Unlocking the Therapeutic Potential: Selenium and Myo-Inositol Supplementation in Thyroid Disorders—Efficacy and Future Directions

<b>Background/Objectives</b>: Thyroid disorders such as Hashimoto's thyroiditis and Graves' disease represent major endocrine challenges worldwide, often requiring long-term management. Recently, nutritional supplementation with selenium and myo-inositol has been proposed as a supportive strategy. This review aims to summarize the current evidence regarding their efficacy in improving thyroid function, reducing thyroid autoantibodies in Hashimoto's disease, and restoring biochemical euthyroidism in Graves' disease. <b>Methods</b>: A narrative review of the available literature was undertaken, concentrating on randomized controlled trials and observational studies evaluating selenium and myo-inositol, alone or in combination (MYO+Se), in patients with autoimmune thyroid disorders and benign thyroid nodules. <b>Search Strategy and Study Selection</b>: We searched MEDLINE/PubMed, Embase, Cochrane CENTRAL, and Scopus from inception to 31 July 2025. The search used Boolean operators to combine the following keywords: ("selenium" OR "selenomethionine") AND ("myo-inositol" OR "inositol") AND (thyroid OR Hashimoto* OR Graves' OR hyperthyroid* OR hypothyroid* OR nodule* OR goiter OR orbitopathy). We included human studies in English. <b>Inclusion criteria</b>: Research designs include RCTs, quasi-experimental studies, cohort/case-control studies, and big case series (<i>n</i> ≥ 30). <b>Exclusion criteria</b>: Animal-only or in vitro studies (unless mechanistic), pediatric case reports, and editorials/commentaries. <b>Study selection and data extraction:</b> Two reviewers screened independently; discrepancies were settled through consensus. The data retrieved included the population, baseline iodine/selenium status (if reported), dose/formulation, treatment duration, outcomes (TSH, FT4, FT3, TPOAb, TgAb, TRAb, nodule metrics), and adverse events. <b>Quality assessment</b>: The risk of bias was assessed using the RoB-2 for RCTs and the Newcastle-Ottawa Scale or JBI checklists for observational studies. A qualitative synthesis emphasized study quality, consistency, directness, and accuracy. <b>Results</b>: Clinical research indicate that selenium supplementation may reduce thyroid peroxidase antibody (TPOAb) levels in Hashimoto's disease, thereby attenuating autoimmune activity. Myo-inositol, particularly when combined with selenium, has been proven to improve thyroid hormone profiles while also lowering nodule size or growth. In Graves' disease, supplementation has been linked to the restoration of biochemical euthyroidism in certain patients, albeit data are limited. Despite these encouraging results, diversity in trial design, treatment length, and dosages restrict the robustness of existing recommendations. <b>Conclusions</b>: Selenium and myo-inositol supplementation have shown promise as adjuvant treatments for autoimmune thyroid diseases and benign thyroid nodules. However, further large-scale, well-designed clinical trials are needed to determine the appropriate dosages, treatment duration, and patient selection criteria. Personalized supplementation solutions may improve medication efficacy and help with more comprehensive thyroid disease care.