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Annelies van’t Westeinde Department of Women’s and Children’s Health, Karolinska Institutet and Division of Pediatrics, Unit for Pediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, Stockholm, Sweden

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Leif Karlsson Department of Women’s and Children’s Health, Karolinska Institutet and Division of Pediatrics, Unit for Pediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, Stockholm, Sweden

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Valeria Messina Department of Women’s and Children’s Health, Karolinska Institutet and Division of Pediatrics, Unit for Pediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, Stockholm, Sweden

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Lena Wallensteen Department of Women’s and Children’s Health, Karolinska Institutet and Division of Pediatrics, Unit for Pediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, Stockholm, Sweden

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Manuela Brösamle European Patient Advocacy Group for Adrenal Diseases, European Reference Network on Rare Endocrine Conditions (Endo ERN), Endo ERN Coordinating Centre, Leiden, The Netherlands

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Giorgio Dal Maso ArfSAG (Associazione Refionale Famiglie Sindrome Adreno Genitale) c/o Unita Operativa di Pediatria, Azienda Ospedaliero Universitaria di Bologna, Policlinico S Orsala-Malpighi, Bologna, Italy

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Alessandro Lazzerini Spanish Association of Congenital Adrenal Hyperplasia (CAH), Spain

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Jette Kristensen ePAG & Chair of Danish Addison Patient Association, Aarhus, Denmark

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Diana Kwast Dutch Adrenal Society NVACP, Nijkerk, The Netherlands

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Lea Tschaidse Department of Endocrinology, Medizinische Klinik IV, Klinikum der Universität München, Munich, Germany

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Matthias K Auer Department of Endocrinology, Medizinische Klinik IV, Klinikum der Universität München, Munich, Germany

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Hanna F Nowotny Department of Endocrinology, Medizinische Klinik IV, Klinikum der Universität München, Munich, Germany

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Luca Persani Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Nicole Reisch Department of Endocrinology, Medizinische Klinik IV, Klinikum der Universität München, Munich, Germany

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Svetlana Lajic Department of Women’s and Children’s Health, Karolinska Institutet and Division of Pediatrics, Unit for Pediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, Stockholm, Sweden

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, which is required for the conversion of cholesterol to cortisol and aldosterone, rendering it either partly or completely ineffective ( 2 , 3 ). Patients with classic CAH, therefore, experience glucocorticoid (GC) and mineralocorticoid deficiency

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Marianna Viukari Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

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Helena Leijon Department of Pathology, University of Helsinki and HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland

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Tiina Vesterinen Department of Pathology, University of Helsinki and HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland

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Sanni Söderlund Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

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Päivi Hämäläinen Department of Internal Medicine, Tampere University Hospital, Tampere, Finland

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Iina Yliaska Medical Research Center Oulu, Oulu University Hospital and Research Unit of Internal Medicine, University of Oulu, Oulu, Finland

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Päivi Rautiainen Joint Municipal Authority for North Karelia Social and Health Services (Siun Sote), Joensuu, Finland

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Reeta Rintamäki Department of Endocrinology and Clinical Nutrition, Kuopio University Hospital, Kuopio, Finland

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Minna Soinio Department of Endocrinology, Turku University Hospital, Turku, Finland

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Ilkka Pörsti Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland

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Pasi I Nevalainen Department of Internal Medicine, Tampere University Hospital, Tampere, Finland

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Niina Matikainen Endocrinology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

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performed during continuous 50 µg/h cosyntropin infusion. Catheterization was considered successful when the selectivity index (SI = AV/inferior vena cava (IVC) cortisol concentrations) on both sides is ≥5. PA was classified as unilateral based on a

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Tomaž Kocjan Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

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Gaj Vidmar Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
University Rehabilitation Institute, Ljubljana, Slovenia
FAMNIT, University of Primorska, Koper, Slovenia

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Peter Popović Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia

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Milenko Stanković Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia

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selectivity index (SI), determined as the ratio of concentrations of cortisol from an adrenal vein and the infra-adrenal inferior vena cava (IVC), was at least 5 on both sides ( 28 , 29 ). Lateralization index (LI) was calculated as the gradient of the higher

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Rachel Forfar Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Mashal Hussain Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK

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Puneet Khurana Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Jennifer Cook Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Steve Lewis Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Dillon Popat Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK

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David Jackson Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK

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Ed McIver Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Jeff Jerman Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Debra Taylor Centre for Therapeutics Discovery, LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, UK

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Adrian JL Clark Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK

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Li F Chan Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, UK

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vasopressin. ACTH then acts on the adrenal glands to produce glucocorticoids and cortisol in humans. Cortisol negatively feeds back at the level of the pituitary gland and hypothalamus to inhibit further production and release ACTH. The melanocortins act

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Sriharsha Gunna Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Mahaveer Singh Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Rakesh Pandey Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Rungmei S K Marak Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Amita Aggarwal Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Bibhuti Mohanta Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Liping Yu Barbara Davis Centre for Diabetes, School of Medicine University of Colorado, Aurora, Colorado, USA

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Eesh Bhatia Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Primary adrenal insufficiency (PAI) or Addison’s disease is an uncommon disorder resulting from deficiency of cortisol and aldosterone due to the destruction of adrenal cortices ( 1 , 2 ). Early diagnosis and prompt institution of treatment is

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Natacha Driessens Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Madhu Prasai Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Orsalia Alexopoulou Department of Endocrinology, Cliniques Universitaires Saint Luc, Brussels, Belgium

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Christophe De Block Department of Endocrinology-Diabetology-Metabolism, Universitair Ziekenhuis Antwerpen & University of Antwerp, Drie Eikenstraat, Edegem, Belgium

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Eva Van Caenegem Department of Endocrinology, Academisch Ziekenhuis Sint-Jan Brugge – Oostende AV, Ruddershove, Brugge, Belgium

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Guy T’Sjoen Department of Endocrinology, Ghent Universitary Hospital, C. Heymanslaan, Gent, Belgium

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Frank Nobels Department of Endocrinology, Onze-Lieve Vrouw Ziekenhuis, Moorselbaan, Aalst, Belgium

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Christophe Ghys Department of Endocrinology, Universitair Ziekenhuis Brussel, Laarbeeklaan, Brussels, Belgium

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Laurent Vroonen Department of Endocrinology, Cliniques Universitaires de Liège, Avenue de l’hôpital, Liège, Belgium

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Corinne Jonas Department of Endocrinology, CHU UCL Namur - Godinne, Avenue Docteur Gaston Thérasse, Yvoir, Belgium

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Bernard Corvilain Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Dominique Maiter Department of Endocrinology, Cliniques Universitaires Saint Luc, Brussels, Belgium

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criteria: (i) a simultaneous serum level cortisol below and a plasma ACTH 2-fold above reference ranges; (ii) a high plasma ACTH concentration with a failed cortisol response (<400 nmol/L) to 250 µg intravenous ACTH injection and/or (iii) chronic treatment

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Sofia Maria Lider Burciulescu University of Medicine and Pharmacy Carol Davila Bucharest, Bucharest, Romania
National Institute of Endocrinology CI Parhon, Bucharest, Romania

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Monica Livia Gheorghiu University of Medicine and Pharmacy Carol Davila Bucharest, Bucharest, Romania
National Institute of Endocrinology CI Parhon, Bucharest, Romania

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Andrei Muresan National Institute of Endocrinology CI Parhon, Bucharest, Romania

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Iuliana Gherlan University of Medicine and Pharmacy Carol Davila Bucharest, Bucharest, Romania
National Institute of Endocrinology CI Parhon, Bucharest, Romania

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Attila Patocs Department of Laboratory Medicine and Molecular Genetics, Clinical Genetics and Endocrinology Laboratory, Semmelweis University National Institute of Oncology, Budapest, Hungary

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Corin Badiu University of Medicine and Pharmacy Carol Davila Bucharest, Bucharest, Romania
National Institute of Endocrinology CI Parhon, Bucharest, Romania

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metastatic disease were CT scans and MRIs. The presence of AI was defined as low morning (08:00–09.00 h) cortisol level (<3 µg/dL) and insufficient cortisol response to a stimulation (Synachten) test at a maximum 1 month post surgery and the need of gluco

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Paola Parra Ramírez Endocrinology & Nutrition Department, La Paz University Hospital, Madrid, Spain

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Patricia Martín Rojas-Marcos Endocrinology & Nutrition Department, La Paz University Hospital, Madrid, Spain

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Miguel Paja Fano Endocrinology & Nutrition Department, Hospital Universitario de Basurto, Bilbao, Spain
Medicine Department, Basque Country University, Bilbao, Spain

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Marga González Boillos Endocrinology & Nutrition Department, Hospital Universitario de Castellón, Castellón, Spain

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Eider Pascual-Corrales Endocrinology & Nutrition Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain

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Ana García-Cano Biochemistry Department, Hospital Universitario Ramón y Cajal, Madrid, Spain

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Jorge Gabriel Ruiz-Sanchez Endocrinology & Nutrition Department, Hospital Fundación Jiménez Díaz, Madrid, Spain

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Almudena Vicente Endocrinology & Nutrition Department, Complejo Universitario de Toledo, Toledo, Spain

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Emilia Gómez-Hoyos Endocrinology & Nutrition Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain

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Rui Ferreira Endocrinology & Nutrition Department, Hospital Universitario de La Princesa, Madrid, Spain

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Iñigo García Sanz General & Digestive Surgery Department, Hospital Universitario de La Princesa, Madrid, Spain

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Mònica Recasens Endocrinology & Nutrition Department, Hospital Josep Trueta, Servei d’Endocrinologia, Girona, Spain

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Begoña Pla Peris Endocrinology & Nutrition Department, Hospital Universitario de Castellón, Castellón, Spain

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Rebeca Barahona San Millan Endocrinology & Nutrition Department, Hospital Josep Trueta, Servei d’Endocrinologia, Girona, Spain

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María José Picón César Endocrinology & Nutrition Department, Complejo Hospitalario Málaga (Hospital Virgen de la Victoria), IBIMA Malaga, Malaga, Spain
CIBEROBN, Madrid, Spain

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Patricia Díaz Guardiola Endocrinology & Nutrition Department, Hospital Universitario Infanta Sofía, Madrid, Spain

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Juan Jesús García González Endocrinology & Nutrition Department, Hospital Universitario Virgen de la Macarena, Sevilla, Spain

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Carolina Perdomo Endocrinology & Nutrition Department, Clínica Universidad de Navarra, Pamplona, Spain

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Laura Manjón Endocrinology & Nutrition Department, Hospital Universitario Central de Asturias, Oviedo, Spain
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain

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Rogelio García-Centeno Endocrinology & Nutrition Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Juan Carlos Percovich Endocrinology & Nutrition Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Ángel Rebollo Román Endocrinology & Nutrition Department, Hospital Reina Sofía, Córdoba, Spain

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Paola Gracia Gimeno Endocrinology & Nutrition Department, Hospital Royo Villanova, Zaragoza, Spain

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Cristina Robles Lázaro Endocrinology & Nutrition Department, Hospital Universitario de Salamanca, Salamanca, Spain

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Manuel Morales Biochemistry and Molecular Genetics Department-CDB, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain

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Felicia Hanzu Endocrinology & Nutrition Department, Hospital Clinic, Barcelona, Spain

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Marta Araujo-Castro Endocrinology & Nutrition Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Madrid, Spain
University of Alcalá, Madrid, Spain

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) in whom PA (normal plasma aldosterone (PAC)/renin ratio) and glucocorticoid excess (cortisol post-dexamethasone suppression test <1.8 µg/dL) was excluded, were included as control groups. Two control groups were established: one group <65 years old

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Supitcha Patjamontri Developmental Endocrinology Research Group, University of Glasgow, Royal Hospital for Children, Glasgow, UK
Division of Endocrinology and Metabolism, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

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Alexander Spiers MRC Centre for Environment and Health, Imperial College London, London, UK
NIHR Health Protection Research Unit on Chemical Radiation Threats and Hazards, Imperial College London, London, UK

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Rachel B Smith MRC Centre for Environment and Health, Imperial College London, London, UK
NIHR Health Protection Research Unit on Chemical Radiation Threats and Hazards, Imperial College London, London, UK
National Institute for Health Research (NIHR) Health Protection Research Unit in Environmental Exposures and Health, Imperial College London, London, UK
Mohn Centre for Children’s Health and Wellbeing, Imperial College London, London, UK

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Chen Shen MRC Centre for Environment and Health, Imperial College London, London, UK
NIHR Health Protection Research Unit on Chemical Radiation Threats and Hazards, Imperial College London, London, UK

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Jo Adaway Department of Clinical Biochemistry, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK

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Brian G Keevil Department of Clinical Biochemistry, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK

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Mireille B Toledano MRC Centre for Environment and Health, Imperial College London, London, UK
NIHR Health Protection Research Unit on Chemical Radiation Threats and Hazards, Imperial College London, London, UK
National Institute for Health Research (NIHR) Health Protection Research Unit in Environmental Exposures and Health, Imperial College London, London, UK
Mohn Centre for Children’s Health and Wellbeing, Imperial College London, London, UK

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S Faisal Ahmed Developmental Endocrinology Research Group, University of Glasgow, Royal Hospital for Children, Glasgow, UK

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Software 2021 98 1 – 27 . ( https://doi.org/10.18637/jss.v098.i11 ) 34 Harden KP Wrzus C Luong G Grotzinger A Bajbouj M Rauers A Wagner GG & Riediger M . Diurnal coupling between testosterone and cortisol from adolescence to older

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Simone Martins de Castro Hospital Materno Infantil Presidente Vargas, Newborn Screening Referral Center, Porto Alegre, RS, Brazil
Department of Analysis, Universidade Federal do Rio Grande do Sul (UFRGS), School of Pharmacy, Porto Alegre, RS, Brazil

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Paloma Wiest Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil

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Poli Mara Spritzer Division of Endocrinology, Department of Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil

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Cristiane Kopacek Hospital Materno Infantil Presidente Vargas, Newborn Screening Referral Center, Porto Alegre, RS, Brazil
Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
Department of Pediatrics, Universidade Federal do Rio Grande do Sul (UFRGS), Medical School, Porto Alegre, RS, Brazil

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Introduction Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder characterized by inadequate cortisol secretion (with or without insufficient aldosterone production) and androgen excess, caused by deficiency in one of the

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