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

Abstract

Context: Graves' disease 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 two forms.

Objective: To assess differences in clinical presentation, complications, and outcomes in patients with isolated Graves' disease compared to those in whom Graves' disease is part of an autoimmune polyglandular syndrome.

Methods: GRAPHE study is a retrospective observational study. The medical records of all patients with Graves' disease 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: 567 patients (77% women) were enrolled. The patients were divided into three different groups based of Graves' disease phenotypes: subjects affected by isolated Graves' disease (Isolated GD); patients that developed autoimmune polyglandular syndrome (GD1-APS), and patients with autoimmune polyglandular syndrome that developed Graves' disease during follow-up (GD2-APS). The three groups were superimposable for gender (p = 0.086), fT4 (p=0.899), fT3 (p=0.434), TRAb titers (p = 0.882), and thyroid volume (p=0.840) at disease onset. Isolated GD patients exhibited Graves' orbitopathy more frequently (p<0.001), a higher rate of definitive therapy (p<0.001) and shorter time between disease onset and definitive therapy (p<0.001) compared to the GD1-APS and GD2-APS patients.

Conclusions: 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.

Keywords: Graves’ disease; autoimmune diseases; autoimmune polyglandular syndrome.