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Low Serum Vitamin D Is Associated with Anti-Thyroid Peroxidase Antibody in Autoimmune Thyroiditis

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Low Serum Vitamin D Is Associated with Anti-Thyroid Peroxidase Antibody in Autoimmune Thyroiditis http://dx.doi.org/10.3349/ymj.2014.55.2.476 Original Article pISSN: 0513-5796, eISSN: 1976-2437 Yonsei Med J 55(2):476-481, 2014 Low Serum Vitamin D Is Associated with Anti-Thyroid Peroxidase Antibody in Autoimmune Thyroiditis Dong Yeob Shin,1 Kwang Joon Kim,1,2 Daham Kim,1 Sena Hwang,1 and Eun Jig Lee1 1Division of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul; 2Severance Executive Healthcare Clinic, Yonsei University Health System, Seoul, Korea. Received: May 7, 2013 Purpose: The association between autoimmune thyroid diseases (AITDs) and vita- Revised: July 16, 2013 min D deficiency is controversial. We aimed to evaluate the relationship between se- Accepted: July 17, 2013 rum 25-hydroxy-vitamin D3 [25(OH)D3] and anti-thyroid antibody levels. Materials Corresponding author: Dr. Eun Jig Lee, and Methods: 25(OH)D3, anti-thyroid antibodies, and thyroid function measured in Division of Endocrinology, 304 patients who visited the endocrinology clinic were analyzed. The patients were Department of Internal Medicine, Yonsei University College of Medicine, subgrouped into the AITDs or non-AITDs category according to the presence or ab- 50-1 Yonsei-ro, Seodaemun-gu, sence of anti-thyroid antibodies. The relationship between anti-thyroid peroxidase Seoul 120-752, Korea. antibody (TPOAb) and 25(OH)D3 was evaluated. Results: The patients with elevat- Tel: 82-2-2228-1983, Fax: 82-2-393-6884 ed anti-thyroid antibodies had lower levels of serum 25(OH)D3 than those who did E-mail: [email protected] not (12.6±5.5 ng/mL vs. 14.5±7.3 ng/mL, respectively, p<0.001). Importantly, after ∙ The authors have no financial conflicts of adjusting for age, sex, and body mass index, a negative correlation (r=-0.252, interest. p<0.001) was recognized between 25(OH)D3 and TPOAb levels in the AITDs group, but this correlation did not exist in the non-AITDs group (r=0.117, p=0.127). 25(OH)D3 level was confirmed as an independent factor after adjusting for co-fac- tors that may affect the presence of TPOAb in the AITDs group. Conclusion: 25(OH)D3 level is an independent factor affecting the presence of TPOAb in AITDs. The causal effect of 25(OH)D3 deficiency to AITDs is to be elucidated. Key Words: Vitamin D deficiency, anti-thyroid peroxidase antibody, autoimmune thyroiditis INTRODUCTION The discovery of vitamin D receptor in most tissues and cells in the human body has provided new insights into the function of vitamin D as a unique hormone.1 Many studies have shown that vitamin D can play a role in decreasing the risk of chronic illnesses, including autoimmune, infectious, and cardiovascular diseases.2-7 © Copyright: Furthermore, the role of vitamin D as an immune-modulator has been reported in Yonsei University College of Medicine 2014 recent years, and low levels of vitamin D have been observed in several autoim- This is an Open Access article distributed under the mune diseases, including autoimmune thyroid diseases (AITDs).8-10 It has been es- terms of the Creative Commons Attribution Non- Commercial License (http://creativecommons.org/ timated that more than 1 billion people worldwide have vitamin D deficiency {se- licenses/by-nc/3.0) which permits unrestricted non- commercial use, distribution, and reproduction in any rum 25-hydroxy-vitamin D3 [25(OH)D3] below 20 ng/mL} or insufficiency medium, provided the original work is properly cited. [25(OH)D3 of 21-29 ng/mL]. Elderly people as well as children and young adults 476 Yonsei Med J http://www.eymj.org Volume 55 Number 2 March 2014 Low 25(OH)D3 Is Associated with TPOAb in AITDs are potentially at high risk for vitamin D deficiency.1,11-14 bott Ireland Diagnostic Division, Lisnamuck, Longford, Furthermore, in South Korea, it is now a greater threat to the Co. Longford, Ireland). Serum levels of TSHRAb (normal younger generation, especially to those in the age of 20-29 range: 0-1.75 IU/L), and TPOAb (threshold value: 0-13.7 and in young adults.15 Females have an especially higher IU/mL) were measured by an electro-chemiluminescence prevalence of AITDs.16,17 Hence, we hypothesized that there immunoassay according to standard protocols (COBAS, may be an association between vitamin D levels and AITDs. Roche Diagnostics GmbH, Mannheim, Germany). A few studies have examined the relationship between vitamin D insufficiency or deficiency and prevalence of Vitamin D measurements AITDs in humans. However, whether a definite association Serum 25(OH)D3 levels were measured by a radioimmunoas- between these two conditions exists is still controversial. say kit (DiaSorin, Inc., Stillwater, MN, USA; normal range: One recent study showed that the prevalence of vitamin D 9.3-37.6 ng/mL). Quantitative determination of 25(OH)D3 deficiency is higher in patients with AITDs and that the was carried out by a direct, competitive chemiluminescence presence of anti-thyroid antibodies is significantly more immunoassay. Specifically, magnetic particles (solid phase) common in patients with vitamin D deficiency than in those were coated with a specific antibody to vitamin D, and vita- with higher vitamin D levels.8 In contrast, another study min D was linked to an isoluminol derivative. During the performed in India revealed a weak association between incubation, 25(OH)D3 was dissociated from its binding pro- low vitamin D levels and AITDs. To elucidate the correla- tein and competed with labeled vitamin D for binding sites tion between vitamin D and AITDs, we analyzed vitamin D on the antibody. After the incubation, the unbound material levels in thyroid disease patients and evaluated the relation- was removed with a wash cycle, the starter reagents were ship between anti-thyroid peroxidase antibody (TPOAb) added, and a flash chemiluminescent reaction was initiated. and serum vitamin D levels. The light signal was measured by an photomultiplier as rel- ative light units and was inversely proportional to the con- centration of 25(OH)D3 present in calibrators, controls, or MATERIALS AND METHODS samples. Subjects Ultrasonographic evaluation The medical records of Korean patients who visited the en- Ultrasonographic evaluation of the thyroid gland was per- docrinology out-patient clinic of Severance Hospital from formed with an HDI 3000 or HDI 5000 system (Philips March 2010 to June 2011 were reviewed. All patients under- Medical Systems, Bothell, WA, USA) or an Acuson Sequoia went a thyroid function test and ultrasonography initially for 512 system (Siemens Medical Solutions, Mountain View, the purpose of thyroid evaluation. Serum anti-thyroid anti- CA, USA). Three well-trained radiologists performed a re- bodies including TPOAb and thyroid stimulating hormone al-time sonographic exam and interpreted the results. Ultra- (TSH) receptor antibody (TSHRAb) representing Hashimo- sonographic features of diffuse thyroiditis were defined us- to’s thyroiditis and Graves’ disease respectively, and 25(OH) ing the generally accepted standards of diffuse parenchymal D3 were additionally measured in these patients at the first hypoechogenicity or a heterogeneous echogenic pattern of visit. The patients taking anti-thyroid drugs or under thyroid thyroid gland. hormone replacement therapy were excluded. Among these patients, 304 were enrolled and subgrouped into either the Statistical analysis AITDs or the non-AITDs category according to the presence Comparison of categorical variables between groups was or absence of anti-thyroid antibodies, regardless of thyroid performed using chi-square test and Fisher’s exact test (two- functional status. This retrospective study was approved by tailed), as appropriate. Continuous variables are expressed as our Institutional Review Board, and informed consent was mean±standard deviation. The Student’s t-test and Mann- not required. Whitney U test was used for comparison of mean values be- tween groups. Statistical comparisons between groups were Thyroid function test and anti-thyroid antibodies performed using the chi-square test. Spearman correlations Serum TSH, free T4, and T3 were measured by chemilumi- were used to examine relationships between the log-trans- nescent microparticle immunoassay (Architect System, Ab- formed TPOAb titer and age, body mass index (BMI), Yonsei Med J http://www.eymj.org Volume 55 Number 2 March 2014 477 Dong Yeob Shin, et al. 25(OH)D3 and other biochemical variables. Correlations tients with AITDs was significantly lower than in patients were reported as age- and BMI-adjusted. To examine the with non-AITDs (56.8% vs. 16.1%, 11.9% vs. 16.2%, differences in 25(OH)D3 and other biochemical parameters 12.6±5.5 ng/mL vs. 14.5±7.3 ng/mL, respectively, p<0.001). between patients with or without TPOAb, a regression mod- TPOAb and TSHRAb were also significantly higher in the el fit the presence of TPOAb as the dependent variable and AITDs group than in the non-AITDs group (298.5±336.7 25(OH)D3 as the independent variable. p-values <0.05 were IU/mL vs. 6.4±2.6 IU/mL, p<0.001 and 5.11±7.97 IU/L vs. considered statistically significant for all tests. All analyses 1.40±3.45 IU/L, p<0.001, respectively). were performed using IBM SPSS software ver. 18.0 (SPSS Inc., IBM company, New York, NY, USA). Correlation between serum TPOAb and 25(OH)D3 levels Table 2 shows the correlation between anti-thyroid antibodies RESULTS and 25(OH)D3. In the AITDs group, the TPOAb level was in- versely correlated with 25(OH)D3 (r=-0.252, p<0.001) but not 25(OH)D3 levels in AITDs compared to non-AITDs in the non-AITDs group (r=0.117, p=0.127). TSHRAb was Baseline characteristics of AITDs and non-AITDs patients not correlateed with 25(OH)D3 levels in either group.
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