Radioactive iodine (RAI) therapy is an effective treatment for hyperthyroidism, particularly Graves’ disease and toxic adenoma. Although its efficacy in normalizing thyroid hormone levels is well-established, predictive biomarkers for long-term metabolic effects remain underexplored.

Aim. To examine post-RAI metabolic changes and assess the predictive value of baseline TSH and metabolic indices for metabolic risk in patients with Graves’ disease and toxic adenoma.

Materials and methods. This prospective study included 83 patients (Graves’ disease, n = 62; toxic adenoma, n = 21), aged 25–65 years, who underwent RAI therapy. Participants were stratified by pre-treatment TSH levels: Group A (≤0.01 mIU/L) and Group B (>0.01 mIU/L). Metabolic parameters (glucose, insulin, HOMA-IR, leptin, TyG index, lipid profile, and BMI) were assessed before and 12 months after treatment. Statistical analyses included Mann–Whitney U and Wilcoxon signed-rank test, and ROC curve analysis.

Results. Group A, with suppressed baseline TSH, exhibited significantly higher post-treatment insulin resistance (HOMA-IR: 4.77 vs. 3.09, p < 0.001), fasting insulin (p < 0.001), TyG index (p = 0.005), and fasting glucose (p = 0.006), despite comparable BMI between groups. Leptin levels were higher in Group A but not statistically significant. Wilcoxon tests revealed significant improvements in hormonal and metabolic parameters in both groups. ROC analysis identified LDL (AUC = 0.662, p = 0.027) and HDL (AUC = 0.665, p = 0.024) as significant predictors of metabolic outcomes, while leptin showed borderline significance (AUC = 0.631, p = 0.074).

Conclusions. RAI treatment in hyperthyroid patients is associated with substantial metabolic changes, particularly in those with suppressed pre-treatment TSH levels. Insulin resistance and adipokine dysregulation are more pronounced in this subgroup, with LDL and HDL values identified as significant post-RAI metabolic predictors. These findings underscore the need for metabolic risk stratification and targeted follow-up in patients undergoing RAI therapy.