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Observational Study
. 2025 Oct 16;110(11):e3768-e3773.
doi: 10.1210/clinem/dgaf144.

Clinical Phenotype of Graves Disease in Autoimmune Polyglandular Syndrome or as Isolated Disease: The GRAPHE Study

Elisa Gatta  1   2 , Ilenia Pirola  1   2 , Aurora Gotti  1 , Micaela Fredi  3 , Pietro Bellini  4 , Francesco Dondi  4 , Riccardo Morandi  2   5 , Claudio Casella  2   5 , Francesco Bertagna  2   4 , Franco Franceschini  3 , Mario Rotondi  6   7 , Carlo Cappelli  1   2
Affiliations
Observational Study

Clinical Phenotype of Graves Disease in Autoimmune Polyglandular Syndrome or as Isolated Disease: The GRAPHE Study

Elisa Gatta et al. J Clin Endocrinol Metab. .

Abstract

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.

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

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Figures

Figure 1.
Figure 1.
Prevalence of the various autoimmune conditions associated with GD in the APS group.
See this image and copyright information in PMC

References

    1. Wémeau JL, Klein M, Sadoul JL, Briet C, Vélayoudom-Céphise FL. Graves’ disease: introduction, epidemiology, endogenous and environmental pathogenic factors. Ann Endocrinol (Paris). 2018;79(6):599‐607. - PubMed
    1. Brent GA. Clinical practice. Graves’ disease. N Engl J Med. 2008;358(24):2594‐2605. - PubMed
    1. Smith TJ, Hegedüs L. Graves’ disease. N Engl J Med. 2016;375(16):1552‐1565. - PubMed
    1. Hussain YS, Hookham JC, Allahabadia A, Balasubramanian SP. Epidemiology, management and outcomes of Graves’ disease-real life data. Endocrine. 2017;56(3):568‐578. - PMC - PubMed
    1. Adams DD, Fastier FN, Howie JB, Kennedy TH, Kilpatrick JA, Stewart RD. Stimulation of the human thyroid by infusions of plasma containing LATS protector. J Clin Endocrinol Metab. 1974;39(5):826‐832. - PubMed

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