- The Journal of the Association of Physicians of India, 2023, Volume: 71, Issue:1
A Prospective Study to Evaluate the Possible Role of Cholecalciferol Supplementation on Autoimmunity in Hashimoto's Thyroiditis Biva Bhakat1 , Jyotirmoy Pal2 , Sukdeb Das3 , Sumit Kr Charaborty4 1,3Nil Ratan Sircar Medical College, Kolkata, 2 RG Kar Medical College and Hospital, 4 North Bengal Medical College, Siliguri Introduction: Hashimoto thyroiditis (HT) is an autoimmune disease that destroys thyroid cells by antibody and call-mediated immune processes. Hashimoto thyroiditis is the commonest cause of goitre in iodine-sufficient regions.[1] The aetiology of Hashimoto disease is very poorly understood. Most patients develop antibodies to a variety of thyroid antigens, the most common of which is anti-thyroid peroxidase (anti-TPO). Many also form antithyroglobulin (anti-Tg) and TSH receptor blocking antibodies (TBII). These antibodies attack the thyroid tissue, eventually leading to inadequate production of thyroid hormone. There is a small subset of the population, around 10-15% with the clinically evident disease, that are serum antibody-negative.[2][3] The mechanisms underlying the assumption that vitamin D is linked with autoimmunity are not clear but probably are associated with its anti-inflammatory and immunomodulatory functions. The dendritic cells are antigen-presenting cells originating from bone marrow and also a primary target for the immunomodulatory activity of vitamin D. 1,25[OH]2D has direct immunomodulatory effects at the level of the T cell vitamin D receptor. Together, these immunomodulatory effects can lead to the protection of target tissues, such as thyroid cells in autoimmune diseases. Considering that in HT, a disorder of T cell-mediated immunity, immunologic attack is triggered when thyrocytes express MHC class II surface HLA-DR antigens, a process induced by the production of Th1 type inflammatory cytokines (especially IFN-γ). Moreover, at another stage, after being activated by T cells, B cells' ongoing proliferation might be inhibited and apoptosis might be induced by 1,25[OH]2D. Thus, 1,25[OH]2D might decrease antibodies that react with thyroid antigens. The exact levels of vitamin D that are sufficient to improve the immune regulatory function and lead to an effective immune response, should be investigated. Several clinical studies have reported a low vitamin D status in AITD or HT, indicating an association between vitamin D deficiency and thyroid autoimmunity. If supplementation of the Vitamin D decreased thyroid an. Most studies have shown an association between low vitamin D status and pathogenesis of AITD, especially HT. However, there are only few preliminary interventional studies for HT. whether vitamin D supplementation is beneficial for AITD or HT, should be evaluated. Treatment of HT mainly based on thyroid hormone supplementation, so if a beneficial role of vitamin D supplementation is identified/ confirmed, it will be helpful in the treatment of patients with HT and may be a part of treatment of HT patients.. Evaluating the role of vitamin D on an excessive thyroid immune response.. Study area: N.R.S. Medical college and hospital, Kolkata (Department of General Medicine).. 1 year (January,2019 to December,2019 Sample size: 100 patients both male and female. Sample Design: Patients attending outpatient dept in N.R.S medical college.. Prospective, hospital based, single centre study.. Newly diagnosed patients (age >18 years and of both sexes) with HT and vitamin D deficiency.. Patients suffering from: Other autoimmune diseases. Chronic illnesses like diabetes mellitus, chronic kidney disease, chronic liver disease, malignancy. Pregnancy Study tools: Estimation from serum: TSH. Free thyroxine (FT4) 25 hydroxy vitamin D Anti-thyroid peroxidase (anti-TPO) antibody' Study techniques: This is a prospective study conducted in N.R.S Medical college, Kolkata, India. Total 100 adult patients of both sexes diagnosed with HT and vitamin D deficiency (vit D<30 ng/ml)12, having none of the exclusion criteria and getting treatment on out-patient department basis, who gave informed consent were included in our study. Blood samples drawn for anti TPO antibody and 25hydroxy vitamin D from all the participants. The correlations between serum Vit D and anti TPO antibody were measured and presented by correlation coef ficient (r2). Study participants are randomly assigned into two groups by random permuted block. Cholecalciferol supplement given in the dose of 60,000 IU weekly for 8 weeks in one group (n = 50). Another group (n = 50) were given placebo (empty soft gelatine capsule). At the onset of the study, patients were requested to keep their habitual diet and routine level of physical activity throughout the study period and not to take any medication that might affect their reproductive physiology. Compliance to the consumption of supplement and placebo was examined by empty blister packets. However, 2 patients from cholecalciferol group and 1 patient from control group lost to follow up. After 8 weeks blood anti TPO antibody level measured in both the groups (n = 48 & 49 in 2 group). The change in the mean value of anti TPO antibody measured and statistical significance of the change checked. Results considered significant or non-significant when P> or < 0.05, respectively. TSH, T4 measurement Performed with chemiluminescence using ADVIA Centaur XP Immunoassay System. Work plan: Study was done over 12 months. Data collected and compilation done and then statistical analysis done by standard statistical method.. For statistical analysis data were entered into a Microsoft excel spreadsheet and then analyzed by SPSS (version 27.0; SPSS Inc., Chicago, IL, USA) and GraphPad Prism version 5. p-value ≤ 0.05 was considered for statistically significant. The Negative Correlation was found between Serum 25 hydroxy vitamin D (ng/ml) vs Serum TSH (mU/L) which was statistically significant. Distribution of mean serum anti-TPO antibody level (IU/ml) [mean±SD] in both groups before and after intervention 
Reduction of serum anti-TPO antibody level in cholecalciferol group is 30.5% and reduction of serum anti-TPO antibody level in placebo group is 16.5%.. This study is carried out with the total no. of 100 outdoor based patients of diagnosed Hashimoto's Thyroiditis (elevated Anti-thyroid peroxidase antibody) and vitamin D deficiency (vit D < 30 ng/mL)12 in Nil Ratan Sircar medical college and hospital within the mentioned study period. The study focussed on evaluating the role of vitamin D on an excessive thyroid immune response i.e. the effect of vitamin D supplementation on thyroid autoimmunity and that low vitamin D levels and the risk of HT are closely associated and the potential application of vitamin D in the treatment of AITD. The result demonstrates a negative Correlation between Serum 25 hydroxy vitamin D (ng/mL) vs anti TPO antibody (IU/ml) which was statistically significant. Pearson Correlation Coefficient (r)= -0.775, p value = 0.0001. Goswami et al. conducted a community-based survey on 642 adults to investigate the relationship between serum vitamin D concentrations and thyroid autoimmunity. Their results highlighted a significant inverse association between 25(OH)D3 and TPO Ab levels [40]. This inverse correlation was substantiated in the following studies.[5-8] As regards thyroid function in the context of HT, Mackawy and co-workers demonstrated a strong negative association between serum vitamin D concentrations and TSH levels, leading to speculate that vitamin D deficiency in HT patients could be associated with a progression towards hypothyroidism (TSH > 5.0 m UI/L) [45]. Our study also demonstrates negative Correlation between Serum 25 hydroxy vitamin D (ng/mL) vs Serum TSH (mU/L) and the result was statistically significant. Pearson Correlation Coefficient (r) = -0.301, p value = 0.003. So, the results indicate that vitamin D deficiency is a risk factor of Hashimoto's thyroiditis. Mean (mean± s.d.) Serum anti TPO antibody (IU/ml) before intervention was 545.06± 230.82 and after cholecalciferol supplementation the mean value decreased to 378.6± 160.49. So, there is a 30.5% reduction in the mean value of anti TPO antibody level. Difference of mean Serum anti TPO antibody (IU/mL) was statistically significant (p < 0.0001). In the placebo group the mean Serum anti TPO antibody (IU/ml) (mean ± s.d.) of patients was 686.97± 290.19 and after 8 weeks of placebo the mean value was 573.1 ± 254.09. So, in the placebo group the reduction is only 16.5%. Difference of mean Serum anti TPO antibody (IU/ml) was statistically significant (p < 0.0001). Therefore, in line with the hypothesis. The 8 weeks randomized; double-blind, placebo-controlled clinical trial demonstrates a negative correlation between Serum 25 hydroxy vitamin D vs anti TPO antibody level. Treatment with 60,000 IU cholecalciferol weekly for 8 weeks, is associated with significant decrease in antithyroid antibody titers. It also improved serum TSH level compared with the placebo, i.e. supplementary treatment with cholecalciferol seems to have beneficial effects on AITD. However, large multicentre studies are needed to investigate the impact of vitamin D supplementary treatment on meaningful long-term clinical end points in AITD. References Dana L. Mincer; Ishwarlal Jialal. StatPearls [Internet]. Hashimoto Thyroiditis. Treasure Island (FL): StatPearls Publishing; 2020 Jan. Leung AKC, Leung AAC. Evaluation and management of the child with hypothyroidism. World J Pediatr 2019;15(2):124-134. Yuan J, Sun C, Jiang S, et al. The pevalence of thyroid disorders in patients with vitiligo: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2018;. Front Endocrinol (Lausanne). 2018; 9:803. Yoo WS, Chung HK. Recent advances in autoimmune thyroid diseases. Endocrinol Metab (Seoul) 2016;31(3):379-385. Ke W, Sun T, Zhang Y, et al. 25-Hydroxyvitamin D serum level in Hashimoto's thyroiditis, but not Graves' disease is relatively deficient. Endocr J 2017;64(6):581-587. Shin D, Kim KJ, Kim D, et al. Low serum vitamin D is associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei Med J 2014; 55:476-481. ElRawi HA, Ghanem NS, ElSayed, N.M.; et al. Study of vitamin D level and vitamin D receptor polymorphism in hypothyroid egyptian patients. J Thyroid Res 2019. Kim CY, Lee YJ, Choi J, et al. The association between low vitamin d status and autoimmune thyroid disease in korean premenopausal women: the 6th korea national health and nutrition examination survey, 2013-2014. Korean J Fam Med 2019;40:323-328. Chaudhary S, Dutta D, Kumar M, et al. Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: An open-labelled randomized controlled trial. Indian J Endocrinol Metab 2016;20:391-398. 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Topics: Adult; Autoimmunity; Cholecalciferol; Dietary Supplements; Female; Graves Disease; Hashimoto Disease; Humans; Hypothyroidism; Male; Nutrition Surveys; Prospective Studies; Randomized Controlled Trials as Topic; Receptors, Calcitriol; Thyroid Hormones; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine; Vitamin D; Vitamin D Deficiency; Young Adult