Myo-Inositol Plus Selenium vs. Selenium Alone in Hashimoto’s Thyroiditis with Subclinical Hypothyroidism: A Systematic Review and Updated Meta-Analysis with Trial Sequential Analysis

Introduction: Hashimoto’s thyroiditis (HT) is the leading cause of hypothyroidism in iodine-sufficient regions and often presents with subclinical hypothyroidism. Selenium (Sel) has immunomodulatory effects, while myo-inositol (MI) may enhance thyroid-stimulating hormone (TSH) signaling. This study evaluated whether adding myo-inositol to selenium provides additional benefit compared with selenium alone in these patients. Methods: A systematic search of PubMed, Web of Science, and the Cochrane Library was conducted from inception to 7 March 2026. Studies comparing myo-inositol plus selenium (MI + Sel) with Sel monotherapy were included. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a frequentist random-effects model. Outcomes of interest included TSH, free T3 and T4, thyroglobulin antibodies (TgAb), and thyroid peroxidase antibodies (TPOAb). Trial sequential analysis (TSA) was performed to assess the robustness of significant findings. Results: Three studies involving 288 patients were included (151 receiving MI + Sel and 137 receiving Sel alone). Combination therapy significantly reduced TSH levels compared with Sel monotherapy (SMD −1.26; 95% CI −1.51 to −1.00; p < 0.01; I2 = 0%), and TSA suggested that this finding may be robust, although the evidence is limited by the small number of studies. TgAb levels were also significantly reduced (SMD −0.51; 95% CI −0.78 to −0.24; p < 0.01; I2 = 0%); however, TSA indicated a potential risk of type I error. No significant differences were observed for T3 (SMD 0.15; 95% CI −0.09 to 0.38; p = 0.22; I2 = 7%), T4 (SMD −0.01; 95% CI −0.72 to 0.69; p = 0.97; I2 = 88%), or TPOAb (SMD −0.18; 95% CI −0.44 to 0.09; p = 0.20; I2 = 0%). Conclusions: MI combined with Sel was associated with a significant reduction in TSH levels compared with Sel alone in patients with HT and subclinical hypothyroidism, suggesting a potential therapeutic benefit. However, given the limited number of studies, these findings should be interpreted with caution. Further large randomized controlled trials are required to confirm the effects on thyroid function and autoimmunity.