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Emre Murat Altinkilic Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Department of BioMedical Research, University of Bern, Bern, Switzerland

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Philipp Augsburger Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Department of BioMedical Research, University of Bern, Bern, Switzerland
Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland

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Amit V Pandey Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Department of BioMedical Research, University of Bern, Bern, Switzerland

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Christa E Flück Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Department of BioMedical Research, University of Bern, Bern, Switzerland

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-classic form of LCAH caused by less severe STAR variants has been identified variably in larger cohorts of individuals studied for primary adrenal insufficiency in Japan (30%) and Turkey (11%), respectively ( Guran et al. 2016 , Amano et al. 2017 ). In

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C Suárez Instituto de Biología y Medicina Experimental, CONICET, V, Obligado 2490, Buenos Aires 1428, Argentina

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J Vela Instituto de Biología y Medicina Experimental, CONICET, V, Obligado 2490, Buenos Aires 1428, Argentina

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I García-Tornadú Instituto de Biología y Medicina Experimental, CONICET, V, Obligado 2490, Buenos Aires 1428, Argentina

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D Becu-Villalobos Instituto de Biología y Medicina Experimental, CONICET, V, Obligado 2490, Buenos Aires 1428, Argentina

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al. 2002 ), in pubertal development, and in aging ( Shealy 1995 , Kroboth et al. 1999 ). DHEA replacement in old healthy people as well as in patients with primary adrenal insufficiency produced an increase in serum IGF-I ( Arlt et al. 1999

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Jin Yu Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, China

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Yuhuan Liu Department of Gynecology and Obstetrics, Changhai Hospital, Naval Medical University, Shanghai, China

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Danying Zhang Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, China

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Dongxia Zhai Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, China

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Linyi Song Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, China

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Zailong Cai Department of Biochemistry and Molecular Biology, Naval Medical University, Shanghai, China

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Chaoqin Yu Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, China

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hyperplasia, which manifests as a primary adrenal insufficiency and a sexual development disorder ( Welzel et al. 2008 ). Inversely, overexpression of HSD3B2 in ovarian tissues or the adrenal cortex leads to excessive androgen synthesis, which manifests as

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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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://doi.org/10.1126/science.289.5488.2344 ) Bancos I Hazeldine J Chortis V Hampson P Taylor AE Lord JM Arlt W 2017 Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality

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Rick van der Geest Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Gorlaeus Laboratories, Leiden, The Netherlands

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Ronald J van der Sluis Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Gorlaeus Laboratories, Leiden, The Netherlands

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Albert K Groen Departments of Pediatrics and Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands

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Miranda Van Eck Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Gorlaeus Laboratories, Leiden, The Netherlands

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Menno Hoekstra Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Gorlaeus Laboratories, Leiden, The Netherlands

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2018 An overview of inborn errors of metabolism manifesting with primary adrenal insufficiency . Reviews in Endocrine and Metabolic Disorders 19 53 – 67 . ( https://doi.org/10.1007/s11154-018-9447-2 ) 10.1007/s11154-018-9447-2 Hartman HB

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R Prasad Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK

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J C Kowalczyk Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK

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E Meimaridou Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK

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H L Storr Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK

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L A Metherell Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Centre for Endocrinology, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK

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therapeutic intervention. Antioxidant defence within the adrenal certainly warrants further investigation and other components within this pathway may prove to be causative in the aetiology of as yet unaccounted for cases of primary adrenal insufficiency

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C Crescioli
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L Cosmi
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E Borgogni
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V Santarlasci
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S Gelmini
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M Sottili
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E Sarchielli
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B Mazzinghi
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M Francalanci
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A Pezzatini
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G Perigli
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G B Vannelli
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F Annunziato
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M Serio
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ligand-10 in autoimmune primary adrenal insufficiency and in vitro expression in human adrenal cells primary cultures after stimulation with proin-flammatory cytokines. Journal of Clinical Endocrinology and Metabolism 90 2357 –2367

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Ernane Torres Uchoa Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil
Department of Physiological Sciences, State University of Londrina, Londrina, Brazil

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Paula Beatriz Marangon Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil

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Rodrigo Rorato Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil
Biotechnology Unit, University of Ribeirao Preto, Ribeirao Preto, Brazil

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Silvia Graciela Ruginsk Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil
Department of Physiological Sciences, Biomedical Sciences Institute, Federal University of Alfenas, Alfenas, Brazil

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Lucas Kniess Debarba Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil

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Jose Antunes-Rodrigues Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil

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Lucila L K Elias Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil

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primary adrenal insufficiency in humans ( Freedman et al. 1985 , Oelkers 1996 , Uchoa et al. 2009 a , b ). The hypophagic effect induced by ADX is associated with changes in the expression of hypothalamic neuropeptides involved in the

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Louise Grahnemo Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Caroline Jochems Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden
Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Annica Andersson Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Cecilia Engdahl Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden
Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Claes Ohlsson Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Ulrika Islander Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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Hans Carlsten Departments of Rheumatology and Inflammation Research, Internal Medicine and Clinical Nutrition, Laboratory of Tumor Immunology and Biology, Centre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, Sweden

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( Svensson et al . 2005 ). In addition, the degree of bone loss was similar to that in controls. Patients treated with low doses of glucocorticoids for insufficient levels of endogenous glucocorticoids, caused by primary adrenal insufficiency or congenital

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