Role of Supplementation with Selenium and Myo-inositol vs. Selenium alone in patients of Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis

Role of Supplementation with Selenium and Myo-inositol vs. Selenium alone in patients of Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis | 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 Role of Supplementation with Selenium and Myo-inositol vs. Selenium alone in patients of Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis Varisha Zuhair, Areeba Tufail Shaikh, Nimra Shafi, Areesha Babar, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4086168/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 Autoimmune thyroiditis (AIT) is a condition characterized by inflammation of the thyroid gland. Hashimoto’s thyroiditis is a predominant type, involving the gradual destruction of the thyroid gland. It affects females more than males, with global prevalence of around 10–12%. Multiple studies imply that a combination of selenium and myo-inositol supplements can restore a euthyroid state in patients with auto-immune thyroiditis. The objective of this meta-analysis is to pool available evidence on effectiveness of supplementation therapy on treatment of AIT. Methods: Google scholar and PubMed databases were searched for randomized controlled trials (RCTs) and observational studies which reported outcomes of combined treatment in restoring a euthyroid state, specifically comparing it with selenium-only treatment. Changes in TSH, T3, T4, TPOAb, and TgAb levels from baseline were defined as indicators to compare the effect of combined vs. selenium only treatment in restoring euthyroid levels. The Cochrane risk of bias tool and Newcastle Ottawa Scale were used to assess the quality of the randomized control trials included in the study. For statistical analysis, Review Manager (version 5.4, Nordic Cochrane Centre, Copenhagen, Denmark) was used. Result: We pooled 3 studies enrolling 151 participants in MI + Se group and 137 participants in Se group. Supplementation of Se with MI demonstrated a significant reduction in TSH levels compared to Se alone (SMD= -1.15, 95% CI: -1.60 to -0.69, p < 0.00001). MI + Se treatment also significantly reduced TgAb levels compared to Se (SMD= -0.51, 95% CI: -0.78 to -0.24, p = 0.0002). In contrast, TPOAB, T3 and T4 levels were non-significantly reduced from baseline in patients treated with MI + Se when compared to Se alone (SMD= -0.81, 95% CI: -0.44 to 0.09, p = 0.20), (SMD = 0.16, 95% CI: -0.09 to 0.42, p = 0.22), and (SMD = 0.30, 95% CI: -0.23 to 0.83, p = 0.26) respectively. Conclusion: Supplementation of Se with MI showed a significant reduction in TSH and TgAb levels compared to selenium-only treatment, with non-significant reduction in TPOAB, T3 and T4 levels. This entails the need for powered clinical trials and observational studies with longer follow-ups to critically assess the role of combined therapy in restoring euthyroid state in patients with AIT. Figures Figure 1 Figure 2 Introduction Autoimmune thyroiditis (AIT) implies a group of conditions in which there is inflammation of the thyroid gland secondary to thyroid autoantibodies, resulting in either hypothyroidism or hyperthyroidism. Among these conditions, Hashimoto's thyroiditis (HT), also referred to as chronic autoimmune thyroiditis and chronic lymphocytic thyroiditis is one of the most prevalent types. It is characterized by the gradual destruction of the thyroid gland via the body's own immune response. With a global prevalence of approximately 10–12% and a higher impact on females compared to males 1 , this disorder is widely recognized as the leading factor behind hypothyroidism. 2 Hashimoto’s thyroiditis is associated with many complications including thyroid carcinoma. 3 Therefore, prompt treatment is very crucial. Currently, thyroid hormone replacement therapy, specifically levothyroxine, also known as L-thyroxine, is considered the standard treatment for AIT. 4 This medication is a synthetic form of the thyroid hormone thyroxine, typically administered orally for lifelong treatment. In addition to this, a randomized, placebo-controlled prospective study indicated that simultaneous administration of selenium alongside L-thyroxine can serve as a potentially effective complementary treatment for AIT. 5 Selenium is an essential trace element that plays a critical role in supporting the activity of selenium-dependent enzymes with antioxidant and anti-inflammatory properties. It also helps to potentially enhance immune response and provide additional support for thyroid health. 6 Therefore, even mild selenium deficiency may contribute to the development of autoimmune thyroid diseases. Moreover, myo-inositol supplemented with selenium has been shown to be fruitful in curing HT. Myo-inositol acts via second messenger pathways and regulates H 2 O 2 -mediated iodination of thyroglobulin. 7 Various studies suggest that selenium in combination with myo-inositol can restore euthyroid state in Hashimoto's patients 8 . However, no prior meta-analysis has been conducted to evaluate the role of combination treatment in restoration of euthyroid levels, particularly for treatment for AIT. Therefore, we aim to assess the efficacy of Myo-Inositol in adjunction to Selenium for treatment of AIT, by pooling evidence from three distinct studies. Methodology This meta-analysis was carried out following the guidelines set by the Cochrane Collaboration and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) 9 and AMSTAR guidelines 10 . This study did not require an institutional board review because the data used was publicly available. This meta-analysis has been registered with Prospero ID: CRD42024500545 Search Strategy Two independent authors (Areeba and Nimra) conducted the literature search using PubMed and Google Scholar from inception till 2020 for randomized controlled trials and observational studies reporting the outcome with Myo inositol plus selenium supplements treatment in restoring euthyroid state compared with selenium only. We used a snowballing strategy and checked the reference lists of eligible articles to ensure no relevant articles were missed. The search strategy for each database is present in Supplementary Table 1 . Additionally, the reference lists of all included studies were manually examined to identify any supplementary studies. Two authors, (Areesha and Varisha), independently reviewed and extracted the data according to pre-established search criteria and conducted quality assessments. A third review author (Afnan) was involved to resolve any discrepancies. Eligibility criteria The following criteria were used to determine which studies would be included in this meta-analysis: Only randomised trials were taken into account. Once-weekly Insulin Icodec versus once-daily insulin glargine was being compared. Participants had to have Autoimmune thyroiditis. The studies had to evaluate any of the predetermined outcomes. The articles had to be written in English. Excluded from consideration were studies that: 1. lacked a control group 2. had overlapping study populations 3. involved non-human subjects 4. were not available in full texts Data Extraction and Study Quality Assessment : Two independent reviewers (Varisha and Areeba) thoroughly reviewed the publications, and trials that satisfied previously established criteria were only chosen. The decision to include/exclude an article was solely hierarchical with an initial inquiry of databases for title and abstract, followed by reviewing full texThe search strategy for each database is present in Supplementary Table 1. Additionally, the reference lists of all included studies were manually examined to identify any supplementary studies. Two authors, (Arooba and Hamza) independently reviewed and extracted the data according to pre-established search criteria and conducted quality assessments. A third review author (Areeb) was involved to resolve any discrepancies. Review of each article was done to determine relevance. Study characteristics and outcomes were abstracted from the finalized trials. Because this analysis includes randomized controlled trials the Cochrane risk of bias tool 11 was utilized to evaluate the studies' quality. Several aspects of bias were assessed, including selection bias, performance bias, attrition bias, and reporting bias. The New Ottawa Scale 12 (NOS) focuses on the choice of study subjects (four items), comparability between groups (two items) and outcome (three items, applicable to cohort studies). The NOS score of each study varied from 0 to 9 points (1 point for each item, 9 points in total). An original study with a NOS score ≥ 6 points was considered to be of “high quality.” NOS score less than 6 was considered to be "high risk". The quality assessment is summarised in Supplemetary tables 2a and 2b. Statistical Analysis All statistical analyses were performed using Review Manager (Version 5.4, Nordic Cochrane Centre, Copenhagen, Denmark). The evidence from trials was pooled using a random effect model and recorded as standard mean difference (SMD) with 95% confidence intervals (CIs). We pooled outcomes with ≥ 2 studies, and visualized them using forest plots. Higgins I2 was used to assess study heterogeneity, and I2 values less than 50% were considered acceptable 13 . A P value of less than 0.05 was considered significant in all cases. Results Literature Search results After a thorough search, 50 articles were identified, of which 17 were excluded after reading their title and abstract. A full-text review was conducted, after which 10 articles were excluded. A total of 3 articles met our inclusion and exclusion criteria. 8 , 14 , 15 Thus, the selection process is summarized in the PRISMA flow diagram (Fig. 1 ). Study characteristics and Quality assessment The included trials randomly assigned 288 patients of Autoimmune thyroiditis (AIT), with 151 people in the intervention group given Myoinositol plus Selenium and 137 in the control group given Selenium only. Overall, the studies continued for a period of 6 months, during which the patients were carefully followed up for T3, T4, TSH, TPOAb, and TgAb levels after receiving the combination therapy or monotherapy. The characteristics of the trials are highlighted in (Table 1 ). The Cochrane risk of bias tool was used to assess the risk of bias of each study. One study explicitly described the random sequence generated by the 1:1 randomization method 8 . And also described the way of allocation concealment by sealed boxes given to the participants 8 , thus its bias was considered to be "low risk" for selection bias. The other study only mentioned the word ‘randomization’ 14 . And did not mention if there was any allocation concealment 14 , thus its bias was considered to be ‘some concerns’ for selection bias. In both studies neither patients nor researchers knew the grouping, thus their bias was considered "low risk" for performance bias. No patients were lost to follow-up or dropped out in both studies, thus their bias was assessed as ‘low risk’ for ‘incomplete outcome data’. Both included studies showed a low bias risk in ‘selective reporting’ because their statistical outcomes were prespecified in the protocol. The quality of the observational study 15 was assessed through the newcastle-ottawa-scale tool. The study received 8 scores, thus its quality was considered to be "high quality". TSH levels Changes in TSH levels from baseline were assessed by 3 studies enrolling 151 participants in MI + Se group and 137 participants in Se alone group. The pooled analysis showed that participants who received combination treatment with MI + Se had significant reduction in TSH levels when compared to those who received monotherapy with Se (SMD= -1.15, 95% CI: -1.60 to -0.69, p < 0.00001) (Fig. 2 a). TgAb levels Changes in TgAb levels from baseline were assessed in two out of the three studies enrolling 108 participants in MI + Se group and 108 participants in Se group only. The pooled analysis showed that the participants who received a combination treatment with MI + Se had significantly reduced TgAb levels compared to monotherapy with Se (SMD= -0.51, 95% CI : -0.78 to -0.24, p = 0.0002) (Fig. 2 b) TPOAb Changes in TPOAb levels from baseline were assessed in two out of three studies enrolling 108 participants in MI + Se group and 108 participants in Se group only. The pooled analysis showed that the participants who received a combination treatment with MI + Se did not significantly reduce TPOAb levels compared to monotherapy with Se only (SMD= -0.81, 95% CI : -0.44 to 0.09, p = 0.20) ( Fig. 2 c) T3 levels (Fig. 2 d) Changes in TPOAb levels from baseline were assessed in two out of three studies enrolling 127 participants in MI + Se group and 113 participants in Se group only. The pooled analysis showed that the participants who recieved combination therapy with MI + Se had no significant effect on T3 levels compared to monotherapy Se only. (SMD = 0.16, 95% CI : -0.09 to 0.42, p = 0.22) (Fig. 2 d) T4 levels Changes in TPOAb levels from baseline were assessed in two out of three studies enrolling 127 participants in MI + Se group and 113 participants in Se group only. The pooled analysis showed that the participants who recieved combination therapy with MI + Se had no significant effect on T3 levels compared to monotherapy Se only.(SMD = 0.30, 95% CI : -0.23 to 0.83, p = 0.26) (Fig. 2 e) Discussion In this systematic review and meta-analysis, we found significantly reduced levels of TSH and TgAb in response to therapy with MI + Se as compared to exclusive Se therapy, in patients suffering from subclinical hypothyroidism due to AIT. Meanwhile, no significant changes were observed in the levels of TPOAb, fT3 and fT4 levels between both groups. To the best of our knowledge, our study is the first meta-analysis of its kind and it provides compelling evidence regarding the efficacy of MI + Se therapy in achieving a euthyroid state in patients suffering from AT, which is consistent with the findings reported by other RCTs. 8 , 14 In our meta-analysis, we found that TSH levels were significantly reduced in patients who were given oral MI + Se, versus those who received only Se. One possible explanation for these findings is that MI regulates TSH levels by the second messenger pathway, which not only controls its release, but also increases TSH sensitivity, which helps in the treatment of hypothyroidism 18 MI plays a crucial role in controlling thyroid function and its associated diseases. It is the most abundant stereoisomer of the inositol family, existing in 9 different forms, out of which MI is the most prevalent type in eukaryotic cells. Dietary items rich in Phytates (IP6) such as fresh fruits, vegetables, dried nuts, beans and cereals are some of the best sources of MI 19 . It is a precursor of Phosphatidylinositol 4, 5-bisphosphate (PIP2), which is itself a precursor of Inositol triphosphate (IP3), and IP3 is a second messenger of several hormones including TSH. Through its second messenger pathway, MI leads to the production of H 2 O 2 , which is required for the synthesis of thyroid hormones 17 . Therefore, depletion of MI, or abnormalities in the Inositol-dependent TSH signaling cascade can lead to the development of TSH resistance and hypothyroidism, and treatment with MI may raise the levels of the second messenger and improve TSH sensitivity, thus treating the hypothyroidism. 16 We also observed a significant reduction in TgAb levels of those who received MI + Se as compared to Se-only. This finding may be explained by the immune-modulatory role of MI and Se, by reducing the activity of regulatory T cells and preventing apoptosis. 18 Clinical studies have exhibited that after treatment with MI + Se, there was a decline in anti-thyroid autoantibodies as well as CXCL10 (an inflammatory chemokine), supporting the role of MI in immune modulation. 16 The role of Se in controlling thyroid activity can be estimated by the fact that out of all human organs, the thyroid gland contains the most Se g/tissue 19 in the form of Selenomethionine, Selenomethylselenocysteine, Methylselenol, Selenite, or is assimilated as Selenocysteine into Selenoproteins. 18 The levels of Se (which is a micronutrient) depend on population characteristics, diet, and soil composition. Se is necessary for the synthesis of deiodinases (DIOs) which result in deiodination of thyroxine (T4), converting it into its active form T3. 19 Sufficient intake of Se also helps in the breakdown of excess H 2 O 2 , by enhancing plasma glutathione peroxidase (GPX) and thioredoxin reductase (TR) levels, which give thyrocytes protection from peroxidases. 18 Selenium plays an important role in reducing inflammation by decreasing cytokine secretion. It also prevents follicular cell apoptosis by increasing CD4+/CD25 FOXP3 as well as the activity of regulatory T cells. 18 However, in our analysis of TPOAb, fT3 and fT4 levels, we found no significant changes in either group. Further studies that analyze various outcomes such as TPOAb, fT3, as well as fT4 levels are required to confirm our findings, considering that the outcomes that we analyzed were not sufficiently present in our included studies. Limitations: One limitation of this study is that we did not have access to individual patient data, and our meta-analysis was limited to the data that the authors of our included studies deemed relevant. Therefore, we were unable to precisely deny the involvement of other confounding factors in making the results significant, which may explain the high heterogeneity (I 2 = 72%) in one of our analyzed outcomes (fT4 levels). Secondly, only two out of our three included studies analyzed fT4 levels, and due to this limited data, we were unable to perform a sensitivity analysis. Future RCTs need to assess the efficacy of combining MI with Se and to also confirm if this therapy has any significant effect on fT3, fT4 as well as TPOAb. Currently, the available literature is insufficient to draw any decisive conclusions. Moreover, additional RCTs will enable researchers to systematically assess the outcomes to reinforce the results that we have reached in our study. Conclusion The combined therapy of Myo-inositol and selenium has a significant effect in treating Autoimmune Thyroiditis. The administration of Myo-inositol and selenium is highly effective in reducing TSH and TgAb levels. The potential of this combination is demonstrated in its ability to improve patient health and attain a euthyroid state in autoimmune thyroiditis patients. The positive outcome of this meta-analysis allows for the possibility of future clinical trials to investigate the efficacy of combined therapy in patients with autoimmune thyroiditis. Declarations Conflict of Interest: none Author Contribution VZ, ATS and NS conceptualized the project and performed a literature review. AB, AK and AS screened the articles as per inclusion criteria. VZ, AB and NS did data extraction from included studies and ATS, BK and KN did the data analysis. The results were combined by SHF and MAA and Quality assessment was done by MH. The tables and figures were prepared by MAA. 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Benvenga S, Nordio M, Laganà AS, Unfer V. The Role of Inositol in Thyroid Physiology and in Subclinical Hypothyroidism Management. Front Endocrinol (Lausanne). 2021;12:662582. doi: 10.3389/fendo.2021.662582 . PMID: 34040582; PMCID: PMC8143049. Duntas LH. The role of iodine and selenium in autoimmune thyroiditis. Hormone and Metabolic Research. 2015;47(10):721–6. Ventura M, Melo M, Carrilho F. Selenium and Thyroid Disease: From Pathophysiology to Treatment. Int J Endocrinol. 2017;2017:1297658. doi: 10.1155/2017/1297658 . Epub 2017 Jan 31. PMID: 28255299; PMCID: PMC5307254. Tables Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. 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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-4086168","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":279027613,"identity":"c4b7fe78-a71a-4a91-8091-cf8b750aebef","order_by":0,"name":"Varisha 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Sciences","correspondingAuthor":false,"prefix":"","firstName":"Syeda","middleName":"Haya","lastName":"Fatima","suffix":""},{"id":279027636,"identity":"844501c0-fcdc-498e-99b2-0b86ca78801b","order_by":11,"name":"Eman Ali","email":"","orcid":"","institution":"Dow University of Health Sciences","correspondingAuthor":false,"prefix":"","firstName":"Eman","middleName":"","lastName":"Ali","suffix":""}],"badges":[],"createdAt":"2024-03-12 16:23:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4086168/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4086168/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":52792405,"identity":"0ac27bb9-bf06-4732-9847-8acb53d31d09","added_by":"auto","created_at":"2024-03-15 20:18:04","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":389204,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePRISMA flow diagram\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4086168/v1/84a52fa49b852034338d6468.jpeg"},{"id":52792407,"identity":"6fcd4df0-28e1-400d-a095-4dc3eaf993f9","added_by":"auto","created_at":"2024-03-15 20:18:05","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":338504,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in TSH, TgAb, and TPOAb levels following MI + Se therapy vs. Se alone.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4086168/v1/cb98bf9def92574789b5e1e8.png"},{"id":53616767,"identity":"417a0745-6006-4ed6-bb92-5557b8a47ae3","added_by":"auto","created_at":"2024-03-28 06:50:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":704117,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4086168/v1/f64fd768-7b9b-461e-83d0-3a7689c7571e.pdf"},{"id":52792402,"identity":"1b47055f-9983-4520-b63a-0e8b53d2e36f","added_by":"auto","created_at":"2024-03-15 20:18:02","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":55967,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.png","url":"https://assets-eu.researchsquare.com/files/rs-4086168/v1/e029046e7e53bbdf5005a4c8.png"},{"id":52792410,"identity":"fb1296cb-7158-4ae8-b112-ed400c9d1e86","added_by":"auto","created_at":"2024-03-15 20:18:07","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":306854,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarytables.docx","url":"https://assets-eu.researchsquare.com/files/rs-4086168/v1/20cdf4b86122fed355fc6837.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Role of Supplementation with Selenium and Myo-inositol vs. Selenium alone in patients of Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAutoimmune thyroiditis (AIT) implies a group of conditions in which there is inflammation of the thyroid gland secondary to thyroid autoantibodies, resulting in either hypothyroidism or hyperthyroidism. Among these conditions, Hashimoto's thyroiditis (HT), also referred to as chronic autoimmune thyroiditis and chronic lymphocytic thyroiditis is one of the most prevalent types. It is characterized by the gradual destruction of the thyroid gland via the body's own immune response. With a global prevalence of approximately 10\u0026ndash;12% and a higher impact on females compared to males\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e, this disorder is widely recognized as the leading factor behind hypothyroidism.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Hashimoto\u0026rsquo;s thyroiditis is associated with many complications including thyroid carcinoma.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Therefore, prompt treatment is very crucial. Currently, thyroid hormone replacement therapy, specifically levothyroxine, also known as L-thyroxine, is considered the standard treatment for AIT. \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e This medication is a synthetic form of the thyroid hormone thyroxine, typically administered orally for lifelong treatment. In addition to this, a randomized, placebo-controlled prospective study indicated that simultaneous administration of selenium alongside L-thyroxine can serve as a potentially effective complementary treatment for AIT. \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSelenium is an essential trace element that plays a critical role in supporting the activity of selenium-dependent enzymes with antioxidant and anti-inflammatory properties. It also helps to potentially enhance immune response and provide additional support for thyroid health. \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Therefore, even mild selenium deficiency may contribute to the development of autoimmune thyroid diseases. Moreover, myo-inositol supplemented with selenium has been shown to be fruitful in curing HT. Myo-inositol acts via second messenger pathways and regulates H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e-mediated iodination of thyroglobulin.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Various studies suggest that selenium in combination with myo-inositol can restore euthyroid state in Hashimoto's patients \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. However, no prior meta-analysis has been conducted to evaluate the role of combination treatment in restoration of euthyroid levels, particularly for treatment for AIT. Therefore, we aim to assess the efficacy of Myo-Inositol in adjunction to Selenium for treatment of AIT, by pooling evidence from three distinct studies.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cp\u003eThis meta-analysis was carried out following the guidelines set by the Cochrane Collaboration and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis)\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e and AMSTAR guidelines\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. This study did not require an institutional board review because the data used was publicly available. This meta-analysis has been registered with Prospero ID: CRD42024500545\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eSearch Strategy\u003c/h2\u003e\n \u003cp\u003eTwo independent authors (Areeba and Nimra) conducted the literature search using PubMed and Google Scholar from inception till 2020 for randomized controlled trials and observational studies reporting the outcome with Myo inositol plus selenium supplements treatment in restoring euthyroid state compared with selenium only. We used a snowballing strategy and checked the reference lists of eligible articles to ensure no relevant articles were missed. The search strategy for each database is present in \u003cstrong\u003eSupplementary Table\u0026nbsp;1\u003c/strong\u003e. Additionally, the reference lists of all included studies were manually examined to identify any supplementary studies. Two authors, (Areesha and Varisha), independently reviewed and extracted the data according to pre-established search criteria and conducted quality assessments. A third review author (Afnan) was involved to resolve any discrepancies.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003eEligibility criteria\u003c/h2\u003e\n \u003cp\u003eThe following criteria were used to determine which studies would be included in this meta-analysis:\u003c/p\u003e\n \u003col\u003e\n \u003cli\u003eOnly randomised trials were taken into account.\u003c/li\u003e\n \u003cli\u003eOnce-weekly Insulin Icodec versus once-daily insulin glargine was being compared.\u003c/li\u003e\n \u003cli\u003eParticipants had to have Autoimmune thyroiditis.\u003c/li\u003e\n \u003cli\u003eThe studies had to evaluate any of the predetermined outcomes.\u003c/li\u003e\n \u003cli\u003eThe articles had to be written in English.\u003c/li\u003e\n \u003c/ol\u003e\n \u003cp\u003eExcluded from consideration were studies that:\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;1. lacked a control group\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;2. had overlapping study populations\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;3. \u0026nbsp; involved non-human subjects\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;4. were not available in full texts\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e\u003cstrong\u003eData Extraction and Study Quality Assessment\u003c/strong\u003e:\u003c/h2\u003e\n \u003cp\u003eTwo independent reviewers (Varisha and Areeba) thoroughly reviewed the publications, and trials that satisfied previously established criteria were only chosen. The decision to include/exclude an article was solely hierarchical with an initial inquiry of databases for title and abstract, followed by reviewing full texThe search strategy for each database is present in \u003cstrong\u003eSupplementary Table\u0026nbsp;1.\u003c/strong\u003e Additionally, the reference lists of all included studies were manually examined to identify any supplementary studies. Two authors, (Arooba and Hamza) independently reviewed and extracted the data according to pre-established search criteria and conducted quality assessments. A third review author (Areeb) was involved to resolve any discrepancies.\u003c/p\u003e\n \u003cp\u003eReview of each article was done to determine relevance. Study characteristics and outcomes were abstracted from the finalized trials. Because this analysis includes randomized controlled trials the Cochrane risk of bias tool \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e was utilized to evaluate the studies\u0026apos; quality. Several aspects of bias were assessed, including selection bias, performance bias, attrition bias, and reporting bias. The New Ottawa Scale \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e (NOS) focuses on the choice of study subjects (four items), comparability between groups (two items) and outcome (three items, applicable to cohort studies). The NOS score of each study varied from 0 to 9 points (1 point for each item, 9 points in total). An original study with a NOS score\u0026thinsp;\u0026ge;\u0026thinsp;6 points was considered to be of \u0026ldquo;high quality.\u0026rdquo; NOS score less than 6 was considered to be \u0026quot;high risk\u0026quot;. The quality assessment is summarised in \u003cstrong\u003eSupplemetary tables 2a and 2b.\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eAll statistical analyses were performed using Review Manager (Version 5.4, Nordic Cochrane Centre, Copenhagen, Denmark). The evidence from trials was pooled using a random effect model and recorded as standard mean difference (SMD) with 95% confidence intervals (CIs). We pooled outcomes with \u0026ge;\u0026thinsp;2 studies, and visualized them using forest plots. Higgins I2 was used to assess study heterogeneity, and I2 values less than 50% were considered acceptable\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. A P value of less than 0.05 was considered significant in all cases.\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eLiterature Search results\u003c/h2\u003e \u003cp\u003eAfter a thorough search, 50 articles were identified, of which 17 were excluded after reading their title and abstract. A full-text review was conducted, after which 10 articles were excluded. A total of 3 articles met our inclusion and exclusion criteria. \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Thus, the selection process is summarized in the PRISMA flow diagram (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStudy characteristics and Quality assessment\u003c/h2\u003e \u003cp\u003eThe included trials randomly assigned 288 patients of Autoimmune thyroiditis (AIT), with 151 people in the intervention group given Myoinositol plus Selenium and 137 in the control group given Selenium only. Overall, the studies continued for a period of 6 months, during which the patients were carefully followed up for T3, T4, TSH, TPOAb, and TgAb levels after receiving the combination therapy or monotherapy. The characteristics of the trials are highlighted in (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The Cochrane risk of bias tool was used to assess the risk of bias of each study. One study explicitly described the random sequence generated by the 1:1 randomization method \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. And also described the way of allocation concealment by sealed boxes given to the participants \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e, thus its bias was considered to be \"low risk\" for selection bias. The other study only mentioned the word \u0026lsquo;randomization\u0026rsquo; \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. And did not mention if there was any allocation concealment \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e, thus its bias was considered to be \u0026lsquo;some concerns\u0026rsquo; for selection bias. In both studies neither patients nor researchers knew the grouping, thus their bias was considered \"low risk\" for performance bias. No patients were lost to follow-up or dropped out in both studies, thus their bias was assessed as \u0026lsquo;low risk\u0026rsquo; for \u0026lsquo;incomplete outcome data\u0026rsquo;. Both included studies showed a low bias risk in \u0026lsquo;selective reporting\u0026rsquo; because their statistical outcomes were prespecified in the protocol. The quality of the observational study \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e was assessed through the newcastle-ottawa-scale tool. The study received 8 scores, thus its quality was considered to be \"high quality\".\u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eTSH levels\u003c/h2\u003e \u003cp\u003eChanges in TSH levels from baseline were assessed by 3 studies enrolling 151 participants in MI\u0026thinsp;+\u0026thinsp;Se group and 137 participants in Se alone group. The pooled analysis showed that participants who received combination treatment with MI\u0026thinsp;+\u0026thinsp;Se had significant reduction in TSH levels when compared to those who received monotherapy with Se (SMD= -1.15, 95% CI: -1.60 to -0.69, p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003eTgAb levels\u003c/h2\u003e \u003cp\u003eChanges in TgAb levels from baseline were assessed in two out of the three studies enrolling 108 participants in MI\u0026thinsp;+\u0026thinsp;Se group and 108 participants in Se group only. The pooled analysis showed that the participants who received a combination treatment with MI\u0026thinsp;+\u0026thinsp;Se had significantly reduced TgAb levels compared to monotherapy with Se (SMD= -0.51, 95% CI : -0.78 to -0.24, p\u0026thinsp;=\u0026thinsp;0.0002) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb)\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eTPOAb\u003c/h2\u003e \u003cp\u003eChanges in TPOAb levels from baseline were assessed in two out of three studies enrolling 108 participants in MI\u0026thinsp;+\u0026thinsp;Se group and 108 participants in Se group only. The pooled analysis showed that the participants who received a combination treatment with MI\u0026thinsp;+\u0026thinsp;Se did not significantly reduce TPOAb levels compared to monotherapy with Se only (SMD= -0.81, 95% CI : -0.44 to 0.09, p\u0026thinsp;=\u0026thinsp;0.20) \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e(\u003c/span\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec)\u003c/p\u003e \u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eT3 levels\u003c/span\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed)\u003c/p\u003e \u003cp\u003eChanges in TPOAb levels from baseline were assessed in two out of three studies enrolling 127 participants in MI\u0026thinsp;+\u0026thinsp;Se group and 113 participants in Se group only. The pooled analysis showed that the participants who recieved combination therapy with MI\u0026thinsp;+\u0026thinsp;Se had no significant effect on T3 levels compared to monotherapy Se only. (SMD\u0026thinsp;=\u0026thinsp;0.16, 95% CI : -0.09 to 0.42, p\u0026thinsp;=\u0026thinsp;0.22) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eT4 levels\u003c/h2\u003e \u003cp\u003eChanges in TPOAb levels from baseline were assessed in two out of three studies enrolling 127 participants in MI\u0026thinsp;+\u0026thinsp;Se group and 113 participants in Se group only. The pooled analysis showed that the participants who recieved combination therapy with MI\u0026thinsp;+\u0026thinsp;Se had no significant effect on T3 levels compared to monotherapy Se only.(SMD\u0026thinsp;=\u0026thinsp;0.30, 95% CI : -0.23 to 0.83, p\u0026thinsp;=\u0026thinsp;0.26) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ee)\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this systematic review and meta-analysis, we found significantly reduced levels of TSH and TgAb in response to therapy with MI\u0026thinsp;+\u0026thinsp;Se as compared to exclusive Se therapy, in patients suffering from subclinical hypothyroidism due to AIT. Meanwhile, no significant changes were observed in the levels of TPOAb, fT3 and fT4 levels between both groups. To the best of our knowledge, our study is the first meta-analysis of its kind and it provides compelling evidence regarding the efficacy of MI\u0026thinsp;+\u0026thinsp;Se therapy in achieving a euthyroid state in patients suffering from AT, which is consistent with the findings reported by other RCTs.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e In our meta-analysis, we found that TSH levels were significantly reduced in patients who were given oral MI\u0026thinsp;+\u0026thinsp;Se, versus those who received only Se. One possible explanation for these findings is that MI regulates TSH levels by the second messenger pathway, which not only controls its release, but also increases TSH sensitivity, which helps in the treatment of hypothyroidism \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e MI plays a crucial role in controlling thyroid function and its associated diseases. It is the most abundant stereoisomer of the inositol family, existing in 9 different forms, out of which MI is the most prevalent type in eukaryotic cells. Dietary items rich in Phytates (IP6) such as fresh fruits, vegetables, dried nuts, beans and cereals are some of the best sources of MI \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. It is a precursor of Phosphatidylinositol 4, 5-bisphosphate (PIP2), which is itself a precursor of Inositol triphosphate (IP3), and IP3 is a second messenger of several hormones including TSH. Through its second messenger pathway, MI leads to the production of H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e, which is required for the synthesis of thyroid hormones \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. Therefore, depletion of MI, or abnormalities in the Inositol-dependent TSH signaling cascade can lead to the development of TSH resistance and hypothyroidism, and treatment with MI may raise the levels of the second messenger and improve TSH sensitivity, thus treating the hypothyroidism.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWe also observed a significant reduction in TgAb levels of those who received MI\u0026thinsp;+\u0026thinsp;Se as compared to Se-only. This finding may be explained by the immune-modulatory role of MI and Se, by reducing the activity of regulatory T cells and preventing apoptosis.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Clinical studies have exhibited that after treatment with MI\u0026thinsp;+\u0026thinsp;Se, there was a decline in anti-thyroid autoantibodies as well as CXCL10 (an inflammatory chemokine), supporting the role of MI in immune modulation. \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe role of Se in controlling thyroid activity can be estimated by the fact that out of all human organs, the thyroid gland contains the most Se g/tissue\u003csup\u003e19\u003c/sup\u003e in the form of Selenomethionine, Selenomethylselenocysteine, Methylselenol, Selenite, or is assimilated as Selenocysteine into Selenoproteins. \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e The levels of Se (which is a micronutrient) depend on population characteristics, diet, and soil composition. Se is necessary for the synthesis of deiodinases (DIOs) which result in deiodination of thyroxine (T4), converting it into its active form T3.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Sufficient intake of Se also helps in the breakdown of excess H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e, by enhancing plasma glutathione peroxidase (GPX) and thioredoxin reductase (TR) levels, which give thyrocytes protection from peroxidases.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Selenium plays an important role in reducing inflammation by decreasing cytokine secretion. It also prevents follicular cell apoptosis by increasing CD4+/CD25 FOXP3 as well as the activity of regulatory T cells.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e However, in our analysis of TPOAb, fT3 and fT4 levels, we found no significant changes in either group. Further studies that analyze various outcomes such as TPOAb, fT3, as well as fT4 levels are required to confirm our findings, considering that the outcomes that we analyzed were not sufficiently present in our included studies.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitations:\u003c/h2\u003e \u003cp\u003eOne limitation of this study is that we did not have access to individual patient data, and our meta-analysis was limited to the data that the authors of our included studies deemed relevant. Therefore, we were unable to precisely deny the involvement of other confounding factors in making the results significant, which may explain the high heterogeneity (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;72%) in one of our analyzed outcomes (fT4 levels). Secondly, only two out of our three included studies analyzed fT4 levels, and due to this limited data, we were unable to perform a sensitivity analysis.\u003c/p\u003e \u003cp\u003eFuture RCTs need to assess the efficacy of combining MI with Se and to also confirm if this therapy has any significant effect on fT3, fT4 as well as TPOAb. Currently, the available literature is insufficient to draw any decisive conclusions. Moreover, additional RCTs will enable researchers to systematically assess the outcomes to reinforce the results that we have reached in our study.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe combined therapy of Myo-inositol and selenium has a significant effect in treating Autoimmune Thyroiditis. The administration of Myo-inositol and selenium is highly effective in reducing TSH and TgAb levels. The potential of this combination is demonstrated in its ability to improve patient health and attain a euthyroid state in autoimmune thyroiditis patients. The positive outcome of this meta-analysis allows for the possibility of future clinical trials to investigate the efficacy of combined therapy in patients with autoimmune thyroiditis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of Interest:\u003c/h2\u003e \u003cp\u003enone\u003c/p\u003e \u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eVZ, ATS and NS conceptualized the project and performed a literature review. AB, AK and AS screened the articles as per inclusion criteria. VZ, AB and NS did data extraction from included studies and ATS, BK and KN did the data analysis. The results were combined by SHF and MAA and Quality assessment was done by MH. The tables and figures were prepared by MAA. AK, AS and VZ wrote the discussion. The manuscript was compiled and reviewed by EA.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWiersinga, W.M. (2018). Hashimoto\u0026rsquo;s Thyroiditis. 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Int J Endocrinol. 2017;2017:1297658. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2017/1297658\u003c/span\u003e\u003cspan address=\"10.1155/2017/1297658\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2017 Jan 31. PMID: 28255299; PMCID: PMC5307254.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\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":"","lastPublishedDoi":"10.21203/rs.3.rs-4086168/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4086168/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAutoimmune thyroiditis (AIT) is a condition characterized by inflammation of the thyroid gland. Hashimoto\u0026rsquo;s thyroiditis is a predominant type, involving the gradual destruction of the thyroid gland. It affects females more than males, with global prevalence of around 10\u0026ndash;12%. Multiple studies imply that a combination of selenium and myo-inositol supplements can restore a euthyroid state in patients with auto-immune thyroiditis. The objective of this meta-analysis is to pool available evidence on effectiveness of supplementation therapy on treatment of AIT.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eGoogle scholar and PubMed databases were searched for randomized controlled trials (RCTs) and observational studies which reported outcomes of combined treatment in restoring a euthyroid state, specifically comparing it with selenium-only treatment. Changes in TSH, T3, T4, TPOAb, and TgAb levels from baseline were defined as indicators to compare the effect of combined vs. selenium only treatment in restoring euthyroid levels. The Cochrane risk of bias tool and Newcastle Ottawa Scale were used to assess the quality of the randomized control trials included in the study. For statistical analysis, Review Manager (version 5.4, Nordic Cochrane Centre, Copenhagen, Denmark) was used.\u003c/p\u003e\u003ch2\u003eResult:\u003c/h2\u003e \u003cp\u003eWe pooled 3 studies enrolling 151 participants in MI\u0026thinsp;+\u0026thinsp;Se group and 137 participants in Se group. Supplementation of Se with MI demonstrated a significant reduction in TSH levels compared to Se alone (SMD= -1.15, 95% CI: -1.60 to -0.69, p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001). MI\u0026thinsp;+\u0026thinsp;Se treatment also significantly reduced TgAb levels compared to Se (SMD= -0.51, 95% CI: -0.78 to -0.24, p\u0026thinsp;=\u0026thinsp;0.0002). In contrast, TPOAB, T3 and T4 levels were non-significantly reduced from baseline in patients treated with MI\u0026thinsp;+\u0026thinsp;Se when compared to Se alone (SMD= -0.81, 95% CI: -0.44 to 0.09, p\u0026thinsp;=\u0026thinsp;0.20), (SMD\u0026thinsp;=\u0026thinsp;0.16, 95% CI: -0.09 to 0.42, p\u0026thinsp;=\u0026thinsp;0.22), and (SMD\u0026thinsp;=\u0026thinsp;0.30, 95% CI: -0.23 to 0.83, p\u0026thinsp;=\u0026thinsp;0.26) respectively.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eSupplementation of Se with MI showed a significant reduction in TSH and TgAb levels compared to selenium-only treatment, with non-significant reduction in TPOAB, T3 and T4 levels. This entails the need for powered clinical trials and observational studies with longer follow-ups to critically assess the role of combined therapy in restoring euthyroid state in patients with AIT.\u003c/p\u003e","manuscriptTitle":"Role of Supplementation with Selenium and Myo-inositol vs. Selenium alone in patients of Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-15 20:17:33","doi":"10.21203/rs.3.rs-4086168/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":"7a8ade0f-3a70-4549-af59-051f7dea64ab","owner":[],"postedDate":"March 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-28T06:42:40+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-15 20:17:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4086168","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4086168","identity":"rs-4086168","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}