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Endocrine Abstracts (2024) 99 EP736 | DOI: 10.1530/endoabs.99.EP736

ECE2024 Eposter Presentations Adrenal and Cardiovascular Endocrinology (155 abstracts)

Polygenic risk score for autoimmune Addison’s disease combined with whole-genome sequencing identifies patients with undiagnosed monogenic primary adrenal insufficiency

Maribel Aranda-Guillen 1 , Ileana R. Botusan 1,2 , Venuja Fernando 1 , Ellen Røyrvik 3,4,5 , Anette Susanne Bøe Wolff 3,4,6 , Stefan Johansson 3,7 , Eystein Sverre Husebye 1,3,4,6 , Sophie Bensing 2,8 , Olle Kämpe 1,2 & Daniel Eriksson 1,9


1Karolinska Institutet, Center for Molecular Medicine, Department of Medicine, Solna, Stockholm, Sweden; 2Karolinska University Hospital, Department of Endocrinology, Stockholm, Sweden; 3University of Bergen, Department of Clinical Science, Bergen, Norway; 4K.G. Jebsen Center for Autoimmune Disorders, Bergen, Norway; 5Norwegian Institute of Public Health, Department of Genetics and Bioinformatics, Bergen, Norway; 6Haukeland University Hospital, Department of Medicine, Bergen, Norway; 7Haukeland University Hospital, Department of Medical Genetics, Bergen, Norway; 8Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; 9Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala, Sweden


Background: Primary adrenal insufficiency (PAI) is sometimes misdiagnosed as autoimmune Addison’s disease (AAD), affecting clinical management and genetic counselling. We tested a polygenic risk score (PRS) for AAD (PRS14AAD) as a tool to reevaluate disease etiology and identify patients misdiagnosed with AAD.

Methods: We calculated the PRS14AAD in a cohort of patients diagnosed with AAD but lacking 21-hydroxylase autoantibodies (n=124). Patients with low genetic susceptibility to AAD were selected for whole-genome sequencing to detect potential monogenic causes (n=35).

Results: Among the 35 patients, monogenic PAI was found in 5 (14%) and suspected in 3 additional cases (9%). Three out of the 5 rediagnosed patients developed the disease in adulthood, indicating late-onset monogenic disease associated with hypomorphic genetic variants.

Conclusion: A PRS for AAD can help identify potential monogenic cases, regardless of the age at diagnosis. Early identification of the underlying cause of PAI enables accurate management and correct genetic counselling

Volume 99

26th European Congress of Endocrinology

Stockholm, Sweden
11 May 2024 - 14 May 2024

European Society of Endocrinology 

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