Risk factors for graves' orbitopathy: A systematic review and meta-analysis

IntroductionUnderstanding the modifiable risk factors for Graves' orbitopathy (GO) is crucial for its prevention.MethodsWe searched PubMed, Embase, and Web of Science databases following PRISMA guidelines. Studies reporting the presence of GO compared to patients with Graves' disease (GD) without orbitopathy or healthy controls were included. Statistical analysis was performed using Review Manager 5.4.1.ResultsTwenty-two studies met the inclusion criteria. Smoking increased the risk of GO, with odds ratios (ORs) of 2.00 (95% CI [1.47, 2.72]; p < 0.0001) for current smokers and 1.77 (95% CI [1.33, 2.37]; p = 0.0001) for former smokers, compared with GD patients without orbitopathy. Thyroidectomy was associated with a higher OR of Graves' disease without orbitopathy, supporting a protective effect against orbitopathy (OR 2.53; 95% CI [1.03, 6.22]; p = 0.04). However, radioiodine therapy did not show a significant association (OR 0.89; 95% CI [0.42, 1.91];p = 0.77). Biomarkers, including vitamin D (p = 0.63), FT3 (p = 0.89), FT4 (p = 0.59), and TSH (p = 0.40), showed no significant differences. In comparison to healthy controls, smoking remained a major risk factor for GO (OR 4.81; 95% CI [1.39, 16.70]; p = 0.01), while elevated FT4 (MD 8.87; 95% CI [1.64, 16.10]; p = 0.02) and decreased TSH (MD -1.23; 95% CI [-2.25, -0.20]; p = 0.02) levels were found in the GO groups.ConclusionOur analysis provides a comprehensive understanding of clinical and biomarker-based risk factors to guide targeted prevention strategies.