Coexistence of Congenital Adrenal Hyperplasia and Autoimmune Addison's Disease

Sigrid Aslaksen; Paal Methlie; Magnus D Vigeland; Dag E Jøssang; Anette B Wolff; Ying Sheng; Bergithe E Oftedal; Beate Skinningsrud; Dag E Undlien; Kaja K Selmer; Eystein S Husebye; Eirik Bratland

doi:10.3389/fendo.2019.00648

Coexistence of Congenital Adrenal Hyperplasia and Autoimmune Addison's Disease

Front Endocrinol (Lausanne). 2019 Sep 27:10:648. doi: 10.3389/fendo.2019.00648. eCollection 2019.

Authors

Sigrid Aslaksen^{1

2}, Paal Methlie^{1

2

3}, Magnus D Vigeland^{4

5}, Dag E Jøssang⁶, Anette B Wolff^{1

2}, Ying Sheng⁵, Bergithe E Oftedal^{1

2}, Beate Skinningsrud⁵, Dag E Undlien^{4

5}, Kaja K Selmer^{7

8}, Eystein S Husebye^{1

2

3}, Eirik Bratland^{1

2}

Affiliations

¹ Department of Clinical Science, University of Bergen, Bergen, Norway.
² K.G. Jebsen Center for Autoimmune Diseases, University of Bergen, Bergen, Norway.
³ Department of Medicine, Haukeland University Hospital, Bergen, Norway.
⁴ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁵ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
⁶ Department of Radiology, Haukeland University Hospital, Bergen, Norway.
⁷ Division of Clinical Neuroscience, Department of Research and Development, Oslo University Hospital, University of Oslo, Oslo, Norway.
⁸ National Centre for Epilepsy, Oslo University Hospital, Oslo, Norway.

Abstract

Background: Underlying causes of adrenal insufficiency include congenital adrenal hyperplasia (CAH) and autoimmune adrenocortical destruction leading to autoimmune Addison's disease (AAD). Here, we report a patient with a homozygous stop-gain mutation in 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2), in addition to impaired steroidogenesis due to AAD. Case Report: Whole exome sequencing revealed an extremely rare homozygous nonsense mutation in exon 2 of the HSD3B2 gene, leading to a premature stop codon (NM_000198.3: c.15C>A, p.Cys5Ter) in a patient with AAD and premature ovarian insufficiency. Scrutiny of old medical records revealed that the patient was initially diagnosed with CAH with hyperandrogenism and severe salt-wasting shortly after birth. However, the current steroid profile show complete adrenal insufficiency including low production of pregnenolone, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S), without signs of overtreatment with steroids. Conclusion: To the best of our knowledge, this is the first description of autoimmune adrenalitis in a patient with 3βHSD2 deficiency and suggests a possible association between AAD and inborn errors of the steroidogenesis.

Keywords: 3β-hydroxysteroid dehydrogenase type 2 deficiency; adrenal insufficiency; autoimmune Addison's disease; autoimmune adrenalitis; congenital adrenal hyperplasia.

Publication types

Case Reports