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Clinical Research and Public HealthIn-Press PreviewAutoimmunityEndocrinologyGenetics Open Access | 10.1172/JCI206184

Polygenic risk score identifies alternative etiologies in misdiagnosed cases of primary adrenal insufficiency

Maribel Aranda-Guillén,1 Ileana Ruxandra Botusan,1 Venuja Fernando,1 Michela Barbaro,2 Maria Blomqvist,3 Ellen Christine Røyrvik,4 Anette Susanne Bøe Wolff,5 Eystein Sverre Husebye,1 Stephan Kemp,6 Anna Wedell,2 Olov Ekwall,7 Magnus Isaksson,8 Jeanette Wahlberg,9 Ola Lindgren,10 Jakob Skov,2 Ragnhildur Bergthorsdottir,11 Per Dahlqvist,12 Sophie Bensing,1 Olle Kämpe,13 and Daniel Eriksson13

1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

Find articles by Aranda-Guillén, M. in: PubMed | Google Scholar

1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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1Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden

2Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

3Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

4Department of Clinical Science, University of Bergen, Bergen, Norway

5Department of Biomedicine, University of Bergen, Bergen, Norway

6Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

7Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

8Department of Medical Sciences, Uppsala University, Uppsala, Sweden

9Department of Medicine, Örebro University, Örebro, Sweden

10Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden

11Department of Internal Medicine and Clinical Nutrition, Institute of Medici, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

12Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

13Center for Molecular Medicine, Department of Medicine (Solna), Karolinska Institute, Stockholm, Sweden

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Published October 22, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI206184.
Copyright © 2026, Aranda-Guillén et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published October 22, 2026 - Version history
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Abstract

BACKGROUND. Primary adrenal insufficiency (PAI) is commonly caused by autoimmunity in adults, known as autoimmune Addison’s disease (AAD). Autoantibodies against 21-hydroxylase are a hallmark of AAD but are absent in some patients diagnosed with AAD, posing a challenge to their clinical management.

METHODS. We tested a polygenic risk score for AAD (PRS14AAD) to prioritize seronegative patients for etiologic reevaluation. The PRS14AAD was calculated in patients diagnosed with AAD but lacking 21-hydroxylase autoantibodies (n = 124). Patients with low (n = 35) or high (n = 10) genetic susceptibility to AAD underwent clinical re-evaluation and whole-genome sequencing.

RESULTS. Of the 34 patients with low PRS14AAD, 14 (41%) were re-diagnosed with non-autoimmune adrenal insufficiency, whereas no alternative etiologies were identified in patients with high PRS14AAD. The low PRS group included six patients (17%) with confirmed monogenic PAI and eight patients (23%) with adrenal insufficiency due to either tuberculosis or non-primary causes. Notably, four of the six confirmed monogenic cases developed PAI in adulthood, consistent with late-onset disease caused by hypomorphic variants. Additionally, seven patients (20%) carried genetic variants suspected of causing monogenic disease.

CONCLUSION. These findings support considering genetic evaluation in patients with seronegative PAI, regardless of the age at diagnosis.

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