Inflammatory Signatures of Graves’ Orbitopathy: Linking Thyroid Autoimmunity, Disease Activity, and Novel Hematological Biomarkers

Background: Graves’ disease is an autoimmune thyroid disorder that may be accompanied by systemic inflammation and Graves’ orbitopathy. This study evaluated the relationship between readily available hematological inflammatory markers and orbitopathy in patients with Graves’ disease. Methods: This retrospective observational study included 178 adult patients with Graves’ disease. Demographic, clinical, ophthalmological, and laboratory data were analyzed. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte-to-HDL cholesterol ratio (MHR), and C-reactive protein-to-albumin ratio (CAR) were calculated. Correlation, logistic regression, and ROC analyses were performed. Results: Among the 178 patients, 63 (35.4%) had Graves’ orbitopathy. Patients with orbitopathy had significantly higher NLR, PLR, SII, MHR, and CAR values than those without orbitopathy (all p < 0.001). Thyrotropin receptor antibody (TRAb) and thyroid-stimulating immunoglobulin (TSI) levels were positively correlated with all inflammatory markers. In multivariable logistic regression analysis, current smoking (OR 2.31, p = 0.047), TRAb (OR 1.08, p = 0.009), TSI (OR 1.06, p = 0.041), NLR (OR 1.63, p = 0.034), SII (OR 1.01, p = 0.018), MHR (OR 2.91, p = 0.012), and CAR (OR 3.84, p = 0.008) remained independently associated with Graves’ orbitopathy. Among the individual biomarkers, MHR showed the highest discriminative performance (AUC 0.818, 95% CI 0.754–0.882), while the combined inflammatory model achieved an AUC of 0.891 (95% CI 0.842–0.940), with an optimal predicted probability cut-off ≥ 0.43. Conclusions: Hematological inflammatory markers are associated with thyroid autoimmunity, disease activity, and Graves’ orbitopathy. These inexpensive and easily accessible markers may support clinical risk assessment in patients with Graves’ disease.