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Paul-Martin Holterhus Department of Pediatrics I, Pediatric Endocrinology and Diabetology, University Hospital of Schleswig-Holstein, UKSH, Campus Kiel and Christian Albrechts University, CAU, Kiel, Germany

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Alexandra Kulle Department of Pediatrics I, Pediatric Endocrinology and Diabetology, University Hospital of Schleswig-Holstein, UKSH, Campus Kiel and Christian Albrechts University, CAU, Kiel, Germany

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Anne-Marie Till Department of Pediatrics, Pediatric Hematology and Oncology, University Hospital of Schleswig-Holstein, UKSH, Campus Lübeck, Germany

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Caroline Stille Department of Pediatrics, Pediatric Hematology and Oncology, University Hospital of Schleswig-Holstein, UKSH, Campus Lübeck, Germany

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Tabea Lamprecht Department of Pediatrics I, Pediatric Endocrinology and Diabetology, University Hospital of Schleswig-Holstein, UKSH, Campus Kiel and Christian Albrechts University, CAU, Kiel, Germany

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Simon Vieth Department of Pediatrics I, Pediatric Hematology and Oncology, University Hospital of Schleswig-Holstein, UKSH, Campus Kiel and Christian-Albrechts-University, CAU, Kiel, Germany

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Melchior Lauten Department of Pediatrics, Pediatric Hematology and Oncology, University Hospital of Schleswig-Holstein, UKSH, Campus Lübeck, Germany

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, have therefore been recommended ( 3 , 4 , 7 , 8 ). Prednisolone and dexamethasone are highly potent glucocorticoids with only a little mineralocorticoid effect. Consequently, the regulation of glucocorticoids has been the main focus to investigate

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Riccardo Pofi Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism and NIHR Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, UK

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Ilaria Bonaventura Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, Rome, Italy

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Joanne Duffy Department of Clinical Chemistry and Immunology, Heartlands Hospital, Birmingham, UK

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Zoe Maunsell Department of Clinical Biochemistry, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

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Brian Shine Department of Clinical Biochemistry, Oxford University Hospitals NHS Foundation Trust, Oxford, UK

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

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Jeremy W Tomlinson Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism and NIHR Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, UK

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Introduction Primary adrenal insufficiency (PAI) is a rare disease consisting of the inability of the adrenal cortex to produce adequate levels of glucocorticoids (GCs), with or without concomitant inadequate production of mineralocorticoids

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Thomas Reinehr Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Datteln, Germany

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Alexandra Kulle Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University Hospital of Schleswig – Holstein, UKSH, Campus Kiel/Christian Albrechts University of Kiel, CAU, Kiel, Germany

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Juliane Rothermel Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Datteln, Germany

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Caroline Knop-Schmenn Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Datteln, Germany

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Nina Lass Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Datteln, Germany

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Christina Bosse Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Datteln, Germany

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Paul-Martin Holterhus Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University Hospital of Schleswig – Holstein, UKSH, Campus Kiel/Christian Albrechts University of Kiel, CAU, Kiel, Germany

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regulation of precursors of androgens and other steroid hormones within the steroid metabolome encompassing glucocorticoids, mineralocorticoids and estrogens is largely unknown in PCOS. Although PCOS has frequently been reported in adolescents, the

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Sophie Howarth Clinical and Translational Research Institute, Newcastle University, Newcastle upon Tyne, UK
Department of Endocrinology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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Luca Giovanelli Department of Endocrinology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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Catherine Napier Department of Endocrinology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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Simon H Pearce Clinical and Translational Research Institute, Newcastle University, Newcastle upon Tyne, UK
Department of Endocrinology, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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insufficient to meet the body’s needs. Overt mineralocorticoid deficiency causes the characteristic presentation of salt craving, postural hypotension, hyponatraemia and hyperkalaemia. Glucocorticoid deficiency causes loss of appetite, early satiety, weight

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Anne-Sophie C A M Koning Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Philippe C Habets Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Marit Bogaards Division of Endocrinology, Department of Medicine, 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 Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Hanneke M van Santen Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
Department of Pediatric Neuro-Oncology, Prinses Máxima Centrum, Utrecht, The Netherlands

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Judith M de Bont Department of Pediatric Neuro-Oncology, Prinses Máxima Centrum, Utrecht, The Netherlands

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Onno C Meijer Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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naturally produced glucocorticoid hormone cortisol. Cortisol also acts via the mineralocorticoid receptor (MR) in many tissues including the brain ( 6 ), but synthetic glucocorticoids have a clear preference for GR over MR ( 7 ). Both receptor types are

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Jorge Gabriel Ruiz-Sánchez Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Hospital Universitario Fundación Jiménez Díaz, Madrid, España
Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España

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Alfonso Luis Calle-Pascual Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, España

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Miguel Ángel Rubio-Herrera Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España

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María Paz De Miguel Novoa Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España

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Emilia Gómez-Hoyos Servicio de Endocrinología y Nutrición, Hospital Clínico Universitario de Valladolid, Valladolid, España

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Isabelle Runkle Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España

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Introduction Aldosterone and cortisol are the two main mineralocorticoids in humans. Under physiological conditions, aldosterone is the chief stimulatory ligand of the mineralocorticoid receptor (MR) in the principal cells of the distal

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Timothy J Morris Directorate of Biochemistry, Manchester University NHS Foundation Trust, Manchester, UK
Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK

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Andrew Whatmore Division of Developmental Biology and Medicine, University of Manchester, Royal Manchester Children’s Hospital, Manchester, UK

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Laura Hamilton Pathology Department, Clinical Biochemistry, Huddersfield Royal Infirmary, Lindley, Huddersfield, UK

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Beverly Hird Directorate of Biochemistry, Manchester University NHS Foundation Trust, Manchester, UK

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Eric S Kilpatrick Directorate of Biochemistry, Manchester University NHS Foundation Trust, Manchester, UK

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Lesley Tetlow Directorate of Biochemistry, Manchester University NHS Foundation Trust, Manchester, UK

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Peter Clayton Division of Developmental Biology and Medicine, University of Manchester, Royal Manchester Children’s Hospital, Manchester, UK

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Introduction Patients with adrenal insufficiency are treated with glucocorticoid and mineralocorticoid replacement ( 1 , 2 ). Plasma renin measured as either plasma renin activity (PRA) or plasma renin concentration (PRC) is used to evaluate

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Aneta Gawlik Department of Pediatrics and Pediatric Endocrinology, School of Medicine in Katowice, Medical University of Silesia, Upper Silesia Children’s Care Health Centre, Katowice, Poland

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Michael Shmoish Bioinformatics Knowledge Unit, Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion – Israel Institute of Technology, Haifa, Israel

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Michaela F Hartmann Steroid Research & Mass Spectrometry Unit, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany

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Stefan A Wudy Steroid Research & Mass Spectrometry Unit, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany

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Zbigniew Olczak Department of Diagnostic Imaging, Upper Silesia Children’s Care Health Centre, Katowice, Poland

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Katarzyna Gruszczynska Department of Diagnostic Imaging, School of Medicine in Katowice, Medical University of Silesia, Upper Silesia Children’s Care Health Centre, Katowice, Poland

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Ze’ev Hochberg Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

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-transformed concentrations of steroid metabolites (androgens, glucocorticoids and mineralocorticoids) in liver diseases (L1) and with non-liver disease features (L0) patients. Table 3 Ratio of steroid metabolites (enzyme activity): differences between patients

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Lukas Engler Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Christian Adolf Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Daniel A Heinrich Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Anna-Katharine Brem Max-Planck-Institute of Psychiatry, Munich, Germany
Division of Interventional Cognitive Neurology, Department of Neurology, Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

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Anna Riester Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Anna Franke Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Felix Beuschlein Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Martin Reincke Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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Axel Steiger Max-Planck-Institute of Psychiatry, Munich, Germany

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Heike Künzel Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU München, Munchen, Germany

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affected than males ( 1 ). These patients were also found to have a lower quality of life (QoL) even after treatment with either a mineralocorticoid receptor (MR) antagonist or adrenalectomy (ADX) ( 2 ). Cognitive deficits are prevalent in depression ( 3

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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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conversion), and consecutive along the three different pathways (glucocorticoids, androgens and mineralocorticoids), was determined using LC-MS/MS. They are shown in blue in Fig. 1 . Figure 1 Adrenal steroidogenesis diagram. Steroidogenic enzymes are

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