Skip to main content
Download PDF

A beneficial levels of 25-hydroxyvitamin D for a decrease in thyrotropin receptor antibody (TRAB) in patients with Graves’ disease: a real-world study

BMC Endocrine Disorders volume 25, Article number: 14 (2025) Cite this article

Abstract

Objective

This study aimed to determine whether a relationship exist between pre-therapy 25-hydroxyvitamin D levels and the remission/negative conversion rates of thyrotropin receptor antibody (TRAB) during treatment in patients with newly diagnosed Graves’ disease (GD).

Methods

171 patients were included from the Endocrinology Department of the First Affiliated Hospital of Fujian Medical University in March 2013 to April 2016. Ninety-five patients of them were diagnosed at our hospital but transferred to local hospitals for treatment. Seventy-six patients were followed and treated at our hospital with a median follow-up time of 11.03 (range 6–27) months. Patients were divided into 3 groups according to baseline 25-hydroxyvitamin D levels; <20 ng/mL (31,43.05%), 20–29 ng /mL (20,27.78%), and ≥ 30 ng/mL (20,29.17%). The TRAB remission rate and negative conversion rate was assessed among each group.

Results

There was a higher TSH and lower TRAB titer in the 20–29 ng/mL group at initial diagnosis. Cox regression analysis suggested that 20–29 ng/mL group had significantly higher remission rates [RR; 95% CI: 7.505 (1.401–40.201), 8.975 (2.759–29.196),6.853(2.206–21.285), respectively] and negative conversion rates [RR; 95% CI: 7.835 (1.468–41.804),7.189(1.393–37.092), 8.122(1.621–40.688)] at the 6-, 12-, and 24-month follow-up, respectively . The level of 25-hydroxyvitamin D at the time of initial diagnosis was not associated with the re-normal of free Triiodothyronine(FT3), free thyroxineIndex(FT4) or TSH levels during the follow-up.

Conclusion

Newly diagnosed GD patients with appropriate baseline 25-hydroxyvitamin D levels (20–29 ng/mL) are beneficial for the reduction of TRAB during antithyroid therapy.

Peer Review reports

Introduction

Graves’ disease (GD) is a thyroid disorder closely associated with autoimmunity. The thyroid-stimulating hormone receptor antibody (TRAb) plays a crucial role in the onset, progression, and prognosis of Graves’ disease [1, 2]. The TRAB is present in the serum of Graves’ disease patients, which is permanently activated during the state of autoimmunity, leading to a vicious cycle of thyroid dysfunction [3]. Medical treatment with antithyroid drugs (ATDs) is typically the first line of therapy. However, recurrence of hyperthyroidism after a 12–18-month course of ATDs occurs in approximately 50% of patients, indicating that the remission and recurrence rates associated with this approach are unsatisfactory [4]. Previous studies have indicated that TRAB levels, smoking status, lower TSH levels, thyroid size, Graves’ disease-associated ophthalmopathy, recent stress events, and lower levels of 25-hydroxyvitamin D are significant factors associated with the recurrence of Graves’ disease both before and after ATD treatment [5,6,7]. Vitamin D is a fat-soluble steroid that regulates bone metabolism and calcium and phosphorus homeostasis [8]. Studies have shown that vitamin D also influences the progression or outcome of a variety of extraosseous diseases. Vitamin D deficiency is associated with an increased risk of immune dysfunction such as inflammatory bowel disease and rheumatoid arthritis, tumors, cardiovascular disease, and glucose metabolism disorders [9,10,11]. Vitamin D combined supplementation may increase the early efficacy of MMI treatment, showing an add-on effect [12]. Serum 25-hydroxyvitamin D is the main indicator of vitamin D levels in the human body, and the nutritional status of vitamin D is assessed by measuring the concentration of 25-hydroxyvitamin D [13]. However, scanty and controversial data are available about vitamin D deficiency and Graves’ disease. Consequently, there is consensus that TRAB is pathogenic in GD, having predictive potential in GD remission and recurrence events [1, 2]. The aim of this study was to explore whether vitamin D levels can affect the outcome of TRAB in patients with Graves’ disease.

Materials and methods

Study subjects

Participant recruitment

A retrospective cohort study collected 171 patients newly diagnosed with GD at the Endocrinology Department of the First Affiliated Hospital of Fujian Medical University from March 2013 to April 2016. The GD diagnosis complied with the US Thyroid Association 2011 Guidelines [14]. Ninety-five patients were diagnosed at our hospital but transferred to local hospitals for treatment for their will. Seventy-six patients were regularly followed up at our hospital. Cases with loss of follow-up, discontinuation of medications, or side effects of drugs were not included in the present study. Among the 72 patients who were eligible for the analysis, there were 19 (26.39%) males and 53 (73.61%) females. The mean age was 41.93 ± 11.22 years old and the median follow-up time was 11.03 months (range 6–27 months). Exclusion criteria: recent infections, heart disease, liver malignancy, gravida, thyroidectomy, other endocrine diseases, and other autoimmune diseases, as well as medications that affect vitamin D status were excluded from the present study. The study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University, with the participants’ written informed consent. The detail of the participant recruitment is provided in Fig. 1.

Fig. 1
figure 1

Study design and patient disposition diagram

Full size image

Sample size determination

The sample size was determined for Cox Regression using the Power Analysis and Sample Size (PASS) software, version 15.0. The proportion of group 1 (< 20 ng/mL), group 2 (20–29 ng/mL), and group 3 (≥ 30 ng/mL) was assumed to be 10%, 35%, and 18% for TRAB Negative conversion based on the pilot study. The estimated sample size was 35. The sample size was determined for the different clinical outcome. The largest sample size among these clinical outcomes was taken. Allowing a nonresponse rate of 10%, the optimal sample size was 39.

Methods

Data collection

A detailed medical history, patients’ gender, age, height, weight, history of hypertension, history of diabetes, history of hyperthyroidism, history of smoking, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were recorded. Height and weight were measured by the patient in the morning after urinating, wearing light clothing, and standing barefoot on a balance machine. Body mass index (BMI) = weight (kg)/height 2 (m2). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was measured strictly after a 15-minute rest. Behavioral variables such as smoking, drinking, exercising, were defined as pre-study [15].

Laboratory measurements

All patients were fasted for more than 8 h and blood was subsequently collected. Levels of glycated hemoglobin (HbA1c) (Variant II glycated hemoglobin analyzer, Bio-Rad, high performance liquid chromatography), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and 2-h blood glucose (ADVIA 2400 automatic biochemical analyzer Siemens, Germany) were determined. Levels of thyroid hormones and autoantibodies were measured using a chemiluminescence immunoassay method: thyrotropin receptor antibody TRAB (0-1.75 Iu/L), free triiodothyronine (3.5–6.59 pmol/L), free thyroxine index (11.5–22.7 pmol/L), thyroid stimulating hormone (0.35–5.50 IU/mL), and anti-thyroid peroxidase TPOAb (0-60IU/mL). The serum 25-hydroxyvitamin D were evaluated using the Cobas E601 analyzer (Roche, Germany, electrochemiluminescence). All patients were classified into three groups according to serum 25(OH)D levels: group 1 (< 20 ng/mL), group 2 (20–29 ng/mL), and group 3 (≥ 30 ng/mL).

Thyroid-associated ophthalmopathy (TAO) and goiter grade

TAO was diagnosed according to the Bartley criteria [16], excluding patients with normal thyroid function and hypothyroidism and other local or systemic immune and inflammatory diseases, and those who used glucocorticoids or immunosuppressive agents within 3 months. Goiter: I degree: thyroid not visible in the neck, but can be detected by touch; II degree: an enlarged thyroid gland visible in the neck, the enlargement can be detected by palpation, and the outline of the thyroid gland does not exceed the sternocleidomastoid trailing edge; III degree: thyroid enlargement can be detected by palpation and the outline of thyroid exceeds the sternocleidomastoid trailing edge.

Clinical outcome

Negative conversion: TRAB was less than 1.75 IU/L; TRAB remission was defined as TRAB levels 50% less than the levels of pre-therapy or negative conversion during the follow-up period; FT3 re-normal: FT3 returned to the above normal range; FT4 re-normal: FT4 returned to the above normal range; FT3 and FT4 re-normal: both FT3 and FT4 returned to the above normal range; TSH re-normal: TSH returned to the above normal range.

Statistical analysis

Data are expressed as the mean ± standard deviation (SD) and median value with interquartile ranges (25th percentile-75th percentile) (IQR). Prevalence comparisons have been carried out using the Chi-square or Fisher’s exact test. Kaplan-Meier survival analysis was used to analyze the difference in prognosis among the groups; a COX proportional hazards regression model was used to analyze the difference in vitamin D levels and the risk of the above-mentioned clinical events. P < 0.05 is defined as statistically significant. Figure was done using GraphPad Prism 8.0.2 software (GraphPad Software Inc., San Diego, CA, USA). Statistical analyses were performed using the R software, version 4.3.0.

Results

Clinical features of the different 25-hydroxyvitamin D levels in newly diagnosed GD patients

In the study of 171 newly diagnosed GD patients, we observed significant differences in the proportions of males, smokers, and alcohol drinkers, as well as in TCH, HDL, and LDL levels across groups with varying 25-hydroxyvitamin D levels (p < 0.05). Specifically, compared to the group with 25-hydroxyvitamin D levels < 20 ng/mL, the 20–29 ng/mL group had a higher smoking rate and lower TRAB levels (p < 0.05), while there were no significant differences in the proportion of alcohol drinkers or in TCH, HDL, and LDL levels.

Additionally, the ≥ 30 ng/mL 25-hydroxyvitamin D group had a greater proportion of males and a higher prevalence of smokers and alcohol drinkers (p < 0.05), although there were no significant differences in TRAB, TCH, HDL, or LDL levels. When comparing the 20–29 ng/mL group to the ≥ 30 ng/mL group, the latter group also included more males and exhibited higher TRAB levels, along with lower TC, HDL, and LDL levels (p < 0.05); however, the proportions of smokers and alcohol drinkers did not significantly differ.

Furthermore, factors such as age, BMI, blood pressure, FT3, FT4, TSH, TPOAB, glucose, HbA1c, TG, exercise history, thyroid-associated ophthalmopathy, goiter grade, family history of hyperthyroidism, history of hypertension, history of diabetes, and the seasons during which vitamin D was measured showed no significant differences related to the levels of 25-hydroxyvitamin D, as summarized in Table 1.

Table 1 Clinical characteristics of newly diagnosed Graves’ disease (GD) patients
Full size table

Changes in FT3, FT4, TSH, and TRAB in the 72 GD patients with different levels of 25-hydroxyvitamin D

In the 72 patients with newly diagnosed GD who completed follow-up, we found that the group with 25-hydroxyvitamin D levels < 20 ng/mL had lower TSH levels and higher TRAB titers compared to the 20–29 ng/mL group at initial diagnosis (p < 0.05). Additionally, the ≥ 30 ng/mL 25-hydroxyvitamin D group exhibited the lowest FT3 levels at initial diagnosis, while the 20–29 ng/mL group had the lowest FT4 levels; however, these differences were not statistically significant (Fig. 2).

Fig. 2
figure 2

Changes in FT3, FT4, TSH, and TRAB in the 72 GD patients with different levels of 25-hydroxyvitamin D.*using a variance analysis, the pairwise relationships were studied using Least-Significant Difference (LSD) p < 0.05. #using a rank sum test, the pairwise relationships were studied using Nemenyi test p < 0.05

Full size image

Analysis of the relationship between 25-hydroxyvitamin D levels and TRAB remission and negative conversion rates, and thyroid function during follow-up

Kaplan-Meier survival analysis shows that compared with < 20 ng/mL group, the TRAB remission and negative conversion rates in the 20–29 ng/mL group began to significantly increase at the 6-month, and this increase remained at the 12- and 24-month follow-up. Moreover, the ≥ 30 ng/mL group had no difference in TRAB remission or negative conversion rates during the 24-month follow-up period. Compared with the 20–29 ng/mL group, the ≥ 30 ng/mL group showed a lower TRAB remission rate from the 12-month until the 24-month follow-up period, but the TRAB negative conversion rate was a non-significantly lower (Fig. 3). Furthermore, in Fig. 1, we used restricted cubic splines to flexibly model and visualize the relation of 25-hydroxyvitamin D levels with TRAB remission and negative conversion rates. The plot showed a non-linearity, but U-shaped relation between 25-hydroxyvitamin D levels with TRAB remission and negative conversion rates (Fig. 4). The model was adjusted for age, gender, season, and other factors. For another, there was no statistical difference in the recovery process of FT3, FT4, or FT3 and FT4 among the groups during the entire follow-up period. At the end of the follow-up period, TSH recovery in the 20–29 ng/mL group was higher than in the < 20 ng/mL group (Fig. S1).

Fig. 3
figure 3

Kaplan-Meier survival curve analysis of the relationship between different 25-hydroxyvitamin D levels and remission and negative conversion rates during follow-up

Full size image
Fig. 4
figure 4

Association of 25-hydroxyvitamin D levels with TRAB remission and negative conversion rates. Adjusted for age, gender, season, drugs using (Metamidazole, Propyrimethrin), Graves’ Disease family history, duration of Graves’ Disease

Full size image

COX regression analysis of the difference in the TRAB remission and negative conversion rates among the 25-hydroxy vitamin D levels during the follow-up period

COX regression analysis suggested that after adjustment for age, gender, season, and other factors, compared with the < 20 ng/mL 25-hydroxyvitamin D group, at the 6-, 12-, and 24-month follow-ups, the 20–29 ng/mL group had higher remission rates [RR; 95% CI: 7.505 (1.401–40.201), 8.975 (2.759–29.196),6.853(2.206–21.285), respectively] and higher negative conversion rates [RR; 95% CI: 7.835 (1.468–41.804),7.189(1.393–37.092),8.122(1.621–40.688), respectively] (Fig. 5). From the 6-month follow-up until the end of the natural follow-up period, there were no statistically significant differences in re-normal FT3, FT4, TSH, or FT3 and FT4 after ATD treatment among the different baseline 25-hydroxyvitamin D levels (Fig. S2).

Fig. 5
figure 5

COX regression analysis of the difference in the TRAB remission and negative conversion rates among the 25-hydroxy vitamin D levels during follow-up. Model1: Adjusted for age, gender, season; Model2: Model1 + drugs using (Metamidazole, Propyrimethrin), Graves’ Disease family history, duration of Graves’ Disease

Full size image

Discussion

In the present study, we observed differences in TRAB levels among newly diagnosed GD patients with varying 25-hydroxyvitamin D levels. Patients with appropriate baseline 25-hydroxyvitamin D levels exhibited lower TRAB titers and higher rates of TRAB remission and negative conversion during follow-up. Additionally, we identified a non-linear, U-shaped relationship between 25-hydroxyvitamin D levels and the rates of TRAB remission and negative conversion.

Vitamin D deficiency is an established risk factor for many autoimmune diseases and the anti-inflammatory properties of vitamin D underscore its potential therapeutic value for these diseases. The analysis demonstrated an inverse association between vitamin D and the development of several autoimmune diseases, such as systemic lupus erythematosus, thyrotoxicosis, type 1 DM, multiple sclerosis, iridocyclitis, Crohn’s disease, ulcerative colitis, psoriasis vulgaris, rheumatoid arthritis, polymyalgia rheumatica [17, 18]. Hower, scanty and controversial data are available about vitamin D deficiency and Graves’ disease and its prognosis. Our study demonstrated that newly diagnosed GD patients with appropriate 25-hydroxyvitamin D levels have lower TRAB titers. Autoimmunity plays an important role in the pathogenesis of GD. CD4 + and T2 helper (Th2) cells induce antibody binding to thyroid stimulating hormone (TSH) receptors, which initiates the growth of thyroid follicular cells and thyroid hormone secretion, leading to hyperthyroidism [19,20,21]. 25-hydroxyvitamin D is also involved in immune regulation and is associated with the pathogenesis of Graves’ disease [22,23,24]. Almost all immune cells express the vitamin D receptor (VDR), including T cells, B cells, and antigen-presenting cells [25, 26]. Vitamin D is converted to the active form, 25-hydroxyvitamin D, in vivo, and binds to the VDR, inhibiting B cell proliferation, plasma cell differentiation, immunoglobulin secretion, and memory B cell production; thereby, inhibiting B cell secretion of TRAB. Low levels of vitamin D are not conducive to the inhibition of B cell secretion of TRAB. A previous study observed that BALB/c mice fed a vitamin D-free diet had persistent hyperthyroidism, whereas mice fed a diet containing sufficient vitamin D did not develop this dysfunction [26]. Low vitamin D levels might hamper the anti-inflammatory immune response [12]. Other studies have found that TRAB-positive GD patients have lower vitamin D levels(GD patients 14.4 ± 4.9 ng/ml vs. Control subjects 17.1 ± 4.1 ng/ml ) [7]. Interestingly, a higher 25-hydroxyitamin D levels with more than 30 ng/ml did not cause great TRAB titer reductions in the present study, suggesting that an over replenishment vitamin D is not necessary. Substantial epidemiological studies have demonstrated that a 25-hydroxyitamin D level more than 30 ng/ml may have additional health benefits in reducing the risk of common cancers, autoimmune diseases, type 2 DM, cardiovascular disease, and infectious diseases [27]. However, scanty RCT have used an amount of vitamin D that raises the serum level above 30 ng/ml, and thus there remains appropriate skepticism about the potential noncalcemic benefits of vitamin D for health. Concern was also raised by the IOM report that some studies have suggested that all-cause mortality increased when serum levels of 25-hydroxyitamin D were greater than approximately 50 ng/ml [27]. Excessive levels of vitamin D may compromise this benefit. Consequently, maintain a blood level of 25-hydroxyitamin D above 20 ng/ml may be an acceptable level to prevent GD.

The present study found no correlation between 25-hydroxyitamin D levels and the return to normal levels of FT3, FT4, or TSH. This may account for ATD treatment leading to a rapidly alleviates and recovery of thyroid function, earlier than TRAB negative conversion [22,23,24].Greater thyroid volume has been identified as an independent risk factor for the recurrence of Graves’ disease [28]. The decrease in vitamin D levels in GD patients has been shown to be associated with an increase in thyroid volume [22]. A difference in thyroid volume was not found among the groups of GD patients with different vitamin D levels in the present study. A more possible explanation is that patients in present study were mostly with mild to moderate goiter, seldom with severe enlargement or compression symptoms, or need surgery or radioactive iodine treatment. Vitamin D metabolism can be affected by multiple environmental factors. such as effects of ultraviolet (UV) radiation [24, 29]. Thus, we also analyzed the seasonal differences in vitamin D determination. However, the present study did not reach such a conclusion.

Undoubtedly, the present study had several limitations. Firstly, the retrospective cohort performing in the hospital has the potential for selection bias. Secondly, the sample size was small, there was potential bias due to single-center analysis, and there was loss of follow-up data. Thirdly, there was no intervention for low-level baseline vitamin D patients, and future prospective studies are needed for verification. However, the strengths of the present study should also be demonstrated. Despite the shortcomings, we comprehensively assessed Graves’ Disease outcomes including thyroid function and immunological phenotypes associated with the vitamin D level, based on a Real-World Study. Patients were followed for more than two years.

Conclusion

The present study found that newly diagnosed GD patients with appropriate baseline 25-hydroxyvitamin D levels (20–29 ng/mL) had higher TRAB remission and negative conversion rates following ATD therapy, which may help to predict remission or negative conversion of TRAB, and in turn allow prediction of the prognosis of GD patients. However, this does not mean that vitamin D supplementation can increase the remission or negative conversion rates of TRAB following the treatment of hyperthyroidism or reduce the recurrence of GD in these cases.

Data availability

No datasets were generated or analysed during the current study.

References

  1. Suzuki N, Inoue K, Yoshimura R, Kinoshita A, Suzuki A, Fukushita M, et al. The mediation role of Thyrotropin receptor antibody in the relationship between age and severity of hyperthyroidism in Graves’ Disease. Thyroid: Official J Am Thyroid Association. 2022;32(10):1243–8.

    Google Scholar 

  2. Biscarini F, Masetti G, Muller I, Verhasselt HL, Covelli D, Colucci G, et al. Gut Microbiome Associated with Graves Disease and Graves Orbitopathy: the INDIGO Multicenter European Study. J Clin Endocrinol Metab. 2023;108(8):2065–77.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Okosieme OE, Taylor PN, Evans C, Thayer D, Chai A, Khan I, et al. Primary therapy of Graves’ disease and cardiovascular morbidity and mortality: a linked-record cohort study. Lancet Diabetes Endocrinol. 2019;7(4):278–87.

    Article  PubMed  Google Scholar 

  4. Wiersinga WM, Poppe KG, Effraimidis G. Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis. Lancet Diabetes Endocrinol. 2023;11(4):282–98.

    Article  PubMed  Google Scholar 

  5. Nedrebo BG, Holm PI, Uhlving S, Sorheim JI, Skeie S, Eide GE, et al. Predictors of outcome and comparison of different drug regimens for the prevention of relapse in patients with Graves’ disease. Eur J Endocrinol. 2002;147(5):583–9.

    Article  PubMed  Google Scholar 

  6. Vita R, Lapa D, Trimarchi F, Benvenga S. Stress triggers the onset and the recurrences of hyperthyroidism in patients with Graves’ disease. Endocrine. 2015;48(1):254–63.

    Article  PubMed  Google Scholar 

  7. Langenstein C, Schork D, Badenhoop K, Herrmann E. Relapse prediction in Graves disease: towards mathematical modeling of clinical, immune and genetic markers. Reviews Endocr Metabolic Disorders. 2016;17(4):571–81.

    Article  Google Scholar 

  8. Khairallah P, Nickolas TL. Bone and Mineral Disease in kidney transplant recipients. Clin J Am Soc Nephrology: CJASN. 2022;17(1):121–30.

    Article  Google Scholar 

  9. Nikiphorou E, Philippou E. Nutrition and its role in prevention and management of rheumatoid arthritis. Autoimmun rev. 2023;22(7):103333.

    Article  PubMed  Google Scholar 

  10. Dey SK, Kumar S, Rani D, Maurya SK, Banerjee P, Verma M, et al. Implications of vitamin D deficiency in systemic inflammation and cardiovascular health. Critical reviews in food science and nutrition 2024;64(28):10438–10455.

  11. Rebelos E, Tentolouris N, Jude E. The Role of Vitamin D in Health and Disease: a narrative review on the mechanisms linking vitamin D with Disease and the effects of Supplementation. Drugs. 2023;83(8):665–85.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Gallo D, Mortara L, Veronesi G, Cattaneo SA, Genoni A, Gallazzi M, et al. Add-On effect of selenium and Vitamin D combined supplementation in Early Control of Graves’ disease hyperthyroidism during Methimazole Treatment. Front Endocrinol. 2022;13:886451.

    Article  Google Scholar 

  13. Tripathi A, Ansari M, Dandekar P, Jain R. Analytical methods for 25-hydroxyvitamin D: advantages and limitations of the existing assays. J Nutr Biochem. 2022;109:109123.

    Article  PubMed  Google Scholar 

  14. Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid: Official J Am Thyroid Association. 2011;21(6):593–646.

    Article  Google Scholar 

  15. Lucas R, Fraga S, Ramos E, Barros H. Early initiation of smoking and alcohol drinking as a predictor of lower forearm bone mineral density in late adolescence: a cohort study in girls. PLoS ONE. 2012;7(10):e46940.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bartley GB, Gorman CA. Diagnostic criteria for Graves’ ophthalmopathy. Am J Ophthalmol. 1995;119(6):792–5.

    Article  PubMed  Google Scholar 

  17. Yamamoto E, Jørgensen TN. Immunological effects of vitamin D and their relations to autoimmunity. J Autoimmun. 2019;100:7–16.

    Article  PubMed  Google Scholar 

  18. Murdaca G, Tonacci A, Negrini S, Greco M, Borro M, Puppo F, et al. Emerging role of vitamin D in autoimmune diseases: an update on evidence and therapeutic implications. Autoimmun rev. 2019;18(9):102350.

    Article  PubMed  Google Scholar 

  19. Altieri B, Muscogiuri G, Barrea L, Mathieu C, Vallone CV, Mascitelli L, et al. Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept. Reviews Endocr Metabolic Disorders. 2017;18(3):335–46.

    Article  Google Scholar 

  20. Klecha AJ, Barreiro Arcos ML, Frick L, Genaro AM, Cremaschi G. Immune-endocrine interactions in autoimmune thyroid diseases. Neuroimmunomodulation. 2008;15(1):68–75.

    Article  PubMed  Google Scholar 

  21. Wang J, Lv S, Chen G, Gao C, He J, Zhong H, et al. Meta-analysis of the Association between Vitamin D and autoimmune thyroid disease. Nutrients. 2015;7(4):2485–98.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Yasuda T, Okamoto Y, Hamada N, Miyashita K, Takahara M, Sakamoto F, et al. Serum vitamin D levels are decreased and associated with thyroid volume in female patients with newly onset Graves’ disease. Endocrine. 2012;42(3):739–41.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Li X, Wang G, Lu Z, Chen M, Tan J, Fang X. Serum 25-hydroxyvitamin D predict prognosis in radioiodine therapy of Graves’ disease. J Endocrinol Investig. 2015;38(7):753–9.

    Article  Google Scholar 

  24. Zhang H, Liang L, Xie Z. Low vitamin D status is Associated with increased thyrotropin-receptor antibody titer in Graves Disease. Endocr Practice: Official J Am Coll Endocrinol Am Association Clin Endocrinologists. 2015;21(3):258–63.

    Article  Google Scholar 

  25. Peelen E, Knippenberg S, Muris AH, Thewissen M, Smolders J, Tervaert JW, et al. Effects of vitamin D on the peripheral adaptive immune system: a review. Autoimmun rev. 2011;10(12):733–43.

    Article  PubMed  Google Scholar 

  26. Misharin A, Hewison M, Chen CR, Lagishetty V, Aliesky HA, Mizutori Y, et al. Vitamin D deficiency modulates Graves’ hyperthyroidism induced in BALB/c mice by thyrotropin receptor immunization. Endocrinology. 2009;150(2):1051–60.

    Article  PubMed  Google Scholar 

  27. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30.

    Article  PubMed  Google Scholar 

  28. Ahn HY, Chung YJ, Cho BY. Serum 25-hydroxyvitamin D might be an independent prognostic factor for Graves disease recurrence. Medicine. 2017;96(31):e7700.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Zhang H, Zhu A, Liu L, Zeng Y, Liu R, Ma Z, et al. Assessing the effects of ultraviolet radiation, residential greenness and air pollution on vitamin D levels: a longitudinal cohort study in China. Environ Int. 2022;169:107523.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to the patients for their help and willingness to participate in the study.

Funding

This work was financially supported Scientific and Technological Major Special Project of Fujian Provincial Health Commission (No.2021ZD01004) and Foreign Cooperation Project of Fujian Science and Technology Planning Project (2022I1001).

Author information

Author notes

  1. Xide Chen, Yongze Zhang and Luxi Lin are co-first authors.

Authors and Affiliations

  1. Department of Endocrinology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China

    Xide Chen, Yongze Zhang, Luxi Lin, Yuxia Chen, Ximei Shen, Lingning Huang, Fengying Zhao & Sunjie Yan

  2. Department of Endocrinology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, China

    Xide Chen, Yongze Zhang, Luxi Lin, Yuxia Chen, Ximei Shen, Lingning Huang & Fengying Zhao

  3. Clinical Research Center for Metabolic Diseases of Fujian Province, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China

    Xide Chen, Yongze Zhang, Luxi Lin, Yuxia Chen, Ximei Shen, Lingning Huang & Fengying Zhao

  4. Fujian Key Laboratory of Glycolipid and Bone Mineral Metabolism, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China

    Xide Chen, Yongze Zhang, Luxi Lin, Yuxia Chen, Ximei Shen, Lingning Huang & Fengying Zhao

  5. Diabetes Research Institute of Fujian Province, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China

    Xide Chen, Yongze Zhang, Luxi Lin, Yuxia Chen, Ximei Shen, Lingning Huang & Fengying Zhao

  6. Metabolic Diseases Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China

    Xide Chen, Yongze Zhang, Luxi Lin, Yuxia Chen, Ximei Shen, Lingning Huang & Fengying Zhao

Authors
  1. Xide Chen
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Yongze Zhang
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Luxi Lin
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Yuxia Chen
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Ximei Shen
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Lingning Huang
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Fengying Zhao
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Sunjie Yan
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

Xide Chen and Yongze Zhang collected the clinical data from the patients, and wrote the manuscript. Luxi Lin and Yuxia Chen analyzed the data and contributed to the data collection. Fengying Zhao contributed to blood sample collection. Ximei Shen and Lingning Huang contributed to the review of the manuscript. Sunjie Yan contributed to the conception and design of the research, and acquisition and interpretation of the data, and revised the manuscript. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Sunjie Yan.

Ethics declarations

Ethics approval and consent to participate

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).

Informed consent

Was obtained from all patients for being included in the study. This study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University, and the participants gave informed consent and consent for publication.

Clinical trial number

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary Material 2

Supplementary Material 3

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, X., Zhang, Y., Lin, L. et al. A beneficial levels of 25-hydroxyvitamin D for a decrease in thyrotropin receptor antibody (TRAB) in patients with Graves’ disease: a real-world study. BMC Endocr Disord 25, 14 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12902-024-01823-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12902-024-01823-x

Keywords

BMC Endocrine Disorders

ISSN: 1472-6823

Contact us