title: Genetic spectrum and clinical correlates of somatic mutations in aldosterone-producing adenoma.
abstract: Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D have been described in aldosterone-producing adenomas (APAs). Our aim was to investigate the prevalence of somatic mutations in these genes in unselected patients with APA (n=474), collected through the European Network for the Study of Adrenal Tumors. Correlations with clinical and biochemical parameters were first analyzed in a subset of 199 patients from a single center and then replicated in 2 additional centers. Somatic heterozygous KCNJ5 mutations were present in 38% (180/474) of APAs, whereas ATP1A1 mutations were found in 5.3% (25/474) and ATP2B3 mutations in 1.7% (8/474) of APAs. Previously reported somatic CACNA1D mutations as well as 10 novel CACNA1D mutations were identified in 44 of 474 (9.3%) APAs. There was no difference in the cellular composition of APAs or in CYP11B2, CYP11B1, KCNJ5, CACNA1D, or ATP1A1 gene expression in APAs across genotypes. Patients with KCNJ5 mutations were more frequently female, diagnosed younger, and with higher minimal plasma potassium concentrations compared with CACNA1D mutation carriers or noncarriers. CACNA1D mutations were associated with smaller adenomas. These associations were largely dependent on the population structure of the different centers. In conclusion, recurrent somatic mutations were identified in 54% of APAs. Young women with APAs are more likely to be KCNJ5 mutation carriers; identification of specific characteristics or surrogate biomarkers of mutation status may lead to targeted treatment options.
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Fabio Luiz
authors.initials: FL
authors.lastname: Fernandes-Rosa
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Tracy Ann
authors.initials: TA
authors.lastname: Williams
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Anna
authors.initials: A
authors.lastname: Riester
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Olivier
authors.initials: O
authors.lastname: Steichen
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Sheerazed
authors.initials: S
authors.lastname: Boulkroun
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Silvia
authors.initials: S
authors.lastname: Monticone
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Laurence
authors.initials: L
authors.lastname: Amar
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Tchao
authors.initials: T
authors.lastname: Meatchi
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Franco
authors.initials: F
authors.lastname: Mantero
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Maria-Verena
authors.initials: MV
authors.lastname: Cicala
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Francesco
authors.initials: F
authors.lastname: Fallo
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Bernini
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccario
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Gilberta
authors.initials: G
authors.lastname: Giacchetti
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Paolo
authors.initials: P
authors.lastname: Mulatero
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.).
authors.forename: Martin
authors.initials: M
authors.lastname: Reincke
authors.affiliation: From the INSERM, UMRS_970, Paris Cardiovascular Research Center, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); University Paris Descartes, Sorbonne Paris Cité, Paris, France (F.L.F.-R., S.B., L.A., T.M., X.J., M.-C.Z.); Service de Génétique (F.L.F.-R., X.J., M.-C.Z.), Unité Hypertension artérielle (L.A.), and Service d'Anatomie Pathologique (T.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Divisions of Internal Medicine and Hypertension, Department of Medical Sciences (T.A.W., S.M., P.M.) and Endocrinology, Diabetes, and Metabolism, Department of Medical Sciences (M.M.), University of Torino, Torino, Italy; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany (A.R., F.B., M.R.); Faculty of Medicine, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Paris, France (O.S.); Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (T.M.S.); Institute of Human Genetics, Technische Universität München, Munich, Germany (T.M.S.); Endocrine Unit, Department of Medicine (F.M., M.-V.C.) and Department of Medicine (F.F.), University of Padova, Padova, Italy; Clinical Endocrinology, Campus Mitte, University Hospital Charité, Berlin, Germany (M.Q.); Department of Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, Würzburg, Germany (B.A.); Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy (G.B.); and Division of Endocrinology, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Università Politecnica delle Marche, Ancona, Italy (G.G.). maria-christina.zennaro@inserm.fr.
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Zennaro
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D018246:Adrenocortical Adenoma / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000450:Aldosterone / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006929:Hyperaldosteronism / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics; D011188:Potassium / Q000097:blood; D012737:Sex Factors; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics
chemical_list: C472073:CACNA1D protein, human; D020746:Calcium Channels, L-Type; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D000450:Aldosterone; C499076:ATP1A1 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases; C506962:ATP2B3 protein, human; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium
keywords: adrenal cortex; aldosterone; aldosteronism; mineralocorticoids; mutation; potassium channels