|Year : 2020 | Volume
| Issue : 3 | Page : 141-145
Pattern of Vitamin D deficiency in Hashimoto's thyroiditis and its association with thyroid hormone
Nazma Akter1, Tangera Akter2
1 Department of Medicine, MARKS Medical College and Hospital, Dhaka, Bangladesh
2 Department of Surgical Oncology, Delta Hospital Limited, Dhaka, Bangladesh
|Date of Submission||04-Oct-2020|
|Date of Acceptance||14-Dec-2020|
|Date of Web Publication||20-Jan-2021|
Dr. Nazma Akter
Department of Medicine, MARKS Medical College and Hospital, Dhaka
Source of Support: None, Conflict of Interest: None
Objective: The role of Vitamin D as an immune modulator has been recently emphasized. However, at this time, the research on its role in autoimmune thyroid disease is not conclusive. The purpose of this study was to examine the association of Hashimoto's thyroiditis (HT) and Vitamin D deficiency and to clarify the correlation between Vitamin D levels with thyroid hormone in patients with HT.
Methodology: In this cross-sectional study, hypothyroid HT patients were selected among referents to the endocrinology outpatient clinic of MARKS Medical College and Hospital, Dhaka, Bangladesh, for thyroid evaluation from January 2019 to March 2020. A total of 150 patients were enrolled and placed in the newly diagnosed hypothyroid HT “case group,” and a “control group” included 145 apparently healthy individuals (matched for age and gender). All the patients underwent thyroid function tests and serum 25-hydroxyvitamin D (25(OH)D) levels. The antibodies of interest were thyroid peroxidase antibody and thyroglobulin antibody, suggesting HT cases. Data were analyzed using SPSS version 18 statistical software.
Results: In this study, Vitamin D deficiency was prevalent in 32.2% of the “HT group” and 1.0% of the “control group” (P < 0.001). The Vitamin D-deficient participants had a significantly higher thyroid-stimulating hormone (TSH) and lower free thyroxine (FT4) level than the Vitamin D insufficient participants (TSH: 18.58 ± 8.73 vs. 8.52 ± 9.61 [μIU/mL], t = −7.816, P < 0.001; FT4: 0.81 ± 0.15 vs. 1.12 ± 0.17 [ng/dL], t = 13.36, P < 0.001, respectively). Concerning the HT case group, there was a significant negative correlation between serum 25(OH) Vitamin D and TSH (r = −0.178, P < 0.05). On the other hand, a significant positive correlation was recorded between serum 25(OH)D and serum FT4 levels (r = 0.610, P < 0.001).
Conclusions: Patients with HT present with a reduced serum 25(OH)D level, and low serum Vitamin D levels were independently associated with high serum TSH levels and low serum FT4 levels in those with subnormal levels of Vitamin D. TSH is negatively correlated with 25(OH)D level. On the other hand, FT4 levels are positively correlated with 25(OH)D levels.
Keywords: 25-Hydroxyvitamin D, Hashimoto's thyroiditis, thyroid-stimulating hormone, thyroxine
|How to cite this article:|
Akter N, Akter T. Pattern of Vitamin D deficiency in Hashimoto's thyroiditis and its association with thyroid hormone. Thyroid Res Pract 2020;17:141-5
|How to cite this URL:|
Akter N, Akter T. Pattern of Vitamin D deficiency in Hashimoto's thyroiditis and its association with thyroid hormone. Thyroid Res Pract [serial online] 2020 [cited 2021 Mar 6];17:141-5. Available from: https://www.thetrp.net/text.asp?2020/17/3/141/307559
| Introduction|| |
Vitamin D deficiency is a global health problem. Yet, no international health organization or governmental body has declared a health emergency to warn the public about the urgent need of achieving sufficient Vitamin D blood levels. Over a billion people worldwide are Vitamin D deficient or insufficient.
Vitamin D receptors (VDRs) exist in many body organs. Through these receptors, Vitamin D has various functions, including the regulation of ion homeostasis, cell growth, cell differentiation, and cellular immunity. Plenty of evidence has shown the role of Vitamin D in the regulation of pro-inflammatory cytokines, regulatory T-cells, and immune response. The main role of Vitamin D is to control bone metabolism and calcium and phosphorus homeostasis. Vitamin D is also associated with nonskeletal roles, including those found in autoimmune diseases, infectious diseases, metabolic syndrome and its components, cardiovascular diseases, cancers, and all-cause mortality.
The serum circulating 25-hydroxyvitamin D (25(OH)D) level is used to evaluate Vitamin D status in patients at risk for Vitamin D deficiency. Levels of 25(OH)D concentration below 20 ng/ml indicate Vitamin D deficiency, whereas a concentration of 20–30 ng/ml is considered insufficient, and a 25(OH)D level of 30–100 ng/ml defines Vitamin D sufficiency. Epidemiological studies have indicated a significant association between decreased levels of serum 25(OH)D and increased incidence of several autoimmune diseases including type 1 diabetes mellitus, rheumatoid arthritis (RA), systemic lupus erythematosus, multiple sclerosis, and inflammatory bowel disease, while experimental data have shown that Vitamin D supplementation can prevent or suppress these autoimmune diseases.,
The thyroid gland is also one of the organs that have a receptor for Vitamin D. The VDR in the thyroid is a member of a large group of receptors called nuclear receptors, which also belong to the thyroid hormone receptor. Furthermore, it was reported that patients with Hashimoto's thyroiditis (HT), an autoimmune thyroid disease (AITD), had lower Vitamin D levels. Importantly, both Vitamin D and thyroid hormone bind to similar receptors called steroid hormone receptors. A different gene in the VDR was shown to predispose people to AITD. Vitamin D mediates its effect through binding to VDR and activation of VDR-responsive genes, while VDR gene polymorphism was found to associate with AITDs.
Several studies have examined the relationship between low Vitamin D levels and the prevalence of AITD or HT in humans, but the results have been conflicting., Some studies have revealed low serum 25(OH)D levels in patients with AITD, as Vitamin D deficiency is correlated with the presence or high levels of antithyroid antibodies, abnormal thyroid function, increased thyroid volume, and increased thyroid-stimulating hormone (TSH) levels.,, Considering the potential role of Vitamin D in autoimmune diseases, the aim of this study is to evaluate the Vitamin D level in hypothyroid HT patients and to clarify the correlation between Vitamin D levels with thyroid function.
| Methodology|| |
In this cross-sectional study, hypothyroid HT patients were selected among referents to the endocrinology outpatient clinic of MARKS Medical College and Hospital, Dhaka, Bangladesh, for thyroid evaluation from January 2019 to March 2020.
Diagnosis criteria for hypothyroid HT included decreased free thyroxine (FT4) value (reference range: 0.71–1.85 ng/dL) along with an elevated TSH (reference range: 0.47–5.01 μIU/mL) and the presence of high serum thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TGAb) concentrations. The diagnosis of HT was based on the laboratory test findings: anti-TPOAb levels >35 IU/mL and/or anti-TgAb levels >40 IU/mL.
Study subjects and eligibility criteria
Participants underwent laboratory investigations of thyroid function tests and serum 25(OH)D levels. The antibodies of interest were TPOAb and TgAb, suggesting HT.
Participants who had transient thyroid dysfunction and negative thyroid autoantibodies, such as subacute thyroiditis or nonthyroidal illness, were not included. Patients aged <18 or >70 years, patients with type 1 diabetes, lupus, collagen vascular disease, RA, celiac disease, metabolic bone diseases, primary hyperparathyroidism, renal disorders, liver disorders, or epilepsy treated by anticonvulsants, or patients who underwent Vitamin D supplementation and Vitamin D metabolism interacting medications (such as antacids, corticosteroids, orlistat, diabetes medications, antihypertensive drugs, cholestyramine, and calcium supplements) were excluded from the study.
Finally, a total of 150 patients were enrolled using nonprobability type of purposive sampling and placed in the newly diagnosed hypothyroid HT “case group,” and a “control group” included 145 apparently healthy individuals (matched for age and gender) who were not complaining from any chronic medical diseases with normal clinical examinations, no history of thyroid diseases or any chronic illness may interfere with our results, and were not on Vitamin D or calcium supplements.
The study was approved by the Institutional Review Board of MARKS Medical Hospital. After taking consent from the individuals fulfilling the inclusion criteria of the study, a predesigned structured questionnaire was administered and filled by the doctor attending the patient. The detailed history of all such patients was taken, and a physical and relevant clinical examination was performed.
Clinical and laboratory assessments
Height and body weight were measured using a digital scale, and body mass index (BMI) was calculated as body weight (kg)/height squared (m2). Systolic blood pressure and diastolic blood pressure were measured after15-min rest.
The blood sample for laboratory tests was drawn from individuals after 8 h or more of fasting, and tests included the following: serum TSH, FT4, TPOAb, and anti-TgAb were quantified using VITROS ECI immunoassay system. Serum 25(OH)D concentration was measured using an auto Beckman coulter chemical analyzer AU480.
All analyses were performed using SPSS software version 18.0 (SPSS, Chicago, IL, USA). A comparison of categorical variables between the groups was done using the Chi-square test. Continuous variables are expressed as mean ± standard deviation (SD). The independent samples t-test and ANOVA were used for comparison of continuous variables between two and more groups, respectively. Pearson's correlation analysis was performed to examine the correlation between Vitamin D and biochemical variables. All P values were two-sided, and P < 0.05 was considered statistically significant for all tests.
| Results|| |
Clinical and laboratory characteristics of different groups
A total of 295 participants (178 females and 117 males) were enrolled. The mean (±SD) age was 42.50 ± 8.91 years, and the mean (±SD) BMI was 26.84 (±3.54) kg/m2. They were classified into “case group” including 150 hypothyroid HT patients (male: 61 [20.7%] and female: 89 [30.2%]) and “control group” including 145 apparently healthy individuals (male: 56 [19.0%] and female: 89 [30.2%]).
The mean values (±SD) of all studied clinical and biochemical parameters and age and sex distribution in all the studied groups are shown in [Table 1]. There were no statistical difference between the groups regarding age (P = 0.15), sex (P = 0.72), and BMI (P = 0.58). The mean (±SD) TSH levels were 18.26 (±8.38) versus 2.34 (±0.83) μIU/mL and FT4 levels were 0.86 ± 0.13 versus 1.24 ± 0.13 (ng/dL) in the case and control groups, respectively (P < 0.001). The serum level of 25(OH)D in the HT group was significantly lower than that in the control group (P < 0.001).
When serum 25(OH)D, TSH, and FT4 levels in different groups (case and control groups) were compared regarding the sex, we noticed a significant difference between male and female patients (P < 0.001) [Table 2].
|Table 1: Baseline characteristics and biochemical parameters of subjects|
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Biochemical parameters according to the presence of Vitamin D among different groups
Vitamin D deficiency was prevalent in 32.2% of the “HT group” (P < 0.001), whereas Vitamin D insufficiency was more prevalent in the “control group” in comparison with the “HT group” (23.1% vs. 13.2%; P < 0.001) [Figure 1].
|Figure 1: Different level of 25.hydroxyvitamin D among case and control groups|
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A comparison of the biochemical characteristics of the Vitamin D insufficiency and Vitamin D deficiency groups is shown in [Table 3]. The mean (±SD) serum 25(OH)D levels in patients with Vitamin D insufficiency (n = 107) and Vitamin D deficiency (n = 98) were 24.36 ± 2.95 and 14.16 ± 3.12 ng/mL, respectively (P < 0.001). The Vitamin D-deficient participants had a significantly higher TSH but lower FT4 level comparison to Vitamin D insufficient participants (TSH: 18.58 ± 8.73 vs. 8.52 ± 9.61 [μIU/mL]; FT4: 0.81 ± 0.15 vs. 1.12 ± 0.17 [ng/dL], respectively; P < 0.001) [Table 3].
|Table 3: Biochemical parameter based on different level of Vitamin D deficiency|
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Correlations between 25-hydroxyvitamin D and thyroid hormone levels
Regarding the control group, there were nonsignificant negative correlations between serum 25(OH)D and TSH (r = −0.121, P > 0.05) levels and nonsignificant positive correlations between serum 25(OH)D and FT4 (r = 0.045, P > 0.05) levels.
On the other hand, concerning the HT case group, there were significant negative correlations between serum 25(OH)D and TSH (r = −0.178, P < 0.05) and significant positive correlations between serum 25(OH)D and serum FT4 levels (r = 0.610, P < 0.001) [Figure 2] and [Figure 3].
|Figure 2: Correlation between 25-hydroxyvitamin D and thyroid-stimulating hormone (case group)|
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|Figure 3: Correlation between 25-hydroxyvitamin D and free thyroxine (case group)|
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| Discussion|| |
Vitamin D is known for its primary role in bone and mineral homeostasis, and it has been shown recently that Vitamin D has potent immunomodulatory effects and plays important roles in the pathogenesis of autoimmune diseases. Serum concentration of 25(OH)D is the best indicator of Vitamin D status. Few studies have been explained the role of Vitamin D in preventing AITD by modulating the immune cells. However, Vitamin D may affect thyroid function in other ways than modulating the immune system and preventing autoimmune diseases. A limited number of studies were performed in the field of evaluating Vitamin D effect in hypothyroid HT. Few studies have been conducted in order to find any significant association between the levels of Vitamin D and thyroid function.
In a study, Evliyaoğlu et al. showed that the prevalence of Vitamin D deficiency is more common in people with Hashimoto's than normal people. The results of the present study also indicate that Hashimoto's hypothyroidism patients deal with Vitamin D deficiency more than healthy people (P < 0.001). The results of the current study are in agreement with those of the other similar researches.,,
Several clinical studies have shown low Vitamin D status in patients with AITDs or HT, indicating an association between Vitamin D deficiency and thyroid autoimmunity., However, other studies showed no association between low Vitamin D status and thyroid autoimmunity.
Furthermore, the present study showed that lower serum Vitamin D levels were significantly associated with higher serum TSH and lower FT4 levels. We recorded a negative association between serum 25(OH)D and TSH levels and a positive association between serum 25(OH)D and FT4 levels in both the groups. However, the associations were significant among the HT case group; however, those were nonsignificant in the control group. Our results were in harmony with the previous studies that showed the prevalence of Vitamin D insufficiency in Hashimoto's cases was significantly higher than that observed in healthy controls. Finally, the results indicated that hypothyroid HT is associated with Vitamin D deficiency.
| Conclusions|| |
From the findings of our study, it can be concluded that patients with hypothyroid HT present with reduced serum 25(OH)D level. Moreover, the negative significant correlation between serum 25(OH)D with TSH levels and positive significant correlation with thyroxine (FT4) hormones suggested that deficiency of serum Vitamin D levels was significantly associated with hypothyroidism.
Limitations and recommendations
The present study has several limitations. There is the possibility of selection bias because participants were selected from patients who visited a tertiary hospital and were sampled. This study only investigated cross-sectional data of small number of participants. Therefore, the causal relationship was limited in its ability to conclude that Vitamin D status is directly related to the pathogenesis of hypothyroidism. Further studies with a larger number of participants are needed to determine whether Vitamin D deficiency is a causal factor in the pathogenesis of hypothyroid HT or rather a consequence of the disease.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Holick MF, Chen TC. Vitamin D deficiency: A worldwide problem with health consequences. Am J Clin Nutr 2008;87:1080S-6S.
Naeem Z. Vitamin D deficiency- an ignored epidemic. Int J Health Sci (Qassim) 2010;4:V-VI.
Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor? Arch Biochem Biophys 2012;523:123-33.
Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clinic Proc 2011;86:50-60.
Makariou S, Liberopoulos EN, Elisaf M, Challa A. Novel roles of vitamin D in disease: What is new in 2011? Eur J Intern Med 2011;22:355-62.
Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G, et al
. Prevalence of Vitamin D inadequacy among women with osteoporosis: An International epidemiological investigation. J Intern Med 2006:260:245-54.
Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Dankó K, et al
. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol 2011;8:243-47.
Haussler MR, Haussler CA, Jurutka PW, Thompson PD, Hsieh JC, Remus LS, et al
. The Vitamin D hormone and its nuclear receptor: Molecular actions and disease states. J Endocrinol. 1997;154:S57-73.
Tamer G, Arik S, Tamer I, Coksert D. Relative Vitamin D insufficiency in hashimoto's thyroiditis. Thyroid 2011;21:891-6.
Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, et al.
The nuclear Vitamin D receptor: Biological and molecular regulatory properties revealed. J Bone Miner Res 1998;13:325-49.
Mazokopakis EE, Kotsiris DA. Hashimoto's autoimmune thyroiditis and Vitamin D deficiency. Current aspects. Hell J Nucl Med 2014;17:37-40.
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;42:739-41.
Shin DY, Kim KJ, Kim D, Hwang S, Lee EJ. Low serum Vitamin D is associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei Med J 2014;55:476-81.
Altrichter S, Boodstein N, Maurer M. Matrix metalloproteinase-9: A novel biomarker for monitoring disease activity in patients with chronic urticaria patients? Allergy 2009;64:652-6.
Chambers ES, Hawrylowicz CM. The impact of vitamin D on regulatory T cells. Curr Allergy Asthma Rep 2011;11:29-36.
Evliyaoğlu O, Acar M, Özcabı B, Erginöz E, Bucak F, Ercan O, et al.
Vitamin D deficiency and hashimoto's thyroiditis in children and adolescents: A critical Vitamin D level for this association? J Clin Res Pediatr Endocrinol 2015;7:128-33.
Bozkurt NC, Karbek B, Ucan B, Sahin M, Cakal E, Ozbek M, et al.
The association between severity of Vitamin D deficiency and hashimoto's thyroiditis. Endocr Pract 2013;19:479-84.
Ucan B, Sahin M, Sayki Arslan M, Colak Bozkurt N, Kizilgul M, Güngünes A, et al.
Vitamin D treatment in patients with hashimoto's thyroiditis may decrease the development of hypothyroidism. Int J Vitam Nutr Res 2016;86:9-17.
Barchetta I, Baroni MG, Leonetti F, De Bernardinis M, Bertoccini L, Fontana M, et al
. TSH levels are associated with Vitamin D status and seasonality in an adult population of euthyroid adults. Clin Exp Med 2015;15:389-96.
Goswami R, Marwaha RK, Gupta N, Tandon N, Sreenivas V, Tomar N, et al.
Prevalence of Vitamin D deficiency and its relationship with thyroid autoimmunity in Asian Indians: A community-based survey. Br J Nutr 2009;102:382-6.
Holick MF. Vitamin D deficiency. N Engl JMed 2007;357:266-81.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]