Vitamin D is recognized to be an essential element for bone metabolism and skeletal health; however, its deficiency can cause rickets in children as well as an increased propensity for osteoporosis [
Few past studies have reported the impact of vitamin D deficiency on autoimmune thyroid disease and demonstrated inconclusive results [
From June to December 2011, we recruited a total of 9,982 Chinese living in Gulou, Nanjing. The study was approved by the ethics committee of the First Affiliated Hospital of Nanjing Medical University. All patients provided informed consent and completed a standardized questionnaire. Blood samples were collected and stored at −80°C.
The present study used a subsample collected from September to November 2011 to detect serum 25-hydroxyvitamin D [25(OH)D] levels, thyroid function, and thyroid autoantibodies. Subjects with a history of thyroid disease, without complete informations or taking medications that affected their thyroid function, such as oral contraceptives, oestrogen, glucocorticoids and iodine, were excluded.
Further exclusion criteria included overt hypothyroidism (TSH > 5.29
Serum samples were collected from all 1,424 participants in the morning and all venous blood samples after an overnight fast. The serum samples were used to measure FT4, FT3, TSH, and 25(OH)D levels. Only 1,279 and 1,357 serum samples were used to measure thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), respectively. Serum 25(OH)D levels were assessed using an enzyme immunoassay (IDS, UK). Serum TSH, TPOAb, and TgAb levels were measured using a chemiluminescent immunoassay (AutoBio Co., Ltd., Zhengzhou, China). Euthyroidism was defined as the absence of hypo- or hyperthyroidism. Serum TPOAb of >40 IU/mL and/or TgAb of >110 IU/mL were considered autoantibody positivity. High TPOAb and TgAb titres were defined as arbitrary values greater than 200 IU/mL and 550 IU/mL (four times greater than the normal values), respectively. We set vitamin D insufficiency and deficiency at levels below 75 nmol/L (30 ng/mL) and 50 nmol/L (20 ng/mL), respectively. The presence of thyroid nodule(s) and size of the thyroid gland were determined by thyroid ultrasonography. The thyroid volume was estimated by multiplication of its thickness, width, length, and a corrective factor (0.479) [
Continuous variables are presented as means ± standard deviation for continuous normally distributed variables and median (interquartile range) for nonnormally distributed variables. Categorical variables are presented as percentage. The Kolmogorov-Smirnov method was used to test for normality. Differences between two groups for continuous and categorical variables were separately assessed using the Student’s
The clinical and laboratory characteristics of the included 1,424 subjects (863 females and 561 males; age, 41–78 years) are shown in Table
Clinical and laboratory characteristics of the participants.
Characteristics | Male ( |
Female ( |
Total ( |
---|---|---|---|
Age (years) | 59.22 ± 9.03 | 59.04 ± 8.20 | 59.11 ± 8.53 |
BMI (kg/m2) | 24.93 ± 3.38 | 24.66 ± 3.36 | 24.76 ± 3.37 |
Serum 25 (OH)D (nmol/L) | 47.50 (38.00–59.00) | 42.90 (35.15–53.11)* | 44.68 (36.20–55.30) |
Serum FT3 (pmol/L) | 4.34 (3.99–4.69) | 4.31 (3.98–4.72) | 4.32 (3.98–4.69) |
Serum FT4 (pmol/L) | 15.87 (13.10–18.03) | 15.81 (13.22–17.95) | 15.83 (13.18–17.97) |
Serum TSH ( |
2.06 (1.36–3.30) | 3.03 (1.89–4.60)* | 2.65 (1.62–4.10) |
Serum TPOAb (IU/mL) | 3.09 (1.07–11.08) | 4.18 (1.24–16.28) | 3.66 (1.15–14.34) |
Serum TgAb (IU/mL) | 10.08 (6.87–19.22) | 13.19 (7.90–35.66)* | 12.06 (7.31–27.00) |
Thyroid volume (mL) | 8.44 (6.82–10.06) | 7.24 (5.83–8.82) | 7.74 (6.16–9.40) |
Presence of thyroid nodule(s) ( |
174 (31.02%) | 339 (39.28%)* | 513 (36.03%) |
Current smokers ( |
252 (44.92%) | 16 (1.85%)* | 268 (18.82%) |
Based on a cutoff value of 75 nmol/L (30 ng/mL), the subjects were grouped into vitamin D insufficiency and vitamin D sufficiency. Differences between the clinical and laboratory characteristics between the two groups are shown in Table
Comparison of clinical and laboratory characteristics based on vitamin D insufficiency.
Vitamin D insufficiency (1368) | Nonvitamin D insufficiency (56) |
| |
---|---|---|---|
Age (years) | 59.07 ± 8.55 | 60.07 ± 8.11 | 0.371 |
Male sex ( |
529 (38.67%) | 32 (57.14%) | 0.006 |
BMI (kg/m2) | 24.79 ± 3.40 | 24.21 ± 2.50 | 0.106 |
Serum FT3 (pmol/L) | 4.39 (3.97–4.69) | 4.48 (4.18–4.75) | 0.094 |
Serum FT4 (pmol/L) | 15.51 (13.14–17.93) | 16.29 (14.01–18.79) | 0.092 |
Serum TSH ( |
3.42 (1.62–4.18) | 2.47 (1.54–3.24) | 0.000 |
Serum TgAb (IU/mL) | 84.26 (7.26–27.77) | 21.12 (8.38–22.40) | 0.000 |
Serum TPOAb (IU/mL) | 40.45 (1.17–14.33) | 16.77 (0.99–14.99) | 0.000 |
Thyroid volume (mL) | 8.43 (6.12–9.35) | 8.71 (6.53–10.62) | 0.476 |
Presence of thyroid nodule(s) ( |
495 (36.18%) | 18 (32.14%) | 0.537 |
Current smokers ( |
814 (59.50%) | 37 (66.07%) | 0.326 |
Determinants of positive serum thyroid antibodies.
Serum TgAb | Serum TPOAb | Serum TgAb and/or TPOAb | ||||
---|---|---|---|---|---|---|
Adjusted OR (95% CI) |
|
Adjusted OR (95% CI) |
|
Adjusted OR (95% CI) |
| |
Age (years) | 0.997 (0.974–1.022) | 0.838 | 1.007 (0.983–1.032) | 0.558 | 1.009 (0.987–1.030) | 0.431 |
Male sex | 2.738 (1.526–4.910) | 0.001 | 2.200 (1.267–3.821) | 0.005 | 2.524 (1.550–4.110) | 0.000 |
BMI (kg/m2) | 1.035 (0.974–1.099) | 0.266 | 1.040 (0.979–1.106) | 0.204 | 1.039 (0.984–1.097) | 0.166 |
Smoking status | 0.786 (0.368–1.676) | 0.532 | 1.308 (0.685–2.499) | 0.415 | 1.052 (0.578–1.916) | 0.868 |
Serum 25(OH)D (nmol/L) | 0.992 (0.979–1.004) | 0.188 | 0.999 (0.987–1.010) | 0.818 | 0.997 (0.986–1.009) | 0.660 |
With regard to the relationship between vitamin D status and serum TSH level, it was found that higher 25(OH)D levels were associated with lower TSH levels independent of age, FT3 and FT4 levels, TPOAb and TgAb titres, thyroid volume, the presence of thyroid nodule(s), and smoking status in males (Beta = −0.166,
Standardized regression coefficients of variables in relation to serum TSH according to gender.
Male (561) | Female (863) | |||
---|---|---|---|---|
Beta |
|
Beta |
| |
Age (years) | −0.012 | 0.836 | −0.023 | 0.647 |
Serum FT3 (pmol/L) | 0.069 | 0.244 | −0.043 | 0.399 |
Serum FT4 (pmol/L) | −0.040 | 0.501 | −0.066 | 0.201 |
Presence of TgAb (%) | 0.029 | 0.636 | 0.098 | 0.060 |
Presence of TPOAb (%) | −0.002 | 0.971 | 0.056 | 0.284 |
Thyroid volume (mL) | −0.152 | 0.009 | −0.056 | 0.262 |
Presence of thyroid nodule(s) (%) | −0.025 | 0.669 | −0.116 | 0.023 |
Current smokers ( |
−0.054 | 0.361 | −0.001 | 0.985 |
Serum 25(OH)D (nmol/L) | −0.166 | 0.004 | −0.001 | 0.983 |
To determine the probable interaction between vitamin D status and thyroid autoantibody positivity on serum TSH levels, further analyses were performed based on positive serum TPOAb, TgAb and TPOAb, and/or TgAb titres. The concentration of 25(OH)D was negatively correlated with serum TSH levels only in subjects with negative serum TPOAb, TgAb and TPOAb and/or TgAb titres (
Standardized regression coefficients of variables in relation to serum TSH in males with negative serum antibodies.
Serum TgAb | Serum TPOAb | Serum TgAb and/or TPOAb | ||||
---|---|---|---|---|---|---|
Beta |
|
Beta |
|
Beta |
| |
Age (years) | 0.024 | 0.686 | 0.019 | 0.749 | 0.006 | 0.921 |
Serum FT3 (pmol/L) | 0.030 | 0.593 | 0.092 | 0.122 | 0.074 | 0.228 |
Serum FT4 (pmol/L) | 0.020 | 0.726 | −0.037 | 0.535 | −0.028 | 0.648 |
Thyroid volume (mL) | −0.165 | 0.003 | −0.170 | 0.004 | −0.154 | 0.011 |
Presence of thyroid nodule(s) (%) | −0.035 | 0.532 | −0.020 | 0.736 | −0.024 | 0.696 |
Current smokers ( |
−0.064 | 0.264 | −0.060 | 0.313 | −0.067 | 0.277 |
Serum 25(OH)D (nmol/L) | −0.157 | 0.004 | −0.166 | 0.004 | −0.184 | 0.002 |
In the present study, we explored the probable interaction between vitamin D status and thyroid autoantibodies on serum TSH levels in middle-aged and elderly Chinese population with euthyroidism. This report is the first, to the best of our knowledge, to show that a higher circulating 25(OH)D level was associated with lower TSH levels only in males with negative serum thyroid autoantibody titres independent of thyroid hormone levels.
The result that high vitamin D status was associated with low circulating TSH levels remained unknown. We hypothesized that vitamin D may influence the thyrotrophs by acting on vitamin D receptors, which are widely distributed through distinct portions of the brain system [
Chailurkit et al. [
It is generally agreed that serum 25(OH)D levels of <75 nmol/L (30 ng/mL) should be considered as representative of vitamin D insufficiency, whereas serum 25(OH)D levels of <50 nmol/L (20 ng/mL) as an indicative of vitamin D deficiency [
There were a number of limitations to the present study. First, TSH receptor-stimulating antibodies were not measured. Second, our study focused on middle-aged and elderly individuals; therefore, the relationship between vitamin D status and serum TSH levels in younger individuals with negative serum thyroid autoantibodies remained unknown. Finally, because of the cross-sectional nature of the present study, the causative effect of vitamin D on serum TSH could not be readily determined.
There was a high prevalence of vitamin D insufficiency among healthy adults. This population-based study was the first, to the best of our knowledge, to report an association between vitamin D and serum TSH levels independent of thyroid hormone levels in middle-aged and elderly males with negative thyroid autoimmunity. Here, we demonstrated a link between vitamin D insufficiency and serum thyroid autoantibody levels; however, vitamin D status was not associated with positive thyroid autoantibody titres after controlling for age, gender, and smoking status. Therefore, further longitudinal studies are required to clarify the relationship between vitamin D and serum TSH levels, particularly in subjects with negative-serum thyroid autoantibody titres.
The authors declare that there is no conflict of interests regarding the publication of this paper.
Qingqing Zhang, Zhixiao Wang, and Min Sun contributed equally to this study.
The authors thank all the participants in this study. This work was supported by the grants from the Chinese Society of Endocrinology and the Project Funded by Jiangsu Provincial Special Program of Medical Science (BL2012026).