title: The prevalence of CTNNB1 mutations in primary aldosteronism and consequences for clinical outcomes.
abstract: Constitutive activation of the Wnt pathway/β-catenin signaling may be important in aldosterone-producing adenoma (APA). However, significant gaps remain in our understanding of the prevalence and clinical outcomes after adrenalectomy in APA patients harboring CTNNB1 mutations. The molecular expression of CYP11B2 and gonadal receptors in adenomas were also explored. Adenomas from 219 APA patients (95 men; 44.2%; aged 50.5 ± 11.9 years) showed a high rate of somatic mutations (n = 128, 58.4%). The majority of them harbored KCNJ5 mutations (n = 116, 52.9%); 8 patients (3.7%, 6 women) had CTNNB1 mutations. Patients with APAs harboring CTNNB1 mutations were older and had shorter duration of hypertension. After adrenalectomy, CTNNB1 mutation carriers had a higher possibility (87.5%) of residual hypertension than other APA patients. APAs harboring CTNNB1 mutations have heterogeneous staining of β-catenin and variable expression of gonadal receptors and both CYP11B1 and CYP11B2. This suggests that CTNNB1 mutations may be more related to tumorigenesis rather than excessive aldosterone production.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Vin-Cent
authors.initials: VC
authors.lastname: Wu
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Shuo-Meng
authors.initials: SM
authors.lastname: Wang
authors.affiliation: Cleveland Clinic Lerner College of Medicine and Glickman Urological and Kidney Institute, Cleveland Clinic, USA.
authors.forename: Shih-Chieh Jeff
authors.initials: SJ
authors.lastname: Chueh
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|TAIPAI, Taiwan Primary Aldosteronism investigator, Taipei, Taiwan.
authors.forename: Shao-Yu
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Department of Urology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Kuo-How
authors.initials: KH
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yen-Hung
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan City, Taiwan.
authors.forename: Jian-Jhong
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: EKF Diagnostics, Cardiff, Wales, UK.
authors.forename: Rory
authors.initials: R
authors.lastname: Connolly
authors.affiliation: Department of internal medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Hu
authors.affiliation: Division of Endocrinology, G.V. (Sonny) Montgomery VA Medical Center and Department of Medicine, The University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Celso E
authors.initials: CE
authors.lastname: Gomez-Sanchez
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Kang-Yung
authors.initials: KY
authors.lastname: Peng
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|TAIPAI, Taiwan Primary Aldosteronism investigator, Taipei, Taiwan.
authors.forename: Kwan-Dun
authors.initials: KD
authors.lastname: Wu
mesh_terms: D000315:Adrenalectomy; D019405:Cytochrome P-450 CYP11B2 / Q000032:analysis / Q000235:genetics; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D006973:Hypertension / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D016896:Treatment Outcome; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D051176:beta Catenin; D019405:Cytochrome P-450 CYP11B2