Vitamin D & Thyroid Hormone Autoantibody in Graves Disease
In the present study, we found low serum vitamin D levels in TRAb-positive GD patients, suggesting that low vitamin D status is associated with autoimmunity in GD. However, our study did not reveal any association between the levels of FT3, FT4, and serum 25(OH)D, suggesting that vitamin D status is not associated with the function of the thyroid in GD.
Vitamin D deficiency has become a general, worldwide problem and is considered a risk factor for autoimmune diseases. Basic, genetic, and epidemiologic studies indicate a potential role of vitamin D in the prevention of autoimmune diseases. Yamashita et al found that female GD patients who underwent subtotal thyroidectomy had lower serum 25(OH)D levels. Vitamin D levels in patients with autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis and GD, are lower than in patients with non-AITDs, such as toxic nodular goiter. The rates of vitamin D deficiency in patients with AITD are higher than that in patients with non-AITDs. Yasuda et al have reported that vitamin D levels in female patients with GD are decreased and that the decrease in vitamin D levels is associated with an increase in thyroid volume. However, others have found no relationship between vitamin D level and AITD or genetic susceptibility in AITD. Our present study revealed an association between TRAb titer and vitamin D status in GD. Moreover, we observed a negative correlation between BMI and 25(OH)D level. The reason for this relationship is probably less physical activity and therefore reduced sun exposure in heavier individuals.
It is known that a hyperthyroid state is associated with an increase in bone turnover, thereby resulting in subtle hypercalcemia with consequently suppressed PTH. However, our present study found that PTH levels were higher in GD patients than in normal controls. The relatively high PTH levels in GD patients could possibly be due to the relatively low vitamin D status.
GD is an autoimmune thyroid disease. It is thought that GD is characterized by a dominant T cell infiltration of the thyroid gland. Th1-mediated inflammatory responses predominate in the early stage of GD, whereas Th2-mediated immunity may play a role in the later stage. It has been shown that vitamin D is an important immune modulator, regulating both Th1 and Th2 cells. Vitamin D is implicated in prevention and protection from chronic infections, cancer, and autoimmune diseases, as it regulates both innate and adaptive immunity but suppresses adaptive immunity (T and B lymphocyte functions). Therefore, vitamin D deficiency may act as an environmental trigger of autoimmune diseases. Misharin et al have shown that BALB/cJ mice fed a vitamin D–deficient diet are more likely to develop persistent hyperthyroidism following 3 immunizations with TSH-receptor as opposed to their countermates receiving an adequate vitamin D supply. We observed an inverse association between 25(OH)D level and TRAb titer in newly diagnosed TRAb-positive GD patients but not in TRAb-negative GD patients. Our results are discrepant from those of a recent study that did not show a significant inverse association between serum 25(OH)D levels and TRAb titers in TRAb-positive GD patients treated with antithyroid drugs. The discrepancy is possibly due to the use of antithyroid therapy in the study by Yasuda et al. The possibility is supported by the fact that TRAb titers are inhibited by antithyroid therapies.
Discussion
In the present study, we found low serum vitamin D levels in TRAb-positive GD patients, suggesting that low vitamin D status is associated with autoimmunity in GD. However, our study did not reveal any association between the levels of FT3, FT4, and serum 25(OH)D, suggesting that vitamin D status is not associated with the function of the thyroid in GD.
Vitamin D deficiency has become a general, worldwide problem and is considered a risk factor for autoimmune diseases. Basic, genetic, and epidemiologic studies indicate a potential role of vitamin D in the prevention of autoimmune diseases. Yamashita et al found that female GD patients who underwent subtotal thyroidectomy had lower serum 25(OH)D levels. Vitamin D levels in patients with autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis and GD, are lower than in patients with non-AITDs, such as toxic nodular goiter. The rates of vitamin D deficiency in patients with AITD are higher than that in patients with non-AITDs. Yasuda et al have reported that vitamin D levels in female patients with GD are decreased and that the decrease in vitamin D levels is associated with an increase in thyroid volume. However, others have found no relationship between vitamin D level and AITD or genetic susceptibility in AITD. Our present study revealed an association between TRAb titer and vitamin D status in GD. Moreover, we observed a negative correlation between BMI and 25(OH)D level. The reason for this relationship is probably less physical activity and therefore reduced sun exposure in heavier individuals.
It is known that a hyperthyroid state is associated with an increase in bone turnover, thereby resulting in subtle hypercalcemia with consequently suppressed PTH. However, our present study found that PTH levels were higher in GD patients than in normal controls. The relatively high PTH levels in GD patients could possibly be due to the relatively low vitamin D status.
GD is an autoimmune thyroid disease. It is thought that GD is characterized by a dominant T cell infiltration of the thyroid gland. Th1-mediated inflammatory responses predominate in the early stage of GD, whereas Th2-mediated immunity may play a role in the later stage. It has been shown that vitamin D is an important immune modulator, regulating both Th1 and Th2 cells. Vitamin D is implicated in prevention and protection from chronic infections, cancer, and autoimmune diseases, as it regulates both innate and adaptive immunity but suppresses adaptive immunity (T and B lymphocyte functions). Therefore, vitamin D deficiency may act as an environmental trigger of autoimmune diseases. Misharin et al have shown that BALB/cJ mice fed a vitamin D–deficient diet are more likely to develop persistent hyperthyroidism following 3 immunizations with TSH-receptor as opposed to their countermates receiving an adequate vitamin D supply. We observed an inverse association between 25(OH)D level and TRAb titer in newly diagnosed TRAb-positive GD patients but not in TRAb-negative GD patients. Our results are discrepant from those of a recent study that did not show a significant inverse association between serum 25(OH)D levels and TRAb titers in TRAb-positive GD patients treated with antithyroid drugs. The discrepancy is possibly due to the use of antithyroid therapy in the study by Yasuda et al. The possibility is supported by the fact that TRAb titers are inhibited by antithyroid therapies.
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