Different clinical autoimmune polyglandular syndrome phenotypes among patients with thyroid diseases

Purpose: To characterize and compare autoimmune comorbidity patterns and temporal dynamics in patients with Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) within an autoimmune polyglandular syndrome (APS) framework. Methods: We retrospectively analysed patients with an autoimmune thyroid disease (AITD) and at least one additional autoimmune disease fulfilling APS criteria, followed at a tertiary APS referral centre between 2000 and 2025. The prevalence of associated autoimmune diseases was compared between HT and GD. Time to development of subsequent autoimmune diseases was assessed using Kaplan–Meier analysis and Cox proportional hazards models, with adjustment for sex and age. Results: A total of 1,057 patients (76% women; mean age 53.7 ± 16.4 years) were included, of whom 964 had HT and 93 GD. Type 1 diabetes was the most frequent autoimmune comorbidity, but was significantly less prevalent in GD than in HT (OR 0.48, 95% CI 0.31–0.75; FDR-adjusted p = 0.008). GD was selectively enriched for systemic sclerosis (OR 51.54, 95% CI 10.96–242.41; FDR-adjusted p < 0.001) and vitiligo (OR 3.46, 95% CI 1.82–6.55; FDR-adjusted p < 0.001). In patients in whom AITD was the first autoimmune manifestation (n = 333), GD was associated with a longer latency to additional autoimmune diseases and a lower hazard of subsequent autoimmunity compared with HT (HR 0.52, 95% CI 0.37–0.73; p < 0.001). Conclusion: Within APS-related AITD, HT and GD anchor distinct autoimmune phenotypes with different clustering patterns and temporal trajectories. These differences have relevant clinical implications for risk stratification and personalized surveillance of patients with autoimmune thyroid disease.