Pregnancy, Primary Aldosteronism and Somatic CTNNB1 Mutations in the Adrenal
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Authors
Garg, Sumedha
Shaikh, Lalarukh Haris
Zhou, Junhua
Karet, Fiona https://orcid.org/0000-0002-2457-2869
Abstract
Recent discoveries of somatic mutations permit the recognition of sub-types of aldosterone-producing adenomas (APA) with different clinical presentations and pathology. Here we describe two women who presented in pregnancy, and one woman who presented post-menopause, with hyperaldosteronism. Their APAs harbored activating mutations of CTNNB1, encoding β-catenin in the Wnt cell-differentiation pathway, and expressed >100-fold higher levels of LHCGR and GNRHR, encoding gonadal receptors, than other APAs. The mutations stimulate Wnt activation and cause adrenocortical cells to de-differentiate towards their common gonad-adrenal precursor cell-type.
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Keywords
Journal Title
New England Journal of Medicine
Conference Name
Journal ISSN
0028-4793
1533-4406
1533-4406
Volume Title
373
Publisher
Massachusetts Medical Society
Publisher DOI
Sponsorship
Wellcome Trust (085686/Z/08/A)
British Heart Foundation (FS/11/35/28871)
British Heart Foundation (FS/14/75/31134)
MRC (MR/K501050/1)
Wellcome Trust (100140/Z/12/Z)
British Heart Foundation (PG/07/085/23349)
British Heart Foundation (SP/08/002/24118)
British Heart Foundation (FS/14/12/30540)
British Heart Foundation (FS/11/35/28871)
British Heart Foundation (FS/14/75/31134)
MRC (MR/K501050/1)
Wellcome Trust (100140/Z/12/Z)
British Heart Foundation (PG/07/085/23349)
British Heart Foundation (SP/08/002/24118)
British Heart Foundation (FS/14/12/30540)
AEDT is supported by Agency for Science, Technology and Research (A*STAR) Singapore and the Wellcome Trust (085686/Z/08/A); SG and LHS are supported by the British Heart Foundation (FS/14/75/31134; FS/11/35/28871); EABA was supported by the Tunku Abdul Rahman Centenary Fund (St Catharine's College, Cambridge, UK) and the Austin Doyle Award (Servier Australia). JZ was supported by the Cambridge Overseas Trust Scholarship. MG is supported by the NIHR Cambridge Biomedical Research Centre (Metabolic), and MB is supported by the MRC (U105192713). The work was funded by the NIHR Cambridge Biomedical Research Centre (Cardiovascular) and an NIHR Senior Investigator award (NF-SI-0512-10052) to MJB.