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Grethe Å Ueland Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway

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Thea Grinde Department of Clinical Science, University of Bergen, Bergen, Norway

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Paal Methlie Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway
K. G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway

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Oskar Kelp Department of Medicine, Akershus University Hospital, Nordbyhagen, Norway

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Kristian Løvås Department of Medicine, Haukeland University Hospital, Bergen, Norway
K. G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway

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Eystein S Husebye Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway
K. G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway

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Introduction Autonomous cortisol secretion (ACS) is usually caused by adrenal adenomas or hyperplasia and is frequently diagnosed in patients with adrenal incidentalomas (AI). AI are adrenal masses discovered on imaging undertaken for other

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Agnieszka Adamska Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Bialystok, Poland

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Vitalii Ulychnyi Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Bialystok, Poland

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Katarzyna Siewko Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Bialystok, Poland

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Anna Popławska-Kita Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Bialystok, Poland

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Małgorzata Szelachowska Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Bialystok, Poland

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Marcin Adamski Faculty of Computer Science, Bialystok University of Technology, Białystok, Poland

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Angelika Buczyńska Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland

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Adam Jacek Krętowski Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Bialystok, Poland
Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland

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incidentalomas with mild cortisol excess, when the classical clinical features of Cushing’s syndrome are not present, are defined as mild autonomous cortisol secretion (MACS) ( 6 ). It has been reported that MACS is observed in 15–50% of patients with adrenal

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Kuang Hung Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

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Bo-Ching Lee Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

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Po-Ting Chen Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

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Kao-Lang Liu Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

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Chin-Chen Chang Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
Department and Graduate Institute of Forensic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

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Vin-Cent Wu Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

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Yen-Hung Lin Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

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( 10 ) or autonomous cortisol secretion (ACS) ( 11 ). The prevalence of ACS is approximately 20% in patients with PA ( 12 , 13 ). The clinical and laboratory manifestations present as a spectrum from very low cortisol secretion, to subclinical Cushing

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

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

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

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

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

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

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

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

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

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Almudena Vicente Department of Endocrinology & Nutrition, Hospital Universitario de Toledo, Toledo, Spain

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

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Rui Ferreira Department of Endocrinology & Nutrition, Hospital Universitario Rey Juan Carlos, Madrid, Spain

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

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Mónica Recasens Department of Endocrinology & Nutrition, Institut Català de la Salut Girona, Girona, Spain

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Rebeca Barahona San Millan Department of Endocrinology & Nutrition, Institut Català de la Salut Girona, Girona, Spain

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María José Picón César Department of Endocrinology & Nutrition, Hospital Universitario Virgen de la Victoria de Málaga, IBIMA Malaga, Spain CIBEROBN, Madrid, Spain

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

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

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

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

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

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

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

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Cristina Robles Lázaro Department of Endocrinology & Nutrition, Complejo 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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María Calatayud Department of Endocrinology & Nutrition, Hospital Doce de Octubre, Madrid, Spain

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Simone Andree Furio Collao Department of Endocrinology & Nutrition, Hospital Doce de Octubre, Madrid, Spain

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Diego Meneses Department of Endocrinology & Nutrition, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain

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Miguel Antonio Sampedro Nuñez Department of Endocrinology & Nutrition, Hospital Universitario La Princesa, Madrid, Spain

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Verónica Escudero Quesada Department of Nephrology, Hospital Universitario Doctor Peser, Valencia, Spain

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Elena Mena Ribas Department of Endocrinology & Nutrition, Hospital Universitario Son Espases, Islas Baleares, Spain

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Alicia Sanmartín Sánchez Department of Endocrinology & Nutrition, Hospital Universitario Son Espases, Islas Baleares, Spain

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Cesar Gonzalvo Diaz Department of Endocrinology & Nutrition, Hospital Universitario De Albacete, Albacete, Spain

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Cristina Lamas Department of Endocrinology & Nutrition, Hospital Universitario De Albacete, Albacete, Spain

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Raquel Guerrero-Vázquez Department of Endocrinology & Nutrition, Hospital Virgen de la Macarena, Sevilla, Spain

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María del Castillo Tous Department of Endocrinology & Nutrition, Hospital Virgen de la Macarena, Sevilla, Spain

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Joaquín Serrano Department of Endocrinology & Nutrition, Hospital General Universitario de Alicante, Alicante, Spain

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Theodora Michalopoulou Department of Endocrinology and Nutrition, Joan XXIII University Hospital, Tarragona, Spain

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Eva María Moya Mateo Internal Medicine, Hospital Infanta Leonor de Vallecas, Madrid, Spain

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

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associated with increased cardiovascular morbidity and mortality compared to patients with essential hypertension (EHT) ( 2 ). On the other hand, autonomous cortisol secretion (ACS) is a well-known condition linked to a detrimental cardiometabolic profile

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Richard W Carroll Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand

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Brian Corley Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand
Department of Medicine, University of Otago, Wellington, New Zealand

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Joe Feltham Department of Radiology, Wellington Regional Hospital, New Zealand

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Patricia Whitfield Endocrine, Diabetes, and Research Centre, Wellington Regional Hospital, New Zealand
Department of Medicine, University of Otago, Wellington, New Zealand

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William Park University of Otago, Wellington, New Zealand

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Rowena Howard Diabetes and Endocrinology Service, Hutt Hospital, New Zealand

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Melissa Yssel Department of Biochemistry & Endocrinology, Awanui Labs, New Zealand

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Ian Phillips Department of Biochemistry, Awanui Labs, Dunedin, New Zealand

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Simon Harper Department of Surgery & Anaesethesia, University of Otago, Wellington, New Zealand
Department of General Surgery, Wellington Regional Hospital, New Zealand

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Jun Yang Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Victoria, Australia
Department of Medicine, Monash University, Clayton, Victoria, Australia

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sulfate (aka DHEA) has recently shown promise as a tool to detect mild autonomous cortisol secretion ( 47 ). Acknowledging the above difficulties assessing for milder forms of cortisol autonomy, the possibility of abnormal cortisol physiology in PA

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Ferdinand Roelfsema Department of Internal Medicine, Section Endocrinology, Leiden University Medical Center, Leiden, The Netherlands

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Peter Y Liu Department of Medicine, David Geffen School of Medicine at UCLA, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Los Angeles, California, USA

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Rebecca Yang Endocrine Research Unit, Mayo Clinic College of Medicine, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota, USA

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Paul Takahashi Primary Care Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA

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Johannes D Veldhuis Endocrine Research Unit, Mayo Clinic College of Medicine, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota, USA

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dependent. With advancing age, serum cortisol concentrations during the evening and early night increase, together with an advance (earlier) shift in the timing of maximal secretion ( 8 , 9 ). In addition, negative feedback inhibition of ACTH by cortisol in

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Sirazum Choudhury Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, Commonwealth Building, London, UK
Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK

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Tricia Tan Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, Commonwealth Building, London, UK
Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK

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Katharine Lazarus Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, Commonwealth Building, London, UK
Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK

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Karim Meeran Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, Commonwealth Building, London, UK
Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK

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their own potential genetic and environmental differences, it is important to note that the timing of doses was not considered in the study. Loss of diurnal rhythm in autonomous cortisol secretion also increases mortality Both autonomous cortisol

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Soraya Puglisi Internal Medicine 1, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

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Paola Perotti Internal Medicine 1, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

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Mattia Barbot Endocrinology Unit, Department of Medicine DIMED, University of Padua, Padua, Italy

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Paolo Cosio Internal Medicine 1, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

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Carla Scaroni Endocrinology Unit, Department of Medicine DIMED, University of Padua, Padua, Italy

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Antonio Stigliano Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital University of Rome, Rome, Italy

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Pina Lardo Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital University of Rome, Rome, Italy

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Valentina Morelli Endocrinology Unit, Department of Clinical Sciences and Community Health, University of Milan and Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy

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Elisa Polledri Department of Clinical Sciences and Community Health, Laboratory of Toxicology, University of Milan and Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

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Iacopo Chiodini Endocrinology Unit, Department of Clinical Sciences and Community Health, University of Milan and Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy

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Giuseppe Reimondo Internal Medicine 1, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

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Anna Pia Internal Medicine 1, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

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Massimo Terzolo Internal Medicine 1, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

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chronically suppressed by autonomous cortisol secretion, and this may ameliorate the safety profile. We hypothesized that metyrapone could be a perfectly suitable drug for a preoperative treatment of patients with ACTH-independent CS, since the fast action

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Gamze Akkuş Division of Endocrinology, Internal Medicine and Endocrinology, Cukurova University Medical Faculty, Department of Internal Medicine, Adana, Turkey

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Isa Burak Güney Nuclear Medicine Department, Cukurova University Medical Faculty, Adana, Turkey

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Fesih Ok Urology Department, Cukurova University Medical Faculty, Adana, Turkey

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Mehtap Evran Division of Endocrinology, Internal Medicine and Endocrinology, Cukurova University Medical Faculty, Department of Internal Medicine, Adana, Turkey

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Volkan Izol Urology Department, Cukurova University Medical Faculty, Adana, Turkey

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Şeyda Erdoğan Pathology Department, Cukurova University Medical Faculty, Adana, Turkey

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Yıldırım Bayazıt Urology Department, Cukurova University Medical Faculty, Adana, Turkey

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Murat Sert Division of Endocrinology, Internal Medicine and Endocrinology, Cukurova University Medical Faculty, Department of Internal Medicine, Adana, Turkey

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Tamer Tetiker Division of Endocrinology, Internal Medicine and Endocrinology, Cukurova University Medical Faculty, Department of Internal Medicine, Adana, Turkey

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hyperaldosteronism, hypercortisolism and pheochromocytoma. Plasma renin/aldosterone ratios, plasma normetanephrine, metanephrines and urinary free cortisol (UFC) were also studied. Autonomous cortisol secretion was described as serum cortisol >1.8 µg/dL following 1

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Fidéline Bonnet-Serrano Université Paris Cité, Paris, France
Inserm U1016-CNRS UMR8104, Paris, France
Hormonology Department, Cochin Hospital, Paris, France

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Maxime Barat Université Paris Cité, Paris, France
Inserm U1016-CNRS UMR8104, Paris, France
Radiology Department, Cochin Hospital, Paris, France

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Anna Vaczlavik Université Paris Cité, Paris, France
Inserm U1016-CNRS UMR8104, Paris, France
Reference Center for Rare Adrenal Diseases, Endocrinology Department, Cochin Hospital, Paris, France

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Anne Jouinot Inserm U1016-CNRS UMR8104, Paris, France

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Lucas Bouys Université Paris Cité, Paris, France
Inserm U1016-CNRS UMR8104, Paris, France
Reference Center for Rare Adrenal Diseases, Endocrinology Department, Cochin Hospital, Paris, France

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Christelle Laguillier-Morizot Université Paris Cité, Paris, France
Hormonology Department, Cochin Hospital, Paris, France
INSERM, Physiopathologie et Pharmacotoxicologie Placentaire Humaine : Microbiote Pré & Post natal, Paris, France

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Corinne Zientek Hormonology Department, Cochin Hospital, Paris, France

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Catherine Simonneau Hormonology Department, Cochin Hospital, Paris, France

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Etienne Larger Université Paris Cité, Paris, France
Inserm U1016-CNRS UMR8104, Paris, France
Diabetology Department, Cochin Hospital, Paris, France

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Laurence Guignat Reference Center for Rare Adrenal Diseases, Endocrinology Department, Cochin Hospital, Paris, France

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Lionel Groussin Université Paris Cité, Paris, France
Inserm U1016-CNRS UMR8104, Paris, France
Reference Center for Rare Adrenal Diseases, Endocrinology Department, Cochin Hospital, Paris, France

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Guillaume Assié Université Paris Cité, Paris, France
Inserm U1016-CNRS UMR8104, Paris, France
Reference Center for Rare Adrenal Diseases, Endocrinology Department, Cochin Hospital, Paris, France

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Jean Guibourdenche Université Paris Cité, Paris, France
Hormonology Department, Cochin Hospital, Paris, France
INSERM, Physiopathologie et Pharmacotoxicologie Placentaire Humaine : Microbiote Pré & Post natal, Paris, France

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Ioannis Nicolis Université Paris Cité, Paris, France
UR 7537 BioSTM, Paris, France

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Marie-Claude Menet Institut de Chimie Physique, Université Paris-Saclay-CNRS, UMR8000, Orsay, France

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Jérôme Bertherat Université Paris Cité, Paris, France
Inserm U1016-CNRS UMR8104, Paris, France
Reference Center for Rare Adrenal Diseases, Endocrinology Department, Cochin Hospital, Paris, France

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series) but they can be responsible for autonomous cortisol secretion in about 12% of cases (1–29% among series) and for aldosterone secretion in 2.5% of cases (1.6–3.3% among series) ( 5 ). Primary bilateral macronodular adrenal hyperplasia (PBMAH) is

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