Low Vitamin D Status Is Associated With Increased Thyrotropin-Receptor Antibody Titer in Graves Disease

Hong Zhang, MD; Lingyun Liang, MB; Zhongjian Xie, MD


Endocr Pract. 2015;21(3):258-263. 

In This Article

Abstract and Introduction


Objective Vitamin D deficiency is reportedly linked to a variety of autoimmune diseases. However, the relationship between thyroid autoimmunity in Graves disease (GD) and vitamin D deficiency is unclear. The goal of this study was to determine whether increased thyroid hormone autoantibody titer is associated with vitamin D deficiency in GD patients.

Methods A total of 70 patients with GD and 70 matched control subjects were recruited to our study. The levels of 25-hydroxyvitamin D (25[OH]D), calcium, parathyroid hormone (PTH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyrotropin-receptor antibody (TRAb), thyroid-peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) in serum collected from these patients and controls were examined.

Results The level of 25(OH)D in serum from TRAbpositive GD patients was significantly lower than that in serum of healthy controls or TRAb-negative patients. However, compared with control subjects, the level of PTH in serum was increased in TRAb-positive GD patients. The rate of vitamin D deficiency (defined as serum 25[OH]D <50 nmol/L) in TRAb-positive GD patients was significantly higher than in healthy controls or TRAb-negative GD patients. The level of 25(OH)D in serum was inversely correlated with TRAb titer in serum of TRAb-positive GD patients. However, our results did not show a correlation between 25(OH)D level and the levels of TPOAb, TGAb, FT3, FT4, or TSH.

Conclusion Low vitamin D status is associated with increased TRAb titer in GD, suggesting a possible link between vitamin D status and increased thyroid autoimmunity in GD patients.


Vitamin D is a precursor of the hormone 1,25-dihydroxyvitamin D (1,25[OH]2D). Vitamin D can be obtained from intake of certain foods and produced in the skin after ultraviolet B exposure. Vitamin D is converted to its major circulating form, 25-hydroxyvitamin D (25[OH]D, in the liver. In the kidney, 25(OH)D is then converted to 1,25(OH)2D, which regulates calcium, phosphorus, and bone metabolism.

1,25(OH)2D is not only a major regulator of calcium metabolism, it also regulates cell growth and differentiation.[1] One of the nonclassical roles for vitamin D is its immunoregulatory function. Epidemiologic data suggest that vitamin D deficiency may be a risk factor for development of autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and type 1 diabetes.[2–5] In animal models, increased vitamin D intake has been shown to prevent the onset and/or development of type 1 diabetes.[6]

Graves disease (GD) is an autoimmune thyroid disease characterized by the activation of autoantibodies against the thyroid-stimulating hormone (TSH) receptor, leading to excessive thyroid hormone production. The etiology and pathogenesis of GD is unclear. The vitamin D receptor (VDR) has been identified in thyroid follicular cells in rats, and this observation suggests that 1,25(OH)2D has some function in the thyroid.[7] Moreover, it has been shown that the VDR and 1α-hydroxylase are expressed in papillary thyroid carcinoma and normal thyroid tissue,[8,9] suggesting local synthesis of 1,25(OH)2D in the thyroid. More recently, it was reported that patients with Hashimoto's thyroiditis, an autoimmune thyroid disease, have lower 25(OH)D levels in the blood.[10] However, whether a relationship exists between vitamin D and GD remains unknown. In the present study, we examined the vitamin D status of patients with GD and found that low vitamin D levels are associated with increased TSHreceptor antibody titer in GD.