Vitamin D deficiency and its association with thyroid peroxidase antibodies positive hypothyroidism - Experience in a tertiary center in South India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/MJDRDYPU.MJDRDYPU_252_16
Introduction: Vitamin D deficiency is one of the major health problems globally, and the role of Vitamin D as an immunomodulator has been recently emphasized. There is increasing evidence to suggest that Vitamin D plays a significant role in reducing the incidence of autoimmune diseases. However, at present, its role in autoimmune thyroid disease is not conclusive. Hence, in our study, we aimed to examine the relationship between thyroid peroxidase antibodies (TPOAbs) and Vitamin D deficiency in the hypothyroid patient. Subjects and Methods: One hundred and four known hypothyroid patients not on Vitamin D supplementation were included in the study. They were divided into two groups with TPOAb positive and TPOAb negative, and serum 25(OH) Vitamin D3 (25[OH] D3) was measured and compared in two groups. Thyroid hormones (TSH and T4) were also evaluated in all patients. Results: Serum 25(OH)D3 was significantly lower in TPOAb-positive patients than in TPOAb-negative patients with P = 0.038. Mean serum TSH was significantly high in TPOAb-positive hypothyroid patients than in TPOAb-negative patients with P = 0.047. Conclusion: Our study shows that patients with TPOAb positivity have more significant 25(OH)D3 deficiency and uncontrolled hypothyroidism. Our study encourages the advisability of screening for Vitamin D deficiency for all hypothyroid patients and 25(OH)D3 supplementation. Keywords: 25(OH) Vitamin D3, hypothyroidism, thyroid peroxidase antibodies
Vitamin D deficiency is one of the major health problems globally. Prevalence of Vitamin D deficiency or insufficiency is over a billion worldwide.[1] The role of Vitamin D has been evolving since the time of its discovery in the early 20th century from being a simple vitamin to a steroid prohormone.[2] Vitamin D has been recognized to be involved in various immune functions as well as bone and muscle development. Vitamin D deficiency has been shown to be associated with autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, and Type 1 diabetes, and that Vitamin D supplementation prevents the onset and/or development of these autoimmune diseases.[3] Furthermore, it was reported by Tamer et al. in 2011 that patients with Hashimoto's thyroiditis, an autoimmune thyroid disease, had lower Vitamin D levels.[4] Serum 25(OH)D3, the most abundant circulating precursor of active Vitamin D, is the most reliable and widely accepted indicator of Vitamin D status. Vitamin D deficiency is defined as a 25(OH)D3 below 20 ng/ml and Vitamin D insufficiency as 25(OH)D3 of 21–29 ng/ml. Levels of 25(OH)D3 >30 ng/ml are considered to be optimal.[5] Vitamin D and thyroid hormone have common receptors and bind to steroid hormone receptors. A gene in the Vitamin D receptor (VDR) has shown to predispose people to autoimmune thyroid disease including Graves' disease and Hashimoto's thyroiditis. Hence, it is important for patients with thyroid diseases to understand how Vitamin D system works. Vitamin D binds to VDR and mediates its effect, and VDR gene polymorphism has been found to be associated with autoimmune thyroid diseases.[6] Few studies were conducted to find any significant association between the levels of Vitamin D and hypothyroidism and it's pathogenesis but yielded conflicting results. Kivity et al. in 2011 documented significantly low levels of 25(OH)D3 with autoimmune thyroid disease, whereas a study by Goswami et al. showed a weak association between 25(OH)D3 levels and thyroid peroxidase antibody (TPOAb) titers.[7],[8] Thus, the purpose of our study was to examine and clarify the relationship between Vitamin D deficiency and TPOAb positivity hypothyroidism and also to estimate overall Vitamin D deficiency in hypothyroid patients.
One hundred and four hypothyroid patients were included in this study, who attended the endocrine outpatient department of Krishna Institute of Medical Sciences. The inclusion criteria for enrollment in the study included the following: (1) adult patients with a known case of hypothyroidism on treatment, (2) not on Vitamin D supplements, and (3) willing to participate in the study. Exclusion criteria included (1) very sick patient, (2) temporary hypothyroidism such as drug induced, in pregnant women, and (3) not willing for participation in the study. The patients who met the inclusion criteria were included, and history pertaining to hypothyroidism and management modalities was taken. The laboratory parameters that were assessed included thyroid function test (thyroid-stimulating hormone [TSH] and Free T4), TPOAb, and serum 25(OH)D3. They were divided into two groups: Group I - “anti-TPO-positive hypothyroid patients and Group II - “anti-TPO-negative hypothyroid patients and assessed and compared for 25(OH)D3 deficiency and also compared with general population from current literature to date.
A total number of patients included in the study were 104. As can be seen in [Table 1], significantly higher number of female patients with TPOAb positive hypothyroidism had a higher body mass index (28.22 ± 5.56 kg/m 2) than TPOAb-negative hypothyroid females (26.23 ± 7.75 kg/m 2) (P = 0.063). Whether the obesity has a bearing on TPOAb positivity is not known.
The duration of hypothyroidism was found to be longer in patients with TPOAb negative hypothyroidism, especially females (14.6 ± 18.21) (P = 0.096). Vitamin D levels were found to be significantly lower in TPOAb-positive hypothyroid patients (both male and female) (10.66 ± 18.34 ng/dL) as compared with TPOAb-negative patients (18.32 ± 24.89 ng/dL) (P = 0.038). Serum TSH was higher in TPOAb-positive hypothyroid females as compared to TPOAb-negative hypothyroid female patients (13.67 ± 74.56 vs. 10.67 ± 56.27) (P = 0.034). As seen in [Table 2], significantly higher number of female patients with TPOAb positive hypothyroidism had Vitamin D deficiency as compared with TPOAb-negative female patients (23 vs. 15) (P = 0.01). However, a significant difference in a number of male patients with TPOAb positive hypothyroidism and TPOAb negative hypothyroidism having vitamin deficiency on subgroup analysis was not seen (4 vs. 3) (P = 0.71). Whether deficiency of Vitamin D adds to the autoimmune phenomenon already more common in females, needs to be determined.
Even though as shown in [Table 1], mean serum TSH was higher in TPOAb-positive hypothyroid females as compared to TPOAb-negative hypothyroid female patients. This difference was not seen in male hypothyroid patients on subgrouping the TSH levels.
Vitamin D was known for its primary role in bone and mineral homeostasis, but recently, it has been shown that its deficiency is associated with various diseases such as cardiovascular disease, cancer, infection, and adiposity.[9] Interestingly, Vitamin D recently has shown potent immunomodulatory effects and plays important roles in the pathogenesis of autoimmune diseases.[4] Prevalence of 25(OH)D3 estimated in urban population was 62% in males and 75% in females, whereas the prevalence of Vitamin D deficiency was slightly lower in a rural area at 44% in males and 70% in females.[10] In South India, Harinarayan et al. in 2004 estimated Vitamin D deficiency in 69.3% of general population (58.6% in rural population and 85.6% in urban population).[11] Hence, the prevalence of Vitamin D deficiency was high in hypothyroid patients in our study when compared to general Indian population as described in earlier studies. This may be due to the effect of 25(OH)D3 on thyroid as reported by Byron Richards in his study that a lack of Vitamin D contributed to the possibility of low thyroid hormones.[3] Two mechanisms that may explain the low levels of Vitamin D in patients with hypothyroidism are: first, may be due to poor absorption of Vitamin D from the intestine and second, the body may not be able to activate Vitamin D properly.[3] In our study, we found that serum TSH was significantly higher in TPOAb-positive than TPOAb-negative hypothyroid patients. However, a study Shin et al. in 2013 did not find any significant difference. This could be due to a different sample population.[12] In our study, 25(OH)D3 levels were significantly lower in TPOAb-positive than TPOAb-negative hypothyroid patients. This was in keeping with various previous studies as described in meta-analysis by Wang et al.[13] In our study, we found the prevalence of 25(OH)D3 deficiency (<20 ng/dl) was significantly higher in TPOAb-positive than TPOAb-negative hypothyroid patient which was also shown by Shin et al. in 2014[12] and Kivity et al. in 2011.[7] Our study included the patients who visited our tertiary care hospital from which our population was sampled. Antithyroglobulin antibody and thyroglobulin levels were not measured because of cost constraints. However, these limitations might not affect the relationship between TPOAb and Vitamin D levels established in our study.
Our study shows the prevalence of Vitamin D deficiency is higher in hypothyroid patients when compared to general population. Our study also clearly found that 25(OH)D3 was significantly low in TPOAb-positive patients as compared to TPOAb-negative patients suggesting that the low 25(OH)D3 level is a possible risk factor of TPOAb positivity and vice versa. The effects of low Vitamin D level on anti-TPO positivity and whether Vitamin D replacement is helpful to the hypothyroid patients still require future validation, but as Vitamin D treatment is inexpensive and has minimal side effects, Vitamin D supplementation can be recommended in TPOAb-positive hypothyroid patients. Acknowledgment We would like to acknowledge Dr. Jalaj Khare, for helping in statistical analysis. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
[Table 1], [Table 2]
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