Autoimmune thyroid diseases such as Hashimoto's thyroiditis and GD are among the most common autoimmune disorders. The onset of these diseases occurs by lymphocytic penetration into the thyroid gland and the production of anti-thyroid antibodies. These lymphocytes produce antibodies that bind to thyroid TSH receptor. Vitamin D plays an important role in regulating the immune system and has an inhibitory effect on the specific immune system [16]. GD is also an autoimmune disorder in which autoantibodies bind to thyrotropin receptors (TSH-Rs), causing excessive production and secretion of thyroid hormones, independent of the thyrotropin feedback regulation [19]. It seems that vitamin D inhibits the production of anti-thyroid antibodies by binding to VDR and activating VDR-relate genes. The VDR gene polymorphism is associated with autoimmune thyroid disease (AITD) [17].
The association between serum vitamin D levels and autoimmune diseases has generally been accepted by researchers [18]. In the present case-control study, the level of 25OHD has been evaluated in hyperthyroid patients, and compared with control subjects. Anti-thyroid antibody (TPOAb), anti-thyroglobulin antibodies (TGAb), TSH, T3, and T4 were also measured. In our study there was a high incidence of vitamin D deficiency. Among the 187 subjects, 113 (60.42%) patients were suffering from vitamin D deficiency.
The results of the present research indicated that positive TPOAb and TGAb incidences were more frequent in patients with vitamin D deficiency, yet the differences were not statistically significant. In terms of serum levels, despite the lower median of TGAb and TPOAb serum levels in individuals with sufficient vitamin D level compared to those with vitamin D deficiency, no significant differences were observed. Apparently, determining the cut-off measurement of these autoantibodies plays a role in these differences [22]. Tehran thyroid study, in which the median of TPOAb level of individuals with positive titer was considered to be 177 (79-366), was used as a measurement reference in specifying the diagnostic levels in the present research [20]. Accordingly, the subjects enrolled in the research as TPOAb positive had a median equivalent to 269 (143-489). The difference between these two values can occur due to the following reasons :(1) In the present study, most patients were diagnosed with known thyroid diseases; however, in Tehran’s study population, only the families living in Tehran were included. Therefore, the higher median level of TPOAb was foresighted in our study. (2) The difference in the number of participants can be yet another reason. In Tehran study, as a cohort study, the number of subjects were higher, yet no study has ever determined the natural courses of TGAb level in Iranian subjects.
Kivity et al. [15], as a pioneer in this field, reported the relationship between the lower levels of vitamin D and autoimmune thyroid disease. They also demonstrated the role of vitamin D in the pathogenesis of autoimmune diseases through considering anti-thyroid antibodies. The meta-analysis of Xu et al. showed that the deficiency of vitamin D increased the risk of GD disease, which is in agreement with the present findings [23].
No relationship was observed between serum vitamin D levels and hyperthyroid disease (non-autoimmune hyperthyroid disease or GD), meaning there was no significant difference in vitamin D levels of GD, non-autoimmune thyroid disease patients and healthy subjects. However, vitamin D deficiency was more frequent in GD patients.
Thyroid autoantibodies existed for several years prior to the onset of thyroid disease [24]. Of course, thyroid antibodies can be positive in people without thyroid dysfunction [7]. In our study, in the control group, 20 (28.57%) and 2 (2.85%) patients were reported as positive TPOAb and TGAb, respectively. Since the incidence of positive TPOAb was very high, the comparison of the relationship between TPOAb and vitamin D was affected by high positive antibody titers in the control subjects. In the study of Kohno et al. [23], 6.4% of the subjects were positive for autoantibodies. Their age range, being 17 to 23 years, is different from the present research. TPOAb of healthy people does not hinder the activity of TPO enzymes. These findings suggest that the properties of anti-TPO antibodies can be different for patients with pathological conditions of the thyroid [25].
Chaudhary et al. used vitamin D supplements to treat routine autoimmune diseases and reported the reduction of TPOAb titer following the treatment. On the other hand, vitamin D levels in our study were not able to predict TPOAb levels. Such difference can be due to the fact that their study was on 100 patients with newly diagnosed ATID. Besides, no differentiation was considered between the types of patients with autoimmune hyperthyroid diseases [24]. On the other hand, Wang et al. showed the relationship between lower serum levels of vitamin D and the presence of TGAb[26]. They further observed that the relationship between TGAb and vitamin D was more potent in female subjects. Apparently, sex differences play a major role in determining the relationship between Vitamin D and thyroid diseases. In the present study, vitamin D levels were higher in male subjects, while females had higher levels of TSH. Goswami et al. reported a weak correlation between TPOAb titers and Vitamin D levels [27]. In the present study, no correlation was observed between these two variables.
According to Choi et al., in pre-menopause women, TPOAb positive subjects had a lower level of vitamin D comparisons with TPOAb negative group [16]; however, in our study no differences were observed. In addition to the fact that Choi et al. did not measure the level of TgAb, the difference between the results of our study and them could be due to the difference in gender and age distribution of patients.
According to our results, the increase in the levels of vitamin D in patients with GD can be associated with improved treatment outcomes such as increased TSH levels. Nonetheless, this relationship between vitamin D and TSH levels could be affected by patient's age. Qingqing et al. reported the relationship between high serum vitamin D level and the lower level of TSH in old men [28]. Contrary to our results, Colbay et al. [29] showed that vitamin D levels had a negative relationship with the serum TSH level and no correlation with thyroid antibodies. Chailurkit et al. reported the association between the higher level of vitamin D in younger people and the increase in TSH levels [30]. In a study by Barchetta [31], lower Vitamin D levels were associated with higher TSH levels. In the present study, the median of GD patients age was lower than the other two groups (Table 1), which is in accordance with the aforementioned studies in terms of age and the effect of vitamin D on thyroid function.
Review of recent research indicated that thyroid autoimmunity is the consequence of an interaction of inflammatory cytokines, the immune modulating effect of vitamin D, and thyrocyte reactions to environmental factors [32]. Also, as Ferrari et al.[33] stated in a review study, low sun exposure and dietary vitamin D intake as environmental factors can be associated with autoimmune thyroid disease. Women’s clothing in Islamic countries as Iran causing low sun exposure could be one of the vitamin D deficiency reasons but regarding the Tabrizi et al.[34] systematic review study, other environmental reasons such as dietary habits, lifestyle, and air pollution affecting the prevalence of vitamin D deficiency should be considered.
One of the limitations of the present study, which does not allow for a generalization of the results, is the small size of the research community. Based on Effraimidis et al. study, the onset of autoimmune thyroid disease is not related to a lower vitamin D level [35]. So, examining the role of vitamin D in the GD autoimmune hyperthyroidism patients and even non-autoimmune hyperthyroid disease patients in the long-term is further recommended. Although there was no relationship between the vitamin D levels and non-autoimmune hyperthyroid disease, our results showed that non-autoimmune hyperthyroid disease patients had a higher mean age. Higher ages and low TSH levels are related to osteoporosis [36]. There is a high risk of osteoporosis in non-autoimmune hyperthyroid disease patients, hence, analyzing vitamin D levels and prescribing vitamin D supplements are needed.