Potential mechanisms involve: (1) impaired enzymatic efficiency due to the Thr92Ala DIO2 polymorphism at low FT4/FT3 ratios, whereas DIO2 overexpression under high-T4 conditions depletes essential cofactors (e.g., glutathione), thereby exacerbating T4-to-T3 conversion failure (47); (2) pro-inflammatory cytokines (TNF-α, IL-6) suppressing deiodinase activity through NF-κB-mediated downregulation of DIO1 and DIO2 expression, impairing T3 generation and promoting thyroid hormone resistance during chronic inflammation (48). This evidence concerns the gene NFKB1 and inflammatory response.