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Weixi Wang Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-Institute for Endocrinology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China

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Rulai Han Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-Institute for Endocrinology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China

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Lei Ye Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-Institute for Endocrinology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China

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Jing Xie Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China

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Bei Tao Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-Institute for Endocrinology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China

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Fukang Sun Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China

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Ran Zhuo Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China

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Xi Chen Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China

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Xiaxing Deng Pancreatic Disease Centre, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China

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Cong Ye Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China

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Hongyan Zhao Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-Institute for Endocrinology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China

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Shu Wang Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases and Shanghai E-Institute for Endocrinology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China

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found no sign of Cushing’s syndrome. Evaluation of adrenal hormone revealed loss of cortisol rhythm (8:00–16:00–24:00 25.81–25.77–23.82 μg/dL) and elevated urinary free cortisol (UFC) (1287 μg/24 h, normal 21–111 μg/24 h). Overnight dexamethasone

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Sonja Kunz Department of Medicine IV, University Hospital, Ludwig Maximilian University Munich, Munich, Germany

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Xiao Wang Department of Medicine IV, University Hospital, Ludwig Maximilian University Munich, Munich, Germany

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Uta Ferrari Department of Medicine IV, University Hospital, Ludwig Maximilian University Munich, Munich, Germany

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Michael Drey Department of Medicine IV, University Hospital, Ludwig Maximilian University Munich, Munich, Germany

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Marily Theodoropoulou Department of Medicine IV, University Hospital, Ludwig Maximilian University Munich, Munich, Germany

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Katharina Schilbach Department of Medicine IV, University Hospital, Ludwig Maximilian University Munich, Munich, Germany

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Martin Reincke Department of Medicine IV, University Hospital, Ludwig Maximilian University Munich, Munich, Germany

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Margit Heier Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
KORA Study Centre, University Hospital of Augsburg, Augsburg, Augsburg, Germany

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Annette Peters Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
German Centre for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Munich, Germany

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Wolfgang Koenig German Centre for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Munich, Germany
German Heart Centre Munich, Technical University of Munich, Munich, Germany
Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany

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Tanja Zeller Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany
German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany

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Barbara Thorand Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

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Martin Bidlingmaier Department of Medicine IV, University Hospital, Ludwig Maximilian University Munich, Munich, Germany

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transitions. According to the manufacturer, all calibrators and QCs are traceable to certified reference materials, or, if not available for certain steroid, to primary standards. For cortisol, progesterone and testosterone NIST 971 reference material is used

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Elena Valassi Endocrinology Department, Germans Trias i Pujol Hospital and Research Institute, Badalona, Barcelona, Spain
IRCCS, Istituto Auxologico Italiano, Milan, Italy
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Iacopo Chiodini IRCCS, Istituto Auxologico Italiano, Milan, Italy
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Richard A Feelders Division of Endocrinology, Erasmus Medical Centre, Rotterdam, Netherlands

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Cornelie D Andela Division of Endocrinology and Centre for Endocrine Tumours, Leiden University Medical Centre, Leiden, Netherlands

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Margueritta Abou-Hanna HRA Pharma Rare Diseases, Châtillon, France

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Sarah Idres HRA Pharma Rare Diseases, Châtillon, France

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Antoine Tabarin Department of Endocrinology and INSERM U862 University and CHU of Bordeaux, Pessac, France

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Introduction Cushing’s syndrome (CS) is a morbid endocrine condition due to prolonged exposure to high circulating cortisol levels ( 1 , 2 , 3 ). Hypercortisolism may cause irreversible physical and psychological changes in several tissues

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Sebastião Freitas de Medeiros Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil
Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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Cinthia Marenza Ormond Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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Matheus Antônio Souto de Medeiros Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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Nayara de Souza Santos Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil
Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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Camila Regis Banhara Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil
Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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Márcia Marly Winck Yamamoto Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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, cortisol (F), and insulin were measured using a chemiluminescence assay with a sensitivity of 1.0 nmol/L, 0.08 µmol/L, 0.19 nmol/L, and 2 µIU/mL, respectively (Siemens Medical Solution Diagnostics, CA, USA). The intra- and inter-assay coefficients of

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Jung Soo Lim Department of Internal Medicine, Institute of Evidence-Based Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do, South Korea

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Seung-Eun Lee Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, South Korea

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Jung Hee Kim Department of Internal Medicine, Seoul National University College of Medicine, Jongno-gu, Seoul, South Korea

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Jae Hyeon Kim Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, South Korea

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The Korean Adrenal Gland and Endocrine Hypertension Study Group, Korean Endocrine Society
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factors include advanced tumor stage, cortisol excess, and older age ( 18 ). In addition, poor prognosis is associated with pathologic factors, including tumor grade, mitotic count, Ki-67 proliferation index ( 21 ), resection status ( 22 ), and results of

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Lára Ósk Eggertsdóttir Claessen Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland
Department of Emergency Medicine, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland

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Hafrún Kristjánsdóttir Physical Activity, Physical Education, Sport, and Health (PAPESH) Research Centre, Sports Science Department, School of Social Sciences, Reykjavik University, Reykjavik, Iceland

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María Kristín Jónsdóttir Mental Health Services, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland
Department of Psychology, School of Social Sciences, Reykjavik University, Reykjavik, Iceland

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Sigrún Helga Lund deCODE Genetics, Inc/Amgen Inc., Reykjavik, Iceland
School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland

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Ingunn Unnsteinsdóttir Kristensen Department of Psychology, School of Social Sciences, Reykjavik University, Reykjavik, Iceland

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Helga Ágústa Sigurjónsdóttir Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland
Department of Medicine, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland

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RV. ACTH, adrenocorticotropic hormone; anti-TPO, anti-thyroid peroxidase antibodies; GHRH–arginine, growth hormone-releasing hormone and arginine; ITT, insulin tolerance test; MRI, magnetic resonance imaging; S-cortisol, serum cortisol; S-IGF1, serum

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Tatiana V Novoselova Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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Peter J King Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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Leonardo Guasti Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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Louise A Metherell Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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Adrian J L Clark Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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Li F Chan Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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have a negative feedback on the release of CRH and AVP at the hypothalamus and ACTH at the pituitary, thus providing tight regulation of cortisol production. ACTH receptor/melanocortin-2-receptor The ACTH receptor (also known as the melanocortin

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Anastasia P Athanasoulia-Kaspar Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany

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Matthias K Auer Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany

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Günter K Stalla Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany

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Mira Jakovcevski Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany

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hypercortisolism ( 36 ). Furthermore, TL has been evaluated in other conditions with increased endogenous cortisol such as chronic stress exposure and post-traumatic stress disorder ( 37 ). Shorter TL has been reported for both neuropsychiatric conditions

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Kathrin R Frey Department of Medicine I, Endocrine and Diabetes Unit, University Hospital, University of Würzburg, Würzburg, Germany

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Tina Kienitz Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

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Julia Schulz Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

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Manfred Ventz Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

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Kathrin Zopf Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

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Marcus Quinkler Endocrinology in Charlottenburg, Berlin, Germany

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of GCs in PAI and CAH still tends to be more than the total daily endogenous cortisol secretion seen in healthy subjects (5–10 mg of cortisol/m 2 of body surface area/day) ( 1 ) possibly triggering long-term morbidities such as osteoporosis. GC

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Carla Scaroni Dipartimento di Medicina, U.O.C. Endocrinologia, Università di Padova, Padova, Italy

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Nora M Albiger Dipartimento di Medicina, U.O.C. Endocrinologia, Università di Padova, Padova, Italy

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Serena Palmieri Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy

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Davide Iacuaniello Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Napoli, Italy

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Chiara Graziadio Department of Experimental Medicine, University La Sapienza, Rome, Italy

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Luca Damiani Department of Medical Sciences, Endocrinology and Internal Medicine Section, University of Ferrara, Ferrara, Italy

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Marialuisa Zilio Dipartimento di Medicina, U.O.C. Endocrinologia, Università di Padova, Padova, Italy

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

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Annamaria Colao Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Napoli, Italy

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Rosario Pivonello Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Napoli, Italy

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the Altogether to Beat Cushing’s Syndrome (ABC) study group
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cortisol at 08:00 h (29 µg/dL; n.v. 5–25), and high urinary free cortisol (UFC) (280 µg/24 h; n.v. 36–137), while ACTH levels at 08:00 h were in the normal range (26 pg/mL; n.v. 10–50). The patient’s diabetes was poorly controlled (HbA1c 8%). The

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