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Eva M G Viho Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands

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Jan Kroon Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
Corcept Therapeutics, Menlo Park, CA, USA

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Richard A Feelders Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, the Netherlands

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René Houtman Precision Medicine Lab, Oss, the Netherlands

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Elisabeth S R van den Dungen Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, the Netherlands

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Alberto M Pereira Department of Endocrinology and Metabolism, Amsterdam University Medical Center, Amsterdam, the Netherlands

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Hazel J Hunt Corcept Therapeutics, Menlo Park, CA, USA

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Leo J Hofland Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, the Netherlands

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Onno C Meijer Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
Corcept Therapeutics, Menlo Park, CA, USA

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gland ( Spencer & Deak 2017 ). Dysregulation of GC secretion is responsible for several pathologies, the most obvious being Cushing’s syndrome (CS). Endogenous CS is a condition characterized by cortisol overproduction that can be ACTH-dependent, caused

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Guillermo García-Eguren Group of Endocrine Disorders, IDIBAPS, Barcelona, Spain

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Oriol Giró Group of Endocrine Disorders, IDIBAPS, Barcelona, Spain

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María del Mar Romero Department of Biochemistry and Molecular Biomedicine, Section of Nutrition, Faculty of Biology, University of Barcelona, Barcelona, Spain
Institute of Biomedicine, University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Obesidad y Nutrición (CIBEROBN), Carlos III Health Institute, Madrid, Spain

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Mar Grasa Department of Biochemistry and Molecular Biomedicine, Section of Nutrition, Faculty of Biology, University of Barcelona, Barcelona, Spain
Institute of Biomedicine, University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Obesidad y Nutrición (CIBEROBN), Carlos III Health Institute, Madrid, Spain

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Felicia A Hanzu Group of Endocrine Disorders, IDIBAPS, Barcelona, Spain
Department of Endocrinology and Nutrition, Hospital Clinic of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Carlos III Health Institute, Madrid, Spain
Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain

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Introduction Chronic exposure to excess glucocorticoid (GC) levels, resulting from either endogenous Cushing’s syndrome (CS) or exogenous GC therapy, causes several adverse outcomes, including obesity, insulin resistance, dyslipidemia

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Stuart A Morgan Institute of Metabolism and Systems Research, Institute of Biomedical Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, UK

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Zaki K Hassan-Smith Institute of Metabolism and Systems Research, Institute of Biomedical Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, UK

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Craig L Doig Institute of Metabolism and Systems Research, Institute of Biomedical Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, UK

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Mark Sherlock Institute of Metabolism and Systems Research, Institute of Biomedical Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, UK

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Paul M Stewart Institute of Metabolism and Systems Research, Institute of Biomedical Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, UK
School of Medicine, Worsley Building, University of Leeds, Leeds, UK

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Gareth G Lavery Institute of Metabolism and Systems Research, Institute of Biomedical Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, UK

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Introduction The pathophysiological effects of glucocorticoids (GCs) are well described and impact upon almost all organ systems within the body. This is highlighted in patients with GC excess, Cushing’s syndrome, characterized by central

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Stuart A Morgan Institute of Metabolism & Systems Research, University of Birmingham, Birmingham, UK
Department of Biosciences, Nottingham Trent University, Nottingham, UK

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Laura L Gathercole Department of Biological & Medical Sciences, Oxford Brooks University, Oxford, UK

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Zaki K Hassan-Smith Institute of Metabolism & Systems Research, University of Birmingham, Birmingham, UK

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Jeremy Tomlinson Radcliffe Department of Medicine, University of Oxford, Oxford, UK

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Paul M Stewart Institute of Metabolism & Systems Research, University of Birmingham, Birmingham, UK
NEXUS, Discovery Way, University of Leeds, Leeds, UK

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Gareth G Lavery Institute of Metabolism & Systems Research, University of Birmingham, Birmingham, UK
Department of Biosciences, Nottingham Trent University, Nottingham, UK

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improve healthspan. Interestingly, the aged phenotype shares several metabolic similarities with that of circulatory glucocorticoid (GC) excess (Cushing’s syndrome), including insulin resistance, type 2 diabetes mellitus, central obesity, hypertension

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Samuel R Heaselgrave Center of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Centre for Systems Health and Integrated Metabolic Research, Department of Biosciences, Nottingham Trent University, Birmingham, UK
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

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Silke Heising Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

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Stuart A Morgan Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

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David M Carthwright Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

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Michael Sagmeister Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

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Rowan S Hardy Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

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Craig L Doig Centre for Systems Health and Integrated Metabolic Research, Department of Biosciences, Nottingham Trent University, Birmingham, UK

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Nicholas Morton Centre for Systems Health and Integrated Metabolic Research, Department of Biosciences, Nottingham Trent University, Birmingham, UK
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK

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Kostas Tsintzas MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, UK

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Gareth G Lavery Centre for Systems Health and Integrated Metabolic Research, Department of Biosciences, Nottingham Trent University, Birmingham, UK

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dysfunction, most notably Cushing’s syndrome, which is characterised by a well-documented phenotype in humans and rodents ( Lacroix et al. 2015 , Lonser et al. 2017 ). This phenotype, which can be readily induced in mice for experimental purposes

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Marianna Minnetti Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Valeria Hasenmajer Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Riccardo Pofi Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Mary Anna Venneri Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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Krystallenia I Alexandraki Endocrine Unit, 1st Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece

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Andrea M Isidori Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

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first sign of CVD in Cushing’s syndrome ( Isidori et al. 2015 a ), and patients with mild autonomous cortisol secretion exhibit increased arterial stiffness and cardiac remodeling ( Sbardella et al. 2018 ). Even though an exhaustive discussion of

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Ping Ye
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Barbara Mariniello
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Franco Mantero
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Hirotaka Shibata
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William E Rainey
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. There are compelling evidence to support elevated expression of certain G-protein-coupled receptors (GPCRs) as a cause of some cases of adrenocorticotrophin (ACTH)-independent Cushing’s syndrome ( Bugalho et al. 2000 , Dall’Asta et al. 2004

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Getu Abraham Institute of Pharmacology, Pharmacy and Toxicology, University of Leipzig, An den Tierkliniken 15, D-04103 Leipzig, Germany

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Fioralba Demiraj Institute of Pharmacology, Pharmacy and Toxicology, University of Leipzig, An den Tierkliniken 15, D-04103 Leipzig, Germany

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Fritz Rupert Ungemach Institute of Pharmacology, Pharmacy and Toxicology, University of Leipzig, An den Tierkliniken 15, D-04103 Leipzig, Germany

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administration and the risk to induce long-term adverse effects. Recently, a case of acute iatrogenic Cushing’s syndrome and HPA axis suppression which persisted 8 months has been reported in humans after a single-dose i.m. depot TAA administration ( Iglesias et

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M K Akhtar Institute of Biological Sciences, Cledwyn Building, University of Wales, Aberystwyth, Ceredigion SY23 3DD, UK

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S L Kelly Institute of Biological Sciences, Cledwyn Building, University of Wales, Aberystwyth, Ceredigion SY23 3DD, UK

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M A Kaderbhai Institute of Biological Sciences, Cledwyn Building, University of Wales, Aberystwyth, Ceredigion SY23 3DD, UK

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consequently produces mineralocorticoids. CYP17 dysfunction has been associated with a number of diseases including polycystic ovary syndrome ( Qin & Rosenfield 1998 , Miller 2002 , Strauss 2003 ), Cushing’s syndrome ( Ogo et al. 1991 ), congenital adrenal

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Federica Innocenti DAHFMO, Unit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy

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Lidia Cerquetti Endocrinology, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy

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Serena Pezzilli Endocrinology, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy

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Barbara Bucci S. Pietro Hospital Fatebenefratelli, Rome, Italy

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Vincenzo Toscano Endocrinology, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy

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Rita Canipari DAHFMO, Unit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy

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

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clinical presentation of ACC is frequently characterized by overt Cushing’s syndrome ( Fassnacht et al. 2011 , Else et al. 2014 ). Fertility and the resulting pregnancy rarely occur in Cushing’s syndrome because this condition includes symptoms of

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