Vitamin D deficiency and TSH level, a relationship in nonautoimmune hypothyroidism pediatrics

Vitamin D deficiency and TSH level, a relationship in nonautoimmune hypothyroidism pediatrics | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Vitamin D deficiency and TSH level, a relationship in nonautoimmune hypothyroidism pediatrics Mohadeseh MohammadTaheri, Seyed Alinaghi Kazemi, Farzane Ahmadi, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3939344/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and purpose : Vitamin D has a crucial role in the organs' function and is essential for specific populations like pediatrics. Indeed, the thyroid function correlates with the Vitamin D level in the body, so the consequences of this depletion are very important. In non-autoimmune hypothyroidism, the Vitamin D level influences the thyroid function which could be tracked with thyroid stimulating hormone. Design and methods: In this cross-sectional study, among 2,503 children aged three to 18 who were referred to the pediatrics endocrinology and metabolic clinic in Zanjan city in 2022-2023, 102 children with non-autoimmune hypothyroidism who did not have a history of other diseases or the use of drugs affecting thyroid function in last three months were selected and entered this study. Data were analyzed by IBM SPSS 24 using binary logistic regression. Results: The mean (standard deviation) vitamin D level in the study population was 27.66 (13.17) ng/ml, with a deficiency prevalence of 63.7%. The odds of vitamin D deficiency significantly increased 70 percent with one unit (mIU)/liter (L) increasing in TSH (OR=1.70, CI 95%:1.19-2.43, P= 0.003. However, weight, height, sex, age, body mass index, and season had no statistically significant relationship. Conclusions: The level of vitamin D and TSH level have a positive correlation in non-autoimmune hypothyroidism pediatric patients. Indeed, the correcting vitamin D deficiently reduces the TSH level. So, we can use vitamin D supplements along with other treatments in treating hypothyroidism. Vitamin D Thyroid stimulating hormone TSH Non-autoimmune hypothyroidism children Figures Figure 1 Figure 2 1. Introduction Hypothyroidism, with a prevalence ranging from 0.3–3.7% in the general population of the United States, and from 0.2–5.3% in Europe, may manifest with symptoms such as unexplained weight gain, fatigue, cold intolerance, delayed growth, or puberty in pediatrics. The diagnosis of primary hypothyroidism relies on a high Thyroid stimulating hormone (TSH) level in the blood, indicating the sensitivity of the hypothalamic-pituitary axis to thyroid hormone changes, including thyroxine (T4) and the more bioactive hormone tri-iodothyronine (T3). The initial stage of hypothyroidism is characterized by elevated TSH levels and normal thyroid hormone levels. Hypothyroidism frequently arises due to autoimmune activity, specifically chronic autoimmune thyroiditis or Hashimoto thyroiditis. However, it can also manifest as a consequence of modified iodine levels, hereditary genetic modifications, neoplasms, or neoplastic therapies such as surgery, radiotherapy, or immune checkpoint inhibitors ( 1 – 4 ). Hypothyroidism in children leads to impaired growth, behavioral issues, and symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). These conditions can potentially be reversed if treated promptly and accurately. The most significant consequences of untreated or under-treated hypothyroidism in children are associated with a deficiency in neuropsychological development, cognitive abilities, and obtaining an appropriate education. Therefore they frequently fail to become independent adults. This condition also has significant socioeconomic impacts on both the individual and society ( 5 ). In addition, hypothyroidism development is affected by multiple factors such as genetic variants, medications, infections, environmental factors, tumors or diseases or some of their treatment, and nutrition ( 1 ). One of the important nutrients is vitamin D which performs various functions via receptors expressed in many body organs, such as regulating ion homeostasis, cellular growth, differentiation, and immunity ( 6 ). This particular vitamin exerts its biological effects via nuclear vitamin D receptors in most human cells and tissues, including the endocrine system ( 7 ) which plays a crucial role in controlling and managing the expression of over 1,000 genes ( 8 ). Several mechanisms exist by which vitamin D may modify the concentrations of TSH and thyroid hormones ( 9 ). Experimental research indicates that vitamin D directly affects type 2 iodothyronine deiodinase (Dio2), an enzyme required for converting T4 into T3 in target tissues. Specifically, diabetic rats administered vitamin D experience increased Dio2 expression levels in the liver and brain, resulting in elevated free tri-iodothyronine (fT3) levels and reduced free thyroxine (fT4) levels ( 10 ). In-vitro investigations have demonstrated that vitamin D infusion can potentially suppress TSH-stimulated adenylyl cyclase activity and iodide uptake. Conversely, in a rat pituitary cell study, it has been observed that vitamin D administration leads to an increase in Thyrotropin-releasing hormone (TRH) -induced TSH release. These findings suggest that vitamin D may have central and peripheral impacts on releasing TSH and thyroid hormones ( 9 ). Many studies have been conducted on the effect of vitamin D on TSH levels ( 9 ). Most of these studies have been conducted in adults or those with autoimmune hypothyroidism. However new studies show that causes unrelated to the immune system can also cause this relationship. As far as we know, no study has been done to investigate the effect of vitamin D in pediatrics with non-autoimmune hypothyroidism. Considering hypothyroidism's critical role in pediatrics’ growth and development, the present study was conducted to investigate the effect of vitamin D on the level of TSH and the prevalence of vitamin D deficiency in pediatrics with non-autoimmune hypothyroidism. Also, the relationship between the plurality of vitamin D deficiency and age, sex, height, weight, body mass index (BMI), and season in the subjects of this study was investigated. 2. Material and Methods 2.1 Study Population and Ethical Considerations In the present cross-sectional study, the medical documents of 2,503 children aged three to 18 referred to the Pediatrics Endocrine and Metabolic Clinic in Zanjan from January 2022 to May 2023 were analyzed. After obtaining written informed consent from parents or legal guardian, 129 children and adolescents aged three to 18 diagnosed with hypothyroidism were included in our study. In the last three months, these children and adolescents should not have received drug treatment such as thyroxine, anti-thyroid drugs, and drugs affecting thyroid function such as glucocorticoids, anti-leptics, and oral contraceptive pills (OCPs). These children were either diagnosed for the first time or did not need thyroid medication due to their recovery in the last three months. Also, children should not have liver, kidney, heart diseases, cancers, diabetes, and diseases affecting vitamin D synthesis, such as limited movement, immobility, and recent hospitalizations. Patients were excluded from the study in case of incomplete medical documents, lack of access to patients during the study, non-cooperation of parents in completing incomplete data, and positive anti-thyroid peroxidase (anti-TPO). The study flow diagram is shown in Fig. 2 . Also, the study got approval from the Ethics Committee (No. IR.ZUMS.REC.1401.153) from Zanjan University of Medical Sciences. All patient information remained confidential, and there was no additional cost for the patients. Written informed consent was obtained from all parents or legal guardian of patients in this study. 2.2 Data Collection and Outcome Definition Demographic characteristics such as age and gender were obtained from children's medical documents and records. In this study, we used children's height in centimeters and their weight in kilograms recorded on the day they visited the clinic. Also, these data were used to calculate the BMI with the weight formula (in kilograms) on the square of height (in meters). All the tests were done in the Mousavi Hospital laboratory in Zanjan city. The vitamin D and TSH levels were measured by Chemiluminescent micro-particle immune assay (CMIA) (Abbott, Architect Reagent kit USA). The required information was extracted from the medical documents of the final 102 children and adolescents included in the study. The study data collection form containing research variables including sex, age, weight, height, BMI, vitamin D level, TSH level, and the date of the tests were recorded for the statistical population under study. Demographic information and TSH and vitamin D levels of participants are presented in Table 1 . Table 1 Description of Season, height, weight, and BMI. Variable Category Frequency Percent Season Spring 31 30.4 Summer 31 30.4 Autumn 15 14.7 Winter 25 24.5 Z score for height Z < -2 8 7.8 -2 < Z 2 7 6.9 Z score for weight Z < -2 2 2.0 -2 < Z 2 16 15.7 Z score for BMI Z < -2 1 1.0 -2 < Z 2 22 21.6 According to the Endocrine Society's Practice Guidelines Committee, the National Osteoporosis Foundation, the International Osteoporosis Foundation, the American Association for Clinical Endocrinologists, and the American Geriatric Society, Vitamin D above 30 nanograms (ng)/milliliter (mL) is considered sufficient. In vitamin D less than 30 ng/ml, In the published Endocrine Society's Practice Guidelines on Vitamin D, vitamin D deficiency was defined as a 25(OH)D < 20 ng/mL, insufficiency as 21–29 ng/mL. The American Association of Clinical Endocrinologists represents vitamin D deficiency below 30 ng/ml ( 11 – 13 ). This study defined vitamin D deficiency below 30 ng/ml and vitamin D above 30 ng/ml as sufficient. The level of TSH was collected based on milliunits per liter from the first sheet of tests requested, and a value higher than five was considered hypothyroid (subclinical or primary hypothyroid). In this study, we used children's height in centimeters and their weight in kilograms recorded on the day they visited the clinic. Also, these data were used to calculate the BMI with the weight formula (in kilograms) on the square of height (in meters). The sex of the children was recorded based on the physical phenotype of a girl or a boy. Children's age was considered based on the month from birth to the time of visiting the clinic. The date on which the requested tests were performed was collected from the test sheet and, based on that, divided into four seasons: spring, summer, autumn, and winter. This information was collected from the children's medical documents and records. 2.3 Statistical analysis Data were analyzed with IBM SPSS version 24 software. The quantitative variables were described as mean (standard deviation, SD), and qualitative variables were expressed as numbers (percent). Because our statistical population is children and appropriate height, weight, and BMI in children are defined based on other children of the same age and sex, we standardized the variables of size, weight, and BMI based on the Standard Deviation Score (SDS) formula and the 2000 CDC (Centers for Disease Control and Prevention) growth chart. The Z scores were calculated for height, weight, and BMI and categorized as less than − 2 (abnormal), between 2 and − 2 (normal), and greater than 2 (abnormal). Normality was checked by Shapiro-Wilk or Kolmogorov-Smirnov tests. The independent t-test was used to study the relationship between qualitative and quantitative on the level of vitamin D as deficiency or sufficient) the univariate and multiple binary logistic regression was used. Also, the significance level was assumed to be equal to 0.05. 3. Results Of the 102 individuals studied, the mean (SD) of age was 8.38 (2.90) years in rage 3.42–16.42 years, and 58 (56.9%) were girls. Most of the participants were referred in spring and summer (60.8%) and had normal height (85.3%), weight (82.4%), and BMI (77.5%), based on Z scores (Table 1 ). The mean (SD) of TSH was 6.93 (2.53) in the range of 5.00-21.30. Indeed, the mean (SD) of vitamin D level was 27.65 (13.17) ng/ml. Of 102, 3 (2.9%) children and adolescents had vitamin D below 10 ng/ml, 26 (25.5%) children and adolescents had vitamin D 10–20 ng/ml, 36 (35.3%) children and adolescents had vitamin D 20–30 ng/ml, and 37 (36.3%) children and adolescents had vitamin D above 30 ng/ml. As a result, 36.3% had normal vitamin D levels (> 30 ng/ml), and 63.7% had vitamin D deficiency (< 30 ng/ml). The boxplot of TSH based on vitamin D deficiency and non-deficiency is shown in Fig. 1 . The level of TSH is lower in children and adolescents who have vitamin D deficiency. The binary logistic regression showed a significant relationship between the TSH and vitamin D, that the odds of vitamin D deficiency increased 70 percent with one unit (mIU)/liter (L) increasing in TSH (OR = 1.70, CI 95%:1.19–2.43, P = 0.003). Table 2 includes the binary logistic regression results to investigate the relationship between age, gender, season, height, weight, and BMI on vitamin D deficiency. They had no relationship with vitamin D deficiency. Table 2 Univariate binary logistic regression to investigate effect variables on vitamin D status. Variables Category Vitamin D level P-value OR (CI 95%) Sufficient Insufficient Age - 8.05 (2.70) 8.57 (3.02) 0.385 1.07 (0.92, 1.23) Gender Girl 21 (36.2) 37 (63.8) 0.987 1.02 (0.45, 2.27) Boy (Reverence) 16 (36.4) 28 (63.6) Season Spring 11 (35.5) 20 (64.5) 0.345 1.68 (0.57, 4.92) Summer 9 (29.0) 22 (71.0) 0.148 2.26 (0.75, 6.80) Autumn 5 (33.3) 10 (66.7) 0.366 1.85 (0.49, 6.98) Winter (Reference) 12 (48.0) 13 (52.0) - - Weight Normal 32 (38.1) 52 (61.9) 0.411 0.62 (0.20, 1.92) Abnormal (Reference) 5 (27.8) 13 (72.2) - - Height Normal 31 (35.6) 56 (64.4) 0.745 1.20 (0.39, 3.70) Abnormal (Reference) 6 (40.0) 9 (60.0) - - BMI Normal 30 (38.0) 49 (62.0) 0.509 0.71 (0.26, 1.94) Abnormal (Reference) 7 (30.4) 16 (69.6) - - The multiple binary logistic regression was fitted to consider simultaneously the relationship between all variables age, gender, season, height, weight, and BMI along with TSH on vitamin D deficiency. The adjusted OR (CI 95%) of TSH was equal to 1.78 (1.23–2.57). 4. Discussion The present study was conducted to investigate the relationship between vitamin D and TSH levels in children with non-autoimmune hypothyroidism. Three findings emerged from the present study. First, the prevalence of vitamin D deficiency in children with non-autoimmune hypothyroidism was 63.7% (65/102). Second, there was a significant negative relationship between levels of vitamin D and TSH in children with non-autoimmune hypothyroidism. Third, the prevalence of vitamin D did not correlate with age and sex in children with non-autoimmune hypothyroidism. Our study showed that the mean level of vitamin D in the population was 27.65 ng/ml, of which 36.3% (37/202) had sufficient vitamin D levels (above 30 ng/ml), and 63.7% (65/102) had insufficient vitamin D level (below 30 ng/ml). Studies in recent years in cities near Zanjan and with a similar angle of sunlight have shown the prevalence of vitamin D deficiency in the children's population to be 54.9% and 51% ( 14 , 15 ). In addition, In the meta-analysis study by Jazayeri et al. on Iranian children under 18, 61% had vitamin D less than 30 ng/ml ( 16 ). As a result, the prevalence of vitamin D deficiency is higher in hypothyroid children in our study. These findings agree with previous studies results ( 17 , 18 ). In addition, the level of vitamin D is affected by the angle of sunlight and the amount of air pollution, which can cause different prevalence in studies conducted in different cities. The present study suggests an inverse relationship between vitamin D levels and TSH in children with non-autoimmune hypothyroidism. This aligns with evidence demonstrating vitamin D supplementation's impact on TSH in autoimmune thyroid disease ( 18 , 19 ). Galusca et al.'s meta-analysis exemplifies this, demonstrating decreased TSH and thyroid antibodies upon supplementation ( 19 ). Similarly, Metwalley et al.'s study in children with autoimmune hypothyroidism yielded comparable results ( 18 ). These findings suggest a potential, albeit complex, interaction between vitamin D and thyroid function, extending beyond our specific population. Beyond its immunomodulatory role in autoimmune hypothyroidism, vitamin D may also influence TSH levels through diverse mechanisms. However, research specifically focused on our target population remains limited. Ahi et al.'s case-control study linked non-autoimmune hypothyroidism in adults to vitamin D deficiency, suggesting a potential underlying connection ( 20 ). Notably, Pezeshki et al.'s randomized clinical trial demonstrated that vitamin D supplementation significantly lowered TSH levels in adult patients with subclinical hypothyroidism and vitamin D deficiency ( 21 ). This aligns with our study's findings and supports the potential benefit of supplementation in this population. Furthermore, Zhou et al.'s study identified a statistically significant negative correlation between vitamin D and TSH, similar to our observations. Interestingly, they attributed this association to impaired thyroid hormone sensitivity ( 22 ). In contrast, Jiang et al.'s and Waterhouse's did not identify significant associations between vitamin D and TSH, highlighting the need for further exploration ( 23 , 24 ). Factors such as baseline vitamin D levels, study design variations, and intervention specifics likely contribute to these discrepancies. Additionally, Gou et al.'s and Evliyaoğlu et al.’s study in younger children with confounding factors underscore the importance of diverse population representation and robust methodologies in future research endeavors ( 25 , 26 ). Recent discoveries suggest that vitamin D could potentially exert an immunomodulatory impact on autoimmune hypothyroid through various mechanisms such as influencing DC-dependent T-cell activation, decreasing the expression of human leukocyte antigens (HLA) class II genes in the thyroid, preventing an exaggerated B-cell response, and maintaining a balanced Th17/Treg cell ratio ( 27 ). Another study with the same results showed that an optimal nutritional status of vitamin D appears to promote a noteworthy enhancement in an individual's levels of thyroid hormone and inflammatory profile ( 28 ). In addition to the anti-inflammatory role of vitamin D, it causes improvement in antioxidant status and oxidative stress reduction. More studies are needed in this field ( 29 ). Our study revealed no significant correlation between vitamin D prevalence and either age or sex in our pediatric population. While this aligns with several previous studies ( 20 , 30 ), some discordant findings necessitate further discussion. For instance, Babaniamansour et al. reported a negative association between age and vitamin D levels ( 14 ). Similarly, Jazayeri et al. observed a higher prevalence of deficiency in Iranian girls compared to boys ( 16 ). These heteregenous findings potentially stem from cultural factors specific to the Iranian population, such as differences in clothing practices (e.g., hijab use) and sun exposure habits between genders and age groups ( 31 ). Furthermore, limited access to public spaces for physical activity and inadequate indoor/outdoor activity participation among women and girls could contribute to these disparities. 5. Limitations Our statistical population was limited due to the limitation of the number of children with hypothyroidism in Zanjan city. The boundaries of the research were the incompleteness of the medical documents (6 medical documents) and the non-cooperation of the parents (7 items) in completing the data. Additionally, we could not gather data on the physical activity, use of supplements, sunscreen use, and socioeconomic status of the children in our study. 6. Conclusion and Recommendations Vitamin D plays an essential role in thyroid function, and in children with non-autoimmune hypothyroidism, vitamin D deficiency is higher in people with higher TSH levels. As a result, this study has a significant inverse relationship between vitamin D and TSH levels (p < 0.001(. The correction of vitamin D deficiency may reduce the level of TSH. As a result, this reduction reduces the long-term use of levothyroxine, multiple tests, and hypothyroid complications in children, so it is suggested considering the critical role of thyroid hormones in the growth and development of children, the relatively high frequency of vitamin D deficiency in hypothyroid patients and the possibility of the effect of vitamin D in lowering the level of TSH, Vitamin D should be given to children with hypothyroidism to lower TSH levels. Investigating the relationship of vitamin D with other laboratory parameters of thyroid, BMI, weight, height, and season in a larger population is recommended. It is also recommended to conduct clinical trials and studies on vitamin D correction in non-autoimmune hypothyroidism in children. Abbreviations TSH: Thyroid stimulating hormone, BMI: Body mass index, ng: nanogram, ml: milliliter, L: liter, mIU: micro international unit, CDC: Centers for Disease Control and Prevention, SDS: Standard Deviation Score, Dio2: type 2 iodothyronine deiodinase, T3: triiodothyronine, T4: thyroxine, fT3: free triiodothyronine, fT4: free thyroxine, TRH: Thyrotropin-releasing hormone, OCP : Oral contraceptive pills, anti-TPO: anti-thyroid peroxidase, CMIA: chemiluminescent microparticle immune assay, HLA: human leukocyte antigens, ADHD: Attention-Deficit/Hyperactivity Disorder, SD: standard deviation. Declarations Acknowledgment We want to thank the pediatrics Endocrine and Metabolic Clinic of Zanjan and the research assistant of Zanjan University of Medical Sciences for providing facilities for this study. We also thank Dr. Poudineh for their valuable guidance and support in this study. Conflict of Interest Disclosures: The authors declare no conflict of interest. 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Syst Rev Controlled Trials Antioxid. 2023;12(10):1798. Chailurkit L-o, Aekplakorn W, Ongphiphadhanakul B. High vitamin D status in younger individuals is associated with low circulating thyrotropin. Thyroid. 2013;23(1):25–30. Kazemi A, Sharifi F, Jafari N, Mousavinasab N. High prevalence of vitamin D deficiency among pregnant women and their newborns in an Iranian population. J women's health. 2009;18(6):835–9. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3939344","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":273345762,"identity":"1902c1e6-3962-4b45-af20-015dd182b315","order_by":0,"name":"Mohadeseh MohammadTaheri","email":"","orcid":"","institution":"Zanjan University in Medical Science","correspondingAuthor":false,"prefix":"","firstName":"Mohadeseh","middleName":"","lastName":"MohammadTaheri","suffix":""},{"id":273345763,"identity":"1f9990a8-ad1c-45ff-8c4c-cb80c634ecea","order_by":1,"name":"Seyed Alinaghi Kazemi","email":"","orcid":"","institution":"Mousavi Hospital, Zanjan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Seyed","middleName":"Alinaghi","lastName":"Kazemi","suffix":""},{"id":273345764,"identity":"42e3899a-d7c0-4cee-9f1b-8f841447b189","order_by":2,"name":"Farzane Ahmadi","email":"","orcid":"","institution":"Zanjan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Farzane","middleName":"","lastName":"Ahmadi","suffix":""},{"id":273345765,"identity":"6dc7d0c2-35ff-4083-b690-3159dc894b18","order_by":3,"name":"Kaveh Hadiloo","email":"","orcid":"","institution":"Zanjan University in Medical Science","correspondingAuthor":false,"prefix":"","firstName":"Kaveh","middleName":"","lastName":"Hadiloo","suffix":""},{"id":273345766,"identity":"bc804ad0-0408-470f-80d6-f1f71e03a377","order_by":4,"name":"Ziba Molaei","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYPACGx5+EJVQQLyWNDnJBpAWA+K1HDY2OACiidEiP+34M6kbf5gTN59fnfjhgQGDPL/YAfxaGGcnpEnntrElbrvxdrME0GGGM2cn4NfCLJ1wTDq3gQeo5ewGkJYEg9sEtLBJJ7ZJ5/yRSNw84+zmH0Rp4ZFOZpPOYTMwNuDv3UacLRLSaczWuW0JchI3eLdZJBhIEPaL/Oz0h7dz/vzn4e8/u/nmjwobeX5pAlqQ7AOrlCBWOQjwHyBF9SgYBaNgFIwkAAA+70EMf5NgwQAAAABJRU5ErkJggg==","orcid":"","institution":"Mousavi Hospital, Zanjan University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Ziba","middleName":"","lastName":"Molaei","suffix":""}],"badges":[],"createdAt":"2024-02-08 08:45:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3939344/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3939344/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51333282,"identity":"31e4c7a2-43e5-4dfc-be6b-7d9aae52b352","added_by":"auto","created_at":"2024-02-19 18:03:40","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":28309,"visible":true,"origin":"","legend":"\u003cp\u003eTSH level by vitamin D.\u003c/p\u003e","description":"","filename":"fig.1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3939344/v1/da57395c3180ccb0f975e7da.jpg"},{"id":51333284,"identity":"0ce8a522-92a5-4413-a49b-741a3a766d20","added_by":"auto","created_at":"2024-02-19 18:03:40","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":58754,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flow diagram.\u003c/p\u003e","description":"","filename":"fig.2..jpg","url":"https://assets-eu.researchsquare.com/files/rs-3939344/v1/39e5a856112572b178a90621.jpg"},{"id":59993777,"identity":"4b226fe7-9245-459b-aac0-398a85dd461c","added_by":"auto","created_at":"2024-07-10 09:05:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":600314,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3939344/v1/f0a6f2a9-da6f-4ecd-a77e-e078c45a24a0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Vitamin D deficiency and TSH level, a relationship in nonautoimmune hypothyroidism pediatrics","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eHypothyroidism, with a prevalence ranging from 0.3\u0026ndash;3.7% in the general population of the United States, and from 0.2\u0026ndash;5.3% in Europe, may manifest with symptoms such as unexplained weight gain, fatigue, cold intolerance, delayed growth, or puberty in pediatrics. The diagnosis of primary hypothyroidism relies on a high Thyroid stimulating hormone (TSH) level in the blood, indicating the sensitivity of the hypothalamic-pituitary axis to thyroid hormone changes, including thyroxine (T4) and the more bioactive hormone tri-iodothyronine (T3). The initial stage of hypothyroidism is characterized by elevated TSH levels and normal thyroid hormone levels. Hypothyroidism frequently arises due to autoimmune activity, specifically chronic autoimmune thyroiditis or Hashimoto thyroiditis. However, it can also manifest as a consequence of modified iodine levels, hereditary genetic modifications, neoplasms, or neoplastic therapies such as surgery, radiotherapy, or immune checkpoint inhibitors (\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Hypothyroidism in children leads to impaired growth, behavioral issues, and symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). These conditions can potentially be reversed if treated promptly and accurately. The most significant consequences of untreated or under-treated hypothyroidism in children are associated with a deficiency in neuropsychological development, cognitive abilities, and obtaining an appropriate education. Therefore they frequently fail to become independent adults. This condition also has significant socioeconomic impacts on both the individual and society (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In addition, hypothyroidism development is affected by multiple factors such as genetic variants, medications, infections, environmental factors, tumors or diseases or some of their treatment, and nutrition (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). One of the important nutrients is vitamin D which performs various functions via receptors expressed in many body organs, such as regulating ion homeostasis, cellular growth, differentiation, and immunity (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). This particular vitamin exerts its biological effects via nuclear vitamin D receptors in most human cells and tissues, including the endocrine system (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) which plays a crucial role in controlling and managing the expression of over 1,000 genes (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Several mechanisms exist by which vitamin D may modify the concentrations of TSH and thyroid hormones (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Experimental research indicates that vitamin D directly affects type 2 iodothyronine deiodinase (Dio2), an enzyme required for converting T4 into T3 in target tissues. Specifically, diabetic rats administered vitamin D experience increased Dio2 expression levels in the liver and brain, resulting in elevated free tri-iodothyronine (fT3) levels and reduced free thyroxine (fT4) levels (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). \u003cem\u003eIn-vitro\u003c/em\u003e investigations have demonstrated that vitamin D infusion can potentially suppress TSH-stimulated adenylyl cyclase activity and iodide uptake. Conversely, in a rat pituitary cell study, it has been observed that vitamin D administration leads to an increase in Thyrotropin-releasing hormone (TRH) -induced TSH release. These findings suggest that vitamin D may have central and peripheral impacts on releasing TSH and thyroid hormones (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMany studies have been conducted on the effect of vitamin D on TSH levels (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Most of these studies have been conducted in adults or those with autoimmune hypothyroidism. However new studies show that causes unrelated to the immune system can also cause this relationship. As far as we know, no study has been done to investigate the effect of vitamin D in pediatrics with non-autoimmune hypothyroidism.\u003c/p\u003e \u003cp\u003eConsidering hypothyroidism's critical role in pediatrics\u0026rsquo; growth and development, the present study was conducted to investigate the effect of vitamin D on the level of TSH and the prevalence of vitamin D deficiency in pediatrics with non-autoimmune hypothyroidism. Also, the relationship between the plurality of vitamin D deficiency and age, sex, height, weight, body mass index (BMI), and season in the subjects of this study was investigated.\u003c/p\u003e"},{"header":"2. Material and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Population and Ethical Considerations\u003c/h2\u003e \u003cp\u003eIn the present cross-sectional study, the medical documents of 2,503 children aged three to 18 referred to the Pediatrics Endocrine and Metabolic Clinic in Zanjan from January 2022 to May 2023 were analyzed. After obtaining written informed consent from parents or legal guardian, 129 children and adolescents aged three to 18 diagnosed with hypothyroidism were included in our study. In the last three months, these children and adolescents should not have received drug treatment such as thyroxine, anti-thyroid drugs, and drugs affecting thyroid function such as glucocorticoids, anti-leptics, and oral contraceptive pills (OCPs). These children were either diagnosed for the first time or did not need thyroid medication due to their recovery in the last three months. Also, children should not have liver, kidney, heart diseases, cancers, diabetes, and diseases affecting vitamin D synthesis, such as limited movement, immobility, and recent hospitalizations. Patients were excluded from the study in case of incomplete medical documents, lack of access to patients during the study, non-cooperation of parents in completing incomplete data, and positive anti-thyroid peroxidase (anti-TPO). The study flow diagram is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAlso, the study got approval from the Ethics Committee (No. IR.ZUMS.REC.1401.153) from Zanjan University of Medical Sciences. All patient information remained confidential, and there was no additional cost for the patients. Written informed consent was obtained from all parents or legal guardian of patients in this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Data Collection and Outcome Definition\u003c/h2\u003e \u003cp\u003eDemographic characteristics such as age and gender were obtained from children's medical documents and records. In this study, we used children's height in centimeters and their weight in kilograms recorded on the day they visited the clinic. Also, these data were used to calculate the BMI with the weight formula (in kilograms) on the square of height (in meters).\u003c/p\u003e \u003cp\u003eAll the tests were done in the Mousavi Hospital laboratory in Zanjan city. The vitamin D and TSH levels were measured by Chemiluminescent micro-particle immune assay (CMIA) (Abbott, Architect Reagent kit USA). The required information was extracted from the medical documents of the final 102 children and adolescents included in the study. The study data collection form containing research variables including sex, age, weight, height, BMI, vitamin D level, TSH level, and the date of the tests were recorded for the statistical population under study. Demographic information and TSH and vitamin D levels of participants are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDescription of Season, height, weight, and BMI.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercent\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eSeason\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eSpring\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eSummer\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAutumn\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eWinter\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eZ score for height\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eZ \u0026lt; -2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e-2\u0026thinsp;\u0026lt;\u0026thinsp;Z\u0026thinsp;\u0026lt;\u0026thinsp;2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e85.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eZ\u0026thinsp;\u0026gt;\u0026thinsp;2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eZ score for weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eZ \u0026lt; -2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e-2\u0026thinsp;\u0026lt;\u0026thinsp;Z\u0026thinsp;\u0026lt;\u0026thinsp;2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e82.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eZ\u0026thinsp;\u0026gt;\u0026thinsp;2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eZ score for BMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eZ \u0026lt; -2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e-2\u0026thinsp;\u0026lt;\u0026thinsp;Z\u0026thinsp;\u0026lt;\u0026thinsp;2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e77.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eZ\u0026thinsp;\u0026gt;\u0026thinsp;2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e According to the Endocrine Society's Practice Guidelines Committee, the National Osteoporosis Foundation, the International Osteoporosis Foundation, the American Association for Clinical Endocrinologists, and the American Geriatric Society, Vitamin D above 30 nanograms (ng)/milliliter (mL) is considered sufficient. In vitamin D less than 30 ng/ml, In the published Endocrine Society's Practice Guidelines on Vitamin D, vitamin D deficiency was defined as a 25(OH)D\u0026thinsp;\u0026lt;\u0026thinsp;20 ng/mL, insufficiency as 21\u0026ndash;29 ng/mL. The American Association of Clinical Endocrinologists represents vitamin D deficiency below 30 ng/ml (\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This study defined vitamin D deficiency below 30 ng/ml and vitamin D above 30 ng/ml as sufficient. The level of TSH was collected based on milliunits per liter from the first sheet of tests requested, and a value higher than five was considered hypothyroid (subclinical or primary hypothyroid).\u003c/p\u003e \u003cp\u003eIn this study, we used children's height in centimeters and their weight in kilograms recorded on the day they visited the clinic. Also, these data were used to calculate the BMI with the weight formula (in kilograms) on the square of height (in meters). The sex of the children was recorded based on the physical phenotype of a girl or a boy. Children's age was considered based on the month from birth to the time of visiting the clinic. The date on which the requested tests were performed was collected from the test sheet and, based on that, divided into four seasons: spring, summer, autumn, and winter. This information was collected from the children's medical documents and records.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Statistical analysis\u003c/h2\u003e \u003cp\u003eData were analyzed with IBM SPSS version 24 software. The quantitative variables were described as mean (standard deviation, SD), and qualitative variables were expressed as numbers (percent). Because our statistical population is children and appropriate height, weight, and BMI in children are defined based on other children of the same age and sex, we standardized the variables of size, weight, and BMI based on the Standard Deviation Score (SDS) formula and the 2000 CDC (Centers for Disease Control and Prevention) growth chart. The Z scores were calculated for height, weight, and BMI and categorized as less than \u0026minus;\u0026thinsp;2 (abnormal), between 2 and \u0026minus;\u0026thinsp;2 (normal), and greater than 2 (abnormal).\u003c/p\u003e \u003cp\u003eNormality was checked by Shapiro-Wilk or Kolmogorov-Smirnov tests. The independent t-test was used to study the relationship between qualitative and quantitative on the level of vitamin D as deficiency or sufficient) the univariate and multiple binary logistic regression was used. Also, the significance level was assumed to be equal to 0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eOf the 102 individuals studied, the mean (SD) of age was 8.38 (2.90) years in rage 3.42\u0026ndash;16.42 years, and 58 (56.9%) were girls. Most of the participants were referred in spring and summer (60.8%) and had normal height (85.3%), weight (82.4%), and BMI (77.5%), based on Z scores (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The mean (SD) of TSH was 6.93 (2.53) in the range of 5.00-21.30. Indeed, the mean (SD) of vitamin D level was 27.65 (13.17) ng/ml. Of 102, 3 (2.9%) children and adolescents had vitamin D below 10 ng/ml, 26 (25.5%) children and adolescents had vitamin D 10\u0026ndash;20 ng/ml, 36 (35.3%) children and adolescents had vitamin D 20\u0026ndash;30 ng/ml, and 37 (36.3%) children and adolescents had vitamin D above 30 ng/ml. As a result, 36.3% had normal vitamin D levels (\u0026gt;\u0026thinsp;30 ng/ml), and 63.7% had vitamin D deficiency (\u0026lt;\u0026thinsp;30 ng/ml).\u003c/p\u003e \u003cp\u003eThe boxplot of TSH based on vitamin D deficiency and non-deficiency is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The level of TSH is lower in children and adolescents who have vitamin D deficiency. The binary logistic regression showed a significant relationship between the TSH and vitamin D, that the odds of vitamin D deficiency increased 70 percent with one unit (mIU)/liter (L) increasing in TSH (OR\u0026thinsp;=\u0026thinsp;1.70, CI 95%:1.19\u0026ndash;2.43, P\u0026thinsp;=\u0026thinsp;0.003). Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e includes the binary logistic regression results to investigate the relationship between age, gender, season, height, weight, and BMI on vitamin D deficiency. They had no relationship with vitamin D deficiency.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate binary logistic regression to investigate effect variables on vitamin D status.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eVitamin D level\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOR (CI 95%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eSufficient\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eInsufficient\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8.05 (2.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.57 (3.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.385\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.07 (0.92, 1.23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eGirl\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21 (36.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e37 (63.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.987\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.02 (0.45, 2.27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eBoy (Reverence)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eSeason\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eSpring\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (35.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20 (64.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.68 (0.57, 4.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eSummer\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (29.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22 (71.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.148\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.26 (0.75, 6.80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAutumn\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.366\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.85 (0.49, 6.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eWinter (Reference)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (48.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13 (52.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eWeight\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNormal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32 (38.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52 (61.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.411\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.62 (0.20, 1.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAbnormal (Reference)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (27.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13 (72.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eHeight\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNormal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31 (35.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e56 (64.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.745\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.20 (0.39, 3.70)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAbnormal (Reference)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNormal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30 (38.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e49 (62.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.509\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.71 (0.26, 1.94)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAbnormal (Reference)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (30.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16 (69.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe multiple binary logistic regression was fitted to consider simultaneously the relationship between all variables age, gender, season, height, weight, and BMI along with TSH on vitamin D deficiency. The adjusted OR (CI 95%) of TSH was equal to 1.78 (1.23\u0026ndash;2.57).\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe present study was conducted to investigate the relationship between vitamin D and TSH levels in children with non-autoimmune hypothyroidism. Three findings emerged from the present study. First, the prevalence of vitamin D deficiency in children with non-autoimmune hypothyroidism was 63.7% (65/102). Second, there was a significant negative relationship between levels of vitamin D and TSH in children with non-autoimmune hypothyroidism. Third, the prevalence of vitamin D did not correlate with age and sex in children with non-autoimmune hypothyroidism.\u003c/p\u003e \u003cp\u003eOur study showed that the mean level of vitamin D in the population was 27.65 ng/ml, of which 36.3% (37/202) had sufficient vitamin D levels (above 30 ng/ml), and 63.7% (65/102) had insufficient vitamin D level (below 30 ng/ml). Studies in recent years in cities near Zanjan and with a similar angle of sunlight have shown the prevalence of vitamin D deficiency in the children's population to be 54.9% and 51% (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In addition, In the meta-analysis study by Jazayeri et al. on Iranian children under 18, 61% had vitamin D less than 30 ng/ml (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). As a result, the prevalence of vitamin D deficiency is higher in hypothyroid children in our study. These findings agree with previous studies results (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). In addition, the level of vitamin D is affected by the angle of sunlight and the amount of air pollution, which can cause different prevalence in studies conducted in different cities.\u003c/p\u003e \u003cp\u003eThe present study suggests an inverse relationship between vitamin D levels and TSH in children with non-autoimmune hypothyroidism. This aligns with evidence demonstrating vitamin D supplementation's impact on TSH in autoimmune thyroid disease (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Galusca et al.'s meta-analysis exemplifies this, demonstrating decreased TSH and thyroid antibodies upon supplementation (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Similarly, Metwalley et al.'s study in children with autoimmune hypothyroidism yielded comparable results (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). These findings suggest a potential, albeit complex, interaction between vitamin D and thyroid function, extending beyond our specific population. Beyond its immunomodulatory role in autoimmune hypothyroidism, vitamin D may also influence TSH levels through diverse mechanisms. However, research specifically focused on our target population remains limited. Ahi et al.'s case-control study linked non-autoimmune hypothyroidism in adults to vitamin D deficiency, suggesting a potential underlying connection (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Notably, Pezeshki et al.'s randomized clinical trial demonstrated that vitamin D supplementation significantly lowered TSH levels in adult patients with subclinical hypothyroidism and vitamin D deficiency (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). This aligns with our study's findings and supports the potential benefit of supplementation in this population. Furthermore, Zhou et al.'s study identified a statistically significant negative correlation between vitamin D and TSH, similar to our observations. Interestingly, they attributed this association to impaired thyroid hormone sensitivity (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). In contrast, Jiang et al.'s and Waterhouse's did not identify significant associations between vitamin D and TSH, highlighting the need for further exploration (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Factors such as baseline vitamin D levels, study design variations, and intervention specifics likely contribute to these discrepancies. Additionally, Gou et al.'s and Evliyaoğlu et al.\u0026rsquo;s study in younger children with confounding factors underscore the importance of diverse population representation and robust methodologies in future research endeavors (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Recent discoveries suggest that vitamin D could potentially exert an immunomodulatory impact on autoimmune hypothyroid through various mechanisms such as influencing DC-dependent T-cell activation, decreasing the expression of human leukocyte antigens (HLA) class II genes in the thyroid, preventing an exaggerated B-cell response, and maintaining a balanced Th17/Treg cell ratio (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Another study with the same results showed that an optimal nutritional status of vitamin D appears to promote a noteworthy enhancement in an individual's levels of thyroid hormone and inflammatory profile (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). In addition to the anti-inflammatory role of vitamin D, it causes improvement in antioxidant status and oxidative stress reduction. More studies are needed in this field (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur study revealed no significant correlation between vitamin D prevalence and either age or sex in our pediatric population. While this aligns with several previous studies (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e), some discordant findings necessitate further discussion. For instance, Babaniamansour et al. reported a negative association between age and vitamin D levels (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Similarly, Jazayeri et al. observed a higher prevalence of deficiency in Iranian girls compared to boys (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). These heteregenous findings potentially stem from cultural factors specific to the Iranian population, such as differences in clothing practices (e.g., hijab use) and sun exposure habits between genders and age groups (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Furthermore, limited access to public spaces for physical activity and inadequate indoor/outdoor activity participation among women and girls could contribute to these disparities.\u003c/p\u003e"},{"header":"5. Limitations","content":"\u003cp\u003eOur statistical population was limited due to the limitation of the number of children with hypothyroidism in Zanjan city. The boundaries of the research were the incompleteness of the medical documents (6 medical documents) and the non-cooperation of the parents (7 items) in completing the data. Additionally, we could not gather data on the physical activity, use of supplements, sunscreen use, and socioeconomic status of the children in our study.\u003c/p\u003e"},{"header":"6. Conclusion and Recommendations","content":"\u003cp\u003eVitamin D plays an essential role in thyroid function, and in children with non-autoimmune hypothyroidism, vitamin D deficiency is higher in people with higher TSH levels. As a result, this study has a significant inverse relationship between vitamin D and TSH levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001(. The correction of vitamin D deficiency may reduce the level of TSH. As a result, this reduction reduces the long-term use of levothyroxine, multiple tests, and hypothyroid complications in children, so it is suggested considering the critical role of thyroid hormones in the growth and development of children, the relatively high frequency of vitamin D deficiency in hypothyroid patients and the possibility of the effect of vitamin D in lowering the level of TSH, Vitamin D should be given to children with hypothyroidism to lower TSH levels. Investigating the relationship of vitamin D with other laboratory parameters of thyroid, BMI, weight, height, and season in a larger population is recommended. It is also recommended to conduct clinical trials and studies on vitamin D correction in non-autoimmune hypothyroidism in children.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eTSH:\u0026nbsp;\u003c/strong\u003eThyroid stimulating hormone, \u003cstrong\u003eBMI:\u0026nbsp;\u003c/strong\u003eBody mass index,\u003cstrong\u003e\u0026nbsp;ng:\u003c/strong\u003e nanogram,\u003cstrong\u003e\u0026nbsp;ml:\u003c/strong\u003e milliliter,\u003cstrong\u003e\u0026nbsp;L:\u003c/strong\u003e liter,\u003cstrong\u003e\u0026nbsp;mIU:\u0026nbsp;\u003c/strong\u003emicro international unit,\u003cstrong\u003e\u0026nbsp;CDC:\u003c/strong\u003e Centers for Disease Control and Prevention,\u003cstrong\u003e\u0026nbsp;SDS:\u003c/strong\u003e Standard Deviation Score, \u003cstrong\u003eDio2:\u003c/strong\u003e type 2 iodothyronine deiodinase, \u003cstrong\u003eT3:\u003c/strong\u003e triiodothyronine, \u003cstrong\u003eT4:\u003c/strong\u003e thyroxine, \u003cstrong\u003efT3:\u003c/strong\u003e free\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003etriiodothyronine, \u003cstrong\u003efT4:\u003c/strong\u003e free thyroxine, \u003cstrong\u003eTRH:\u0026nbsp;\u003c/strong\u003eThyrotropin-releasing hormone, \u003cstrong\u003eOCP\u003c/strong\u003e: Oral contraceptive pills, \u003cstrong\u003eanti-TPO:\u003c/strong\u003e anti-thyroid peroxidase, \u003cstrong\u003eCMIA:\u003c/strong\u003e chemiluminescent microparticle immune assay, \u003cstrong\u003eHLA:\u003c/strong\u003e human leukocyte antigens, \u003cstrong\u003eADHD:\u003c/strong\u003e Attention-Deficit/Hyperactivity Disorder, \u003cstrong\u003eSD:\u0026nbsp;\u003c/strong\u003estandard deviation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe want to thank the pediatrics Endocrine and Metabolic Clinic of Zanjan and the research assistant of Zanjan University of Medical Sciences for providing facilities for this study.\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eWe also thank Dr. Poudineh for their\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003evaluable guidance and support in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosures:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere isn\u0026rsquo;t any additional data, but the data sets are available in the Pediatric Endocrine and Metabolic Clinic of Zanjan University of Medical Sciences. They would be shared with anyone providing the reason for using the dataset by contacting the corresponding author.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding/Support:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChaker L, Razvi S, Bensenor IM, Azizi F, Pearce EN, Peeters RP, Hypothyroidism (Primer), editors. Nature Reviews: Disease Primers. 2022;8(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Vries L, Bulvik S, Phillip M. Chronic autoimmune thyroiditis in children and adolescents: at presentation and during long-term follow-up. Arch Dis Child. 2009;94(1):33\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeged\u0026uuml;s L, Bianco AC, Jonklaas J, Pearce SH, Weetman AP, Perros P. Primary hypothyroidism and quality of life. 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BMC Endocr Disorders. 2021;21(1):1\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarlberg C. Vitamin D: a micronutrient regulating genes. Curr Pharm Design. 2019;25(15):1740\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBabić Leko M, Jureško I, Rozić I, Pleić N, Gunjača I, Zemunik T. Vitamin D and the Thyroid: A Critical Review of the Current Evidence. Int J Mol Sci. 2023;24(4):3586.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlrefaie Z, Awad H. Effect of vitamin D3 on thyroid function and de-iodinase 2 expression in diabetic rats. Arch Physiol Biochem. 2015;121(5):206\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCamacho PM, Petak SM, Binkley N, Clarke BL, Harris ST, Hurley DL, et al. American Association Of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis\u0026mdash;2016\u0026ndash;executive summary. Endocr Pract. 2016;22(9):1111\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolick MF. The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Reviews Endocr Metabolic Disorders. 2017;18:153\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolick 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 metabolism. 2011;96(7):1911\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBabaniamansour S, Hematyar M, Babaniamansour P, Babaniamansour A, Aliniagerdroudbari E. The prevalence of vitamin D deficiency among one to six year old children of Tehran, Iran. J Kermanshah Univ Med Sci. 2019;23(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRezaiee GA, Mojarrad M, Taghinezhad H, Zamaan J, Akbari TA, Sadegh H et al. Frequency of Vitamin D Deficiency in the Children below Fifteen Admitted To the 523 Hospital, Urmia. 2019.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJazayeri M, Moradi Y, Rasti A, Nakhjavani M, Kamali M, Baradaran HR. Prevalence of vitamin D deficiency in healthy Iranian children: A systematic review and meta-analysis. Med J Islamic Repub Iran. 2018;32:83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAppunni S, Rubens M, Ramamoorthy V, Saxena A, Tonse R, Veledar E, et al. Association between vitamin D deficiency and hypothyroidism: results from the National Health and Nutrition Examination Survey (NHANES) 2007\u0026ndash;2012. BMC Endocr disorders. 2021;21(1):1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMetwalley K, Farghaly H, Sherief T, Hussein A. Vitamin D status in children and adolescents with autoimmune thyroiditis. J Endocrinol Investig. 2016;39:793\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalușca D, Popoviciu MS, Babeș EE, Vidican M, Zaha AA, Babeș VV, et al. Vitamin D implications and effect of supplementation in endocrine disorders: autoimmune thyroid disorders (Hashimoto\u0026rsquo;s disease and Grave\u0026rsquo;s disease), diabetes mellitus and obesity. Medicina. 2022;58(2):194.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhi S, Dehdar MR, Hatami N. Vitamin D deficiency in non-autoimmune hypothyroidism: a case-control study. BMC Endocr disorders. 2020;20(1):1\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePezeshki B, Ahmadi A, Karimi A. The Effect of Vitamin D Replacement on Patient with Subclinical Hypothyroidism: A Pilot Randomized Clinical Trial. Galen Med J. 2020;9:e1592.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou L, Wang Y, Su J, An Y, Liu J, Wang G. Vitamin D Deficiency is Associated with impaired sensitivity to thyroid hormones in Euthyroid adults. Nutrients. 2023;15(17):3697.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiang H, Chen X, Qian X, Shao S. Effects of vitamin D treatment on thyroid function and autoimmunity markers in patients with Hashimoto's thyroiditis\u0026mdash;A meta-analysis of randomized controlled trials. J Clin Pharm Ther. 2022;47(6):767\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWaterhouse M, Pham H, Rahman ST, Baxter C, Duarte Romero B, Armstrong BK et al. The effect of vitamin D supplementation on hypothyroidism in the randomized controlled D-Health Trial. Thyroid. 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEvliyaoğlu O, Acar M, \u0026Ouml;zcabı B, Ergin\u0026ouml;z E, Bucak F, Ercan O, et al. Vitamin D deficiency and Hashimoto\u0026rsquo;s thyroiditis in children and adolescents: A critical vitamin D level for this association? J Clin Res Pediatr Endocrinol. 2015;7(2):128.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuo Y, Wu C-Y, Deng Y-H, Wu J-L. Associations between serum 25-hydroxyvitamin D levels and thyroid function parameters in previously healthy children aged 6 to 24 months. Risk Manage Healthc Policy. 2020:1647\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLebiedziński F, Lisowska KA. Impact of Vitamin D on Immunopathology of Hashimoto\u0026rsquo;s Thyroiditis: From Theory to Practice. Nutrients. 2023;15(14):3174.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFran\u0026ccedil;a R, Cordeiro A, Pereira SE, Saboya CJ, Ramalho A. The Effect of Vitamin D Adequacy on Thyroid Hormones and Inflammatory Markers after Bariatric Surgery. Metabolites. 2023;13(5):603.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKubiak K, Szmidt MK, Kaluza J, Zylka A, Sicinska E. Do Dietary Supplements Affect Inflammation, Oxidative Stress, and Antioxidant Status in Adults with Hypothyroidism or Hashimoto\u0026rsquo;s Disease?\u0026mdash;A. Syst Rev Controlled Trials Antioxid. 2023;12(10):1798.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChailurkit L-o, Aekplakorn W, Ongphiphadhanakul B. High vitamin D status in younger individuals is associated with low circulating thyrotropin. Thyroid. 2013;23(1):25\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKazemi A, Sharifi F, Jafari N, Mousavinasab N. High prevalence of vitamin D deficiency among pregnant women and their newborns in an Iranian population. J women's health. 2009;18(6):835\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Vitamin D, Thyroid stimulating hormone, TSH, Non-autoimmune hypothyroidism, children","lastPublishedDoi":"10.21203/rs.3.rs-3939344/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3939344/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and purpose\u003c/strong\u003e: Vitamin D has a crucial role in the organs' function and is essential for specific populations like pediatrics. Indeed, the thyroid function correlates with the Vitamin D level in the body, so the consequences of this depletion are very important. In non-autoimmune hypothyroidism, the Vitamin D level influences the thyroid function which could be tracked with thyroid stimulating hormone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDesign and methods:\u003c/strong\u003e In this cross-sectional study, among 2,503 children aged three to 18 who were referred to the pediatrics endocrinology and metabolic clinic in Zanjan city in 2022-2023, 102 children with non-autoimmune hypothyroidism who did not have a history of other diseases or the use of drugs affecting thyroid function in last three months were selected and entered this study. Data were analyzed by IBM SPSS 24 using binary logistic regression.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The mean (standard deviation) vitamin D level in the study population was 27.66 (13.17) ng/ml, with a deficiency prevalence of 63.7%. The odds of vitamin D deficiency significantly increased 70 percent with one unit (mIU)/liter (L) increasing in TSH (OR=1.70, CI 95%:1.19-2.43, P= 0.003. However, weight, height, sex, age, body mass index, and season had no statistically significant relationship.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e The level of vitamin D and TSH level have a positive correlation in non-autoimmune hypothyroidism pediatric patients. Indeed, the correcting vitamin D deficiently reduces the TSH level. So, we can use vitamin D supplements along with other treatments in treating hypothyroidism.\u003c/p\u003e","manuscriptTitle":"Vitamin D deficiency and TSH level, a relationship in nonautoimmune hypothyroidism pediatrics","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-19 18:03:34","doi":"10.21203/rs.3.rs-3939344/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ca4a36d7-7871-4d11-b2f8-9beffb6154cc","owner":[],"postedDate":"February 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-10T08:57:36+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-19 18:03:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3939344","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3939344","identity":"rs-3939344","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}