25-Hydroxy vitamin D (25(OH)D)deficiency is linked with predisposition to autoimmune type 1 diabetes and multiple sclerosis. Our objective was to assess the relationship between serum 25(OH)D levels and thyroid autoimmunity. Subjects included students, teachers and staff aged 16-60 years (total 642, 244 males, 398 females). Serum free thyroxine, thyroid-stimulating hormone (TSH), and thyroid peroxidase autoantibodies (TPOAb), intact parathyroid hormone and 25(OH)D were measured by electrochemiluminescence and RIA, respectively. Thyroid dysfunction was defined if (1) serum TSH $ 5 mU/ml and TPOAb . 34 IU/ml or (2) TSH $ 10 mU/ml but normal TPOAb. The mean serum 25(OH)D of the study subjects was 17·5 (SD 10·2) nmol/l with 87 % having values #25 nmol/l. TPOAb positivity was observed in 21 % of subjects. The relationship between 25(OH)D and TPOAb was assessed with and without controlling for age and showed significant inverse correlation (r 2 0·08, P¼ 0·04) when adjusted for age. The prevalence of TPOAb and thyroid dysfunction were comparable between subjects stratified according to serum 25(OH)D into two groups either at cut-off of #25 or . 25 nmol/l or first and second tertiles. Until recently, vitamin D deficiency was considered to be rare in India because of abundant sunshine (1,2) . However, a systematic study carried out in the year 2000 in Delhi showed the presence of low 25-hydroxy vitamin D (25(OH)D) in a majority of subjects including newborns, their mothers, healthy physicians, nurses, soldiers and those with vitiligo and albinism. Based on these study groups, subnormal serum 25(OH)D levels of Asian Indians could be linked to their skin pigmentation and poor sunshine exposure (1,3) . Subsequently, a series of studies have documented widespread hypovitaminosis D in north as well as south India (3 -5) . Besides bone mineral homeostasis, 25(OH)D deficiency has been associated with a wide range of non-skeletal effects including predisposition towards autoimmune disorders (6 -8) .The demonstration of vitamin D receptor in monocytes, dendritic cells and activated T cells indicates significant interaction between vitamin D and the immune system (6,7) . While the molecular mechanisms linking vitamin D with autoimmunity are under investigation, in vitro studies indicate an immunomodulatory effect of 1,25(OH)D on Th 1 , Th 2 , T regulator and dendritic cells leading to a shift towards activation of Th2 cells (6,7) . Clinical relevance of the mechanism is indicated by a number of studies showing increased prevalence of autoimmune disease such as multiple sclerosis in Canada and the northern part of the USA receiving less sunshine. Vitamin D supplementation resulted in decreased prevalence of autoimmune disorders such as type 1 diabetes and multiple sclerosis. A recent meta-analysis showed 29 % reduction in the risk of type 1 diabetes in children receiving vitamin D supplementation (9,10)

The frequencies of TPOAb and thyroid dysfunction were not significantly higher in patients with SIH than in healthy controls, unlike in patients with T1D and POF.

Thus, spondyloarthropathy is a distinct clinical entity in patients with SIH. Its salient clinical features include presence of syndesmophytes at the thoracic or thoraco-lumbar spine, mild sacroiliitis, calcification at the acetabular margin of hip, preserved bone density, equal distribution in both sexes and lack of HLA-B27 association. Presence of spondyloarthropathy, like basal ganglia calcification, is associated with longer duration of hypoparathyroidism. It is important to differentiate hypoparathyroid-related spondyloarthropathy from ankylosing spondylitis because the management for the two disorders is different.

IP performed the best in detecting CaSRAbs in 12.9% of hypoparathyroid patients. Although CaSRAbs were functionally inert, its clinical relevance remains due to 100% specificity. Limited prevalence of CaSRAb suggests heterogeneity in the etiology of idiopathic hypoparathyroidism or the presence of CaSR epitopes other than those measured in the current study.

The pathogenetic mechanisms involved in the development of sporadic idiopathic hypoparathyroidism are currently under investigation. Although autoantibodies against the calcium-sensing receptor (CaSR) have been implicated to play a role, these could be demonstrated in only 49% of a group of 51 patients with sporadic idiopathic hypoparathyroidism that we previously studied. Therefore, we investigated 49 of these patients further, regardless of their antibody status, and looked for mutations in the section of the PTH gene sequence that coded for prepro-PTH as well as the 3'-untranslated region (3'-UTR) of the gene, which is believed to be involved in the stability of its mRNA. We also examined the relationship between the clinical manifestations of the disease and the occurrences of two commonly observed single nucleotide polymorphisms (SNPs) in the PTH gene. In 49 of the patients with idiopathic hypoparathyroidism and in 55 healthy controls, the SNPs were characterized by restriction analysis using DraII and BstBI enzymes. In a subset of these patients, exons 2 and 3 of the PTH gene (n = 37) and its 3'-UTR region (n = 40) were also sequenced. No mutations were observed in the segment of the PTH gene coding for the signal peptide, prohormone, or the 3'-UTR region. However, three well described SNPs were observed: 1) an A-->G substitution in intron 1 in 35.1% of the patients; 2) a G-->A substitution in intron 2, characterized by BstBI, in one or both alleles in 27%; and 3) a C-->A substitution at codon 52 (CGA) of exon 3, characterized by DraII, in one or both alleles in 59.7% of the patients. There was no significant difference in the frequency of occurrence of these SNPs between the patient and the control groups. Furthermore, the mean age at onset of symptoms, body mass index, frequency of cataract, tetany, convulsion, basal ganglia calcification, serum calcium, inorganic phosphorus, and intact PTH were not significantly different between patients with and without the above-described SNPs. Thus, the data from this report demonstrate that in patients with sporadic idiopathic hypoparathyroidism, neither the clinical manifestations nor the biochemical indexes of the disease are related to the occurrence of mutations or SNPs in the PTH gene. Because neither patient nor control samples exhibited any variations in the sequence of their 3'-UTR regions, it is unlikely that mRNA instability is a factor in the pathogenesis of the disease. Additional studies are required to investigate the role of other genes and autoantigens that may be involved in the genesis of idiopathic hypoparathyroidism.