic Cells with Functional Migratory Properties in NOD Mice , 2014, The Journal of Immunology.

[3]  M. Bugliani,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. , 2014, Endocrinology.

[4]  Ishir Bhan,et al.  Vitamin D-binding protein and vitamin D status of black Americans and white Americans. , 2013, The New England journal of medicine.

[5]  Miranda E. Kroehl,et al.  Association between vitamin D metabolism gene polymorphisms and risk of islet autoimmunity and progression to type 1 diabetes: the diabetes autoimmunity study in the young (DAISY). , 2013, The Journal of clinical endocrinology and metabolism.

[6]  D. Yavuz,et al.  Vitamin D receptor gene ApaI, TaqI, FokI and BsmI polymorphisms in a group of Turkish patients with Hashimoto's thyroiditis. , 2013, Minerva endocrinologica.

[7]  A. Maciejewski,et al.  [Vitamin D in the etiopathogenesis of autoimmune thyroiditis]. , 2013, Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego.

[8]  J. Manson,et al.  Blood 25-Hydroxy Vitamin D Levels and Incident Type 2 Diabetes , 2013, Diabetes Care.

[9]  Wei-fang Li,et al.  Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis , 2013, Endocrine.

[10]  B. Mesçi,et al.  Role of Vitamin D in the Immune System , 2013 .

[11]  C. Mathieu,et al.  Effects of vitamin D on antigen‐specific and non‐antigen‐specific immune modulation: relevance for type 1 diabetes , 2013, Pediatric diabetes.

[12]  B. Roep,et al.  Regulatory Multitasking of Tolerogenic Dendritic Cells – Lessons Taken from Vitamin D3-Treated Tolerogenic Dendritic Cells , 2013, Front. Immunol..

[13]  S. Bojesen,et al.  Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and metaanalysis. , 2013, Clinical chemistry.

[14]  T. Delibaşı,et al.  The association between severity of vitamin D deficiency and Hashimoto's thyroiditis. , 2013, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[15]  M. Lee,et al.  High-Dose Vitamin D Supplementation in People With Prediabetes and Hypovitaminosis D , 2013, Diabetes Care.

[16]  C. Mathieu,et al.  1,25-Dihydroxyvitamin D3 curtails the inflammatory and T cell stimulatory capacity of macrophages through an IL-10-dependent mechanism. , 2012, Immunobiology.

[17]  M. Atkinson.  The pathogenesis and natural history of type 1 diabetes. , 2012, Cold Spring Harbor perspectives in medicine.

[18]  I. Shimomura,et al.  Serum vitamin D levels are decreased in patients without remission of Graves’ disease , 2012, Endocrine.

[19]  C. Mathieu,et al.  Extraskeletal effects of vitamin D. , 2012, Endocrinology and metabolism clinics of North America.

[20]  A. Pontecorvi,et al.  Low levels of 25(OH)D and insulin-resistance: 2 unrelated features or a cause-effect in PCOS? , 2012, Clinical nutrition.

[21]  A. Bideci,et al.  Vitamin D status in children with Hashimoto thyroiditis , 2012, Journal of pediatric endocrinology & metabolism : JPEM.

[22]  F. Bienaimé,et al.  Vitamin D and primary hyperparathyroidism (PHPT). , 2012, Annales d'endocrinologie.

[23]  R. Seemann,et al.  Parameters for calcium metabolism in women with polycystic ovary syndrome who undergo clomiphene citrate stimulation: a prospective cohort study. , 2012, European journal of endocrinology.

[24]  I. Shimomura,et al.  Serum vitamin D levels are decreased and associated with thyroid volume in female patients with newly onset Graves’ disease , 2012, Endocrine.

[25]  B. Lie,et al.  Multiple loci in the HLA complex are associated with Addison's disease. , 2011, The Journal of clinical endocrinology and metabolism.

[26]  G. Tamer,et al.  Relative vitamin D insufficiency in Hashimoto's thyroiditis. , 2011, Thyroid : official journal of the American Thyroid Association.

[27]  F. Hu,et al.  Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. , 2011, The American journal of clinical nutrition.

[28]  C. Gordon,et al.  Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. , 2011, The Journal of clinical endocrinology and metabolism.

[29]  T. Pieber,et al.  Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: A pilot study , 2011, Journal of endocrinological investigation.

[30]  Y. Shoenfeld,et al.  Vitamin D and autoimmune thyroid diseases , 2011, Cellular and Molecular Immunology.

[31]  T. Spector,et al.  Inherited Variation in Vitamin D Genes Is Associated With Predisposition to Autoimmune Disease Type 1 Diabetes , 2011, Diabetes.

[32]  E. Husebye,et al.  Cellular immunity and immunopathology in autoimmune Addison's disease , 2011, Molecular and Cellular Endocrinology.

[33]  G. Ghirlanda,et al.  No Protective Effect of Calcitriol on β-Cell Function in Recent-Onset Type 1 Diabetes , 2010, Diabetes Care.

[34]  J. Lundqvist,et al.  1alpha,25-Dihydroxyvitamin D3 affects hormone production and expression of steroidogenic enzymes in human adrenocortical NCI-H295R cells. , 2010, Biochimica et biophysica acta.

[35]  C. Mathieu,et al.  Vitamin D: modulator of the immune system. , 2010, Current opinion in pharmacology.

[36]  E. Bonifacio,et al.  No Effect of the 1α,25-Dihydroxyvitamin D3 on β-Cell Residual Function and Insulin Requirement in Adults With New-Onset Type 1 Diabetes , 2010, Diabetes Care.

[37]  G. Dranitsaris,et al.  A phase 2 trial exploring the effects of high‐dose (10,000 IU/day) vitamin D3 in breast cancer patients with bone metastases , 2010, Cancer.

[38]  J. Sowiński,et al.  Association of the CYP27B1 C(−1260)A Polymorphism with Autoimmune Addison's Disease , 2009, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[39]  S. Verma,et al.  Low levels of vitamin D in North Indian children with newly diagnosed type 1 diabetes , 2009, Pediatric diabetes.

[40]  T. Pieber,et al.  Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. , 2009, European journal of endocrinology.

[41]  M. Yavropoulou,et al.  Role of vitamin D treatment in glucose metabolism in polycystic ovary syndrome. , 2009, Fertility and sterility.

[42]  A. Avenell,et al.  Vitamin D supplementation and type 2 diabetes: a substudy of a randomised placebo-controlled trial in older people (RECORD trial, ISRCTN 51647438). , 2009, Age and ageing.

[43]  A. Bener,et al.  High prevalence of vitamin D deficiency in type 1 diabetes mellitus and healthy children , 2009, Acta Diabetologica.

[44]  M. Kurdoğlu,et al.  Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome , 2009, Archives of Gynecology and Obstetrics.

[45]  C. Mathieu,et al.  Unaltered Diabetes Presentation in NOD Mice Lacking the Vitamin D Receptor , 2008, Diabetes.

[46]  M. Holick.  Vitamin D deficiency. , 2007, The New England journal of medicine.

[47]  M. Harris,et al.  Australian children and adolescents with type 1 diabetes have low vitamin D levels , 2007, The Medical journal of Australia.

[48]  J. Ludvigsson,et al.  Vitamin D supplementation and diabetes‐related autoimmunity in the ABIS study , 2007, Pediatric diabetes.

[49]  L. Nyström,et al.  Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS) , 2006, Diabetologia.

[50]  P. Lips.  Vitamin D physiology. , 2006, Progress in biophysics and molecular biology.

[51]  R. Kimmig,et al.  Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. , 2006, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[52]  P. Pozzilli,et al.  Low Levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in Patients with Newly Diagnosed Type 1 Diabetes , 2005, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[53]  A. Hermann,et al.  Higher bone mineral density in Caucasian, hirsute patients of reproductive age. Positive correlation of testosterone levels with bone mineral density in hirsutism , 2005, Clinical endocrinology.

[54]  Y. Shoenfeld,et al.  Coexistence of thyroid autoimmunity with other autoimmune diseases: Friend or foe? Additional aspects on the mosaic of autoimmunity , 2005, Autoimmunity.

[55]  L. Adorini,et al.  A Vitamin D Analog Down-Regulates Proinflammatory Chemokine Production by Pancreatic Islets Inhibiting T Cell Recruitment and Type 1 Diabetes Development1 , 2004, The Journal of Immunology.

[56]  M. Segni,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. , 2004, European journal of endocrinology.

[57]  J. Todd,et al.  Lack of association of the vitamin D receptor gene with Graves’ disease in UK Caucasians , 2004, Clinical endocrinology.

[58]  J. Holloszy,et al.  Ca2+ and AMPK both mediate stimulation of glucose transport by muscle contractions. , 2004, Diabetes.

[59]  C. Mathieu,et al.  Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice , 2004, Diabetologia.

[60]  L. C. Stene,et al.  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. , 2003, The American journal of clinical nutrition.

[61]  H. DeLuca,et al.  Oral administration of 1,25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus. , 2003, Archives of biochemistry and biophysics.

[62]  E. Wolf,et al.  Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[63]  N. Dávila,et al.  Identification of a Vitamin D response element in the human insulin receptor gene promoter , 2003, The Journal of Steroid Biochemistry and Molecular Biology.

[64]  M. Pani,et al.  Vitamin D receptor genotype is associated with Addison's disease. , 2002, European journal of endocrinology.

[65]  G. Åkerström,et al.  25-hydroxyvitamin D3-1α-hydroxylase expression in normal and pathological parathyroid glands , 2002 .

[66]  Elina Hyppönen,et al.  Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study , 2001, The Lancet.

[67]  M. Taniyama,et al.  Vitamin D receptor gene polymorphism is associated with Graves' disease in the Japanese population. , 2000, The Journal of clinical endocrinology and metabolism.

[68]  P. Magnus,et al.  Use of cod liver oil during pregnancy associated with lower risk of Type I diabetes in the offspring , 2000, Diabetologia.

[69]  T. Katagiri,et al.  Vitamin D receptor initiation codon polymorphism in Japanese patients with Graves' disease. , 2000, Thyroid : official journal of the American Thyroid Association.

[70]  J. Bilezikian,et al.  Vitamin D and calcium dysregulation in the polycystic ovarian syndrome , 1999, Steroids.

[71]  R. Wernyj,et al.  Genomic mechanisms involved in the pleiotropic actions of 1,25-dihydroxyvitamin D3. , 1996, The Biochemical journal.

[72]  C. Mathieu,et al.  Prevention of autoimmune diabetes in NOD mice by 1,25 dihydroxyvitamin D3 , 1994, Diabetologia.

[73]  C. Hales,et al.  The role of calcium and magnesium in insulin secretion from rabbit pancreas studied in vitro , 1967, Diabetologia.

[74]  S. Silverberg,et al.  Normocalcemic primary hyperparathyroidism. , 2013, Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry.

[75]  L. Laffel,et al.  Significant vitamin D deficiency in youth with type 1 diabetes mellitus. , 2009, The Journal of pediatrics.

[76]  R. Marwaha,et al.  Juvenile Autoimmune Thyroiditis , 2007, Journal of pediatric endocrinology & metabolism : JPEM.

[77]  C. Beaufort.  The EURODIAB Substudy 2 Study Group Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus , 1999 .

[78]  C. Mathieu,et al.  Prevention of type I diabetes in nonobese diabetic mice by late intervention with nonhypercalcemic analogs of 1,25-dihydroxyvitamin D3 in combination with a short induction course of cyclosporin A. , 1998, Endocrinology.