Diagnostic Utility of Serum NF-κB and TNF-α in Differentiating Hashimoto’s Thyroiditis from Non-Autoimmune Hypothyroidism

Abstract

Background: Diagnosing Hashimoto’s thyroiditis (HT) relies on traditional autoantibodies, which may not fully reflect systemic inflammation. This study evaluated the diagnostic utility of serum Nuclear Factor-kappa B (NF-kB) and Tumor Necrosis Factor-alpha (TNF-α) in differentiating HT from non-autoimmune hypothyroidism. Methods: This cross-sectional study included 120 Iraqi participants: 30 with HT, 30 with non-Hashimoto hypothyroidism (Non-HT), and 60 healthy controls. Serum NF-kB and TNF-α were quantified via ELISA. Thyroid hormones and autoantibodies were measured using automated immunoassays.  Results: NF-kB and TNF-α levels were significantly elevated in the HT group compared to Non-HT and controls (p < 0.001). Both biomarkers correlated strongly with Anti-TPO, Anti-TG, and TSH. ROC analysis revealed that NF-kB possessed excellent discriminatory capacity for distinguishing HT from Non-HT (AUC = 0.95), outperforming TNF-α (AUC = 0.88). Multivariate logistic regression confirmed NF-kB as a robust independent predictor of HT (adjusted OR = 5.591; p = 0.001), even after adjusting for confounders.   Conclusion: Serum NF-kB and TNF-α are significantly elevated in HT. NF-kB demonstrates superior diagnostic performance and may serve as a valuable adjunctive biomarker for distinguishing autoimmune from non-autoimmune hypothyroidism.