title: Pregnancy, Primary Aldosteronism, and Adrenal CTNNB1 Mutations.
abstract: Recent discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas with distinct clinical presentations and pathological features. Here we describe three women with hyperaldosteronism, two who presented in pregnancy and one who presented after menopause. Their aldosterone-producing adenomas harbored activating mutations of CTNNB1, encoding β-catenin in the Wnt cell-differentiation pathway, and expressed LHCGR and GNRHR, encoding gonadal receptors, at levels that were more than 100 times as high as the levels in other aldosterone-producing adenomas. The mutations stimulate Wnt activation and cause adrenocortical cells to de-differentiate toward their common adrenal-gonadal precursor cell type. (Funded by grants from the National Institute for Health Research Cambridge Biomedical Research Centre and others.).
authors.affiliation: From the Clinical Pharmacology Unit, Centre for Clinical Investigation, Addenbrooke's Hospital, University of Cambridge (A.E.D.T., S.G., L.H.S., J.Z., E.A.B.A., M.J.B.), Department of Medical Genetics, Division of Renal Medicine, University of Cambridge (F.E.K.F.), University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council (MRC) Institute of Metabolic Science, Addenbrooke's Hospital (M.G.), Department of Pathology, Addenbrooke's Hospital (L.H., A.M.), and MRC Laboratory of Molecular Biology (M.B.) - all in Cambridge, United Kingdom; and the Department of Medicine, National University of Malaysia Medical Centre, Kuala Lumpur (E.A.B.A.).
authors.forename: Ada E D
authors.initials: AE
authors.lastname: Teo
authors.forename: Sumedha
authors.initials: S
authors.lastname: Garg
authors.forename: Lalarukh Haris
authors.initials: LH
authors.lastname: Shaikh
authors.forename: Junhua
authors.initials: J
authors.lastname: Zhou
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Karet Frankl
authors.forename: Mark
authors.initials: M
authors.lastname: Gurnell
authors.forename: Lisa
authors.initials: L
authors.lastname: Happerfield
authors.forename: Alison
authors.initials: A
authors.lastname: Marker
authors.forename: Mariann
authors.initials: M
authors.lastname: Bienz
authors.forename: Elena A B
authors.initials: EA
authors.lastname: Azizan
authors.forename: Morris J
authors.initials: MJ
authors.lastname: Brown
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000450:Aldosterone / Q000378:metabolism; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000209:etiology*; D006973:Hypertension / Q000209:etiology; D007008:Hypokalemia / Q000209:etiology; D008875:Middle Aged; D017698:Postmenopause; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000235:genetics*; D011974:Receptors, LH / Q000378:metabolism; D011966:Receptors, LHRH / Q000378:metabolism; D015854:Up-Regulation; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D011974:Receptors, LH; D011966:Receptors, LHRH; D051176:beta Catenin; D000450:Aldosterone