Clinical phenotype of Graves' disease in Autoimmune Polyglandular Syndrome or as isolated disease: the GRAPHE study

Context Graves disease (GD) can occur as an isolated condition or as part of an autoimmune polyglandular syndrome; there are no data regarding the differences in phenotype between these 2 forms. Objective To assess differences in clinical presentation, complications, and outcomes in patients with isolated GD compared to those in whom GD is part of an autoimmune polyglandular syndrome. Methods The GRAPHE study is a retrospective observational study. The medical records of all patients with GD diagnosed and regularly followed at outpatient clinics for Endocrinology, Nuclear Medicine and Clinical Surgery, from January 1, 2010, to June 30, 2024, were retrieved. All the patients were followed by the same endocrinologists and treated in accordance with existing guidelines. Results The enrolled patients (n = 567; 77% women) were divided into 3 different groups based on GD phenotypes: subjects affected by isolated GD (isolated GD); patients who developed autoimmune polyglandular syndrome (GD1-APS); and patients with autoimmune polyglandular syndrome who developed GD during follow-up (GD2-APS). The 3 groups were superimposable for gender (P = .086), fT4 (P = .899), fT3 (P = .434), TRAb titers (P = .882), and thyroid volume (P = .840) at disease onset. Isolated GD patients exhibited Graves orbitopathy more frequently (P < .001), a higher rate of definitive therapy (P < .001) and shorter time between disease onset and definitive therapy (P < .001) compared to the GD1-APS and GD2-APS patients. Conclusion The results of the present study show that, despite similar clinical and biochemical phenotype at presentation, a more severe clinical course characterizes isolated GD patients compared to those whose disease is a feature of autoimmune polyglandular syndrome.