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Emanuelle Nunes-Souza Pelé Pequeno Príncipe Research Institute, Água Verde, Curitiba, Parana, Brazil
Faculdades Pequeno Príncipe, Rebouças, Curitiba, Parana, Brazil
Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC) at Universidade Federal do Paraná, Agostinho Leão Jr., Glória, Curitiba, Parana, Brazil

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Mônica Evelise Silveira Laboratório Central de Análises Clínicas, Hospital de Clínicas, Universidade Federal do Paraná, Centro, Curitiba, Paraná, Brazil

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Monalisa Castilho Mendes Pelé Pequeno Príncipe Research Institute, Água Verde, Curitiba, Parana, Brazil
Faculdades Pequeno Príncipe, Rebouças, Curitiba, Parana, Brazil
Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC) at Universidade Federal do Paraná, Agostinho Leão Jr., Glória, Curitiba, Parana, Brazil

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Seigo Nagashima Serviço de Anatomia Patológica, Hospital de Clínicas, Universidade Federal do Paraná, General Carneiro, Alto da Glória, Curitiba, Parana, Brazil
Departamento de Medicina, PUC-PR, Prado Velho, Curitiba, Parana, Brazil

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Caroline Busatta Vaz de Paula Serviço de Anatomia Patológica, Hospital de Clínicas, Universidade Federal do Paraná, General Carneiro, Alto da Glória, Curitiba, Parana, Brazil
Departamento de Medicina, PUC-PR, Prado Velho, Curitiba, Parana, Brazil

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Guilherme Guilherme Vieira Cavalcante da Silva Serviço de Anatomia Patológica, Hospital de Clínicas, Universidade Federal do Paraná, General Carneiro, Alto da Glória, Curitiba, Parana, Brazil
Departamento de Medicina, PUC-PR, Prado Velho, Curitiba, Parana, Brazil

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Giovanna Silva Barbosa Serviço de Anatomia Patológica, Hospital de Clínicas, Universidade Federal do Paraná, General Carneiro, Alto da Glória, Curitiba, Parana, Brazil
Departamento de Medicina, PUC-PR, Prado Velho, Curitiba, Parana, Brazil

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Julia Belgrowicz Martins Pelé Pequeno Príncipe Research Institute, Água Verde, Curitiba, Parana, Brazil
Faculdades Pequeno Príncipe, Rebouças, Curitiba, Parana, Brazil

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Lúcia de Noronha Serviço de Anatomia Patológica, Hospital de Clínicas, Universidade Federal do Paraná, General Carneiro, Alto da Glória, Curitiba, Parana, Brazil
Departamento de Medicina, PUC-PR, Prado Velho, Curitiba, Parana, Brazil

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Luana Lenzi Departamento de Análises Clínicas, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

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José Renato Sales Barbosa Pelé Pequeno Príncipe Research Institute, Água Verde, Curitiba, Parana, Brazil
Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC) at Universidade Federal do Paraná, Agostinho Leão Jr., Glória, Curitiba, Parana, Brazil

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Rayssa Danilow Fachin Donin Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC) at Universidade Federal do Paraná, Agostinho Leão Jr., Glória, Curitiba, Parana, Brazil

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Juliana Ferreira de Moura Pós Graduação em Microbiologia, Parasitologia e Patologia, Departamento de Patologia Básica – UFPR, Curitiba, Brazil

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Gislaine Custódio Faculdades Pequeno Príncipe, Rebouças, Curitiba, Parana, Brazil
Laboratório Central de Análises Clínicas, Hospital de Clínicas, Universidade Federal do Paraná, Centro, Curitiba, Paraná, Brazil

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Cleber Machado-Souza Pelé Pequeno Príncipe Research Institute, Água Verde, Curitiba, Parana, Brazil
Faculdades Pequeno Príncipe, Rebouças, Curitiba, Parana, Brazil
Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC) at Universidade Federal do Paraná, Agostinho Leão Jr., Glória, Curitiba, Parana, Brazil

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Enzo Lalli Institut de Pharmacologie Moléculaire et Cellulaire CNRS, Sophia Antipolis, Valbonne, France

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Bonald Cavalcante de Figueiredo Pelé Pequeno Príncipe Research Institute, Água Verde, Curitiba, Parana, Brazil
Faculdades Pequeno Príncipe, Rebouças, Curitiba, Parana, Brazil
Centro de Genética Molecular e Pesquisa do Câncer em Crianças (CEGEMPAC) at Universidade Federal do Paraná, Agostinho Leão Jr., Glória, Curitiba, Parana, Brazil
Departamento de Saúde Coletiva, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

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Utriainen P Jääskeläinen J Romppanen J Voutilainen R Childhood metabolic syndrome and its components in premature adrenarche . Journal of Clinical Endocrinology and Metabolism 2007 92 4282 – 4285 . ( https://doi.org/10.1210/jc.2006-2412 ) 9

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Ekaterina Koledova Biopharma Global Medical Affairs, General Medicine and Endocrinology, Merck KGaA, Darmstadt, Germany

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George Stoyanov Biopharma Global Medical Affairs, General Medicine and Endocrinology, Merck KGaA, Darmstadt, Germany

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Leroy Ovbude Business & Decision Life Sciences, Brussels, Woluwe-Saint-Lambert, Belgium

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Peter S W Davies Children’s Nutrition Research Centre, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia

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.1159/000281323 6 Kappoor R Burke S Sparrow S Hughes I Dunger D Ong K Acerini C. Monitoring of concordance in growth hormone therapy . Archives of Disease in Childhood 2008 93 147 – 148 . ( https://doi.org/10.1136/adc.2006.114249 ) 10.1136/adc

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Olli Helminen Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University, Hospital and University of Oulu, Oulu, Finland
Surgery Research Unit, Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland

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Tytti Pokka Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University, Hospital and University of Oulu, Oulu, Finland

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Susanna Aspholm Tampere Centre for Child Health Research, Tampere University Hospital, Tampere, Finland

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Jorma Ilonen Immunogenetics Laboratory, University of Turku, Turku, Finland
Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland

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Olli G Simell Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland

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Mikael Knip Tampere Centre for Child Health Research, Tampere University Hospital, Tampere, Finland
Pediatric Research Center, New Children’s Hospital, Helsinki University Hospital, Helsinki, Finland
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland

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Riitta Veijola Department of Pediatrics, PEDEGO Research Group, Medical Research Center, Oulu University, Hospital and University of Oulu, Oulu, Finland

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Introduction Type 1 diabetes is one of the most common chronic diseases in childhood. The incidence rate has been rising throughout the Western world ( 1 ). The incidence is highest in Finland, in 2006 as high as 64.3 per 100,000 children

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Trine Holm Johannsen Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Jakob Albrethsen Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Vassos Neocleous The Cyprus Institute of Neurology and Genetics, Department of Molecular Genetics, Function and Therapy, Nicosia, Cyprus

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Federico Baronio S. Orsola-Malpighi University Hospital, Department of Medical and Surgical Sciences, Bologna, Italy

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Martine Cools Department of Pediatrics, Division of Pediatric Endocrinology, Ghent University Hospital and Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium

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Lise Aksglaede Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Niels Jørgensen Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Peter Christiansen Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Meropi Toumba The Cyprus Institute of Neurology and Genetics, Department of Molecular Genetics, Function and Therapy, Nicosia, Cyprus
Pediatric Endocrinology Clinic, Department of Pediatrics, Aretaeio Hospital, Nicosia, Cyprus

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Pavlos Fanis The Cyprus Institute of Neurology and Genetics, Department of Molecular Genetics, Function and Therapy, Nicosia, Cyprus

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Marie Lindhardt Ljubicic Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Denmark

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adrenal rest tumors (TARTs) which may be present already in childhood and adolescence ( 4 ). The presence of TART constitutes a diagnostic and management challenge. Usually, TARTs are bilaterally localized, benign tumors that have been assumed to derive

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Nobuo Matsuura Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Tadashi Kaname Department of Genome Medicine, National Research Institute for Child Health and Development, Tokyo, Japan

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Norio Niikawa Health Sciences University of Hokkaido, Sapporo, Japan

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Yoshihide Ooyama Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Osamu Shinohara Shinohara Child Clinic, Machida, Japan

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Yukifumi Yokota Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Shigeyuki Ohtsu Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Noriyuki Takubo Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Kazuteru Kitsuda Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Keiko Shibayama Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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Fumio Takada Department of Medical Genetics, Kitasato University Graduate School of Medical Science, Sagamihara, Japan

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Akemi Koike Miyanosawa Child Clinic, Sapporo, Japan

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Hitomi Sano Department of Pediatric, Sapporo City General Hospital, Sapporo, Japan

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Yoshiya Ito Department of Clinical Medicine, Japanese Red Cross Hospital Collage of Nursing, Kitami, Japan

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Kenji Ishikura Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan

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. Figure 1 Hand X-rays of patients A-1 in childhood and adulthood and B-1 in adulthood. Unlike in B-1, there is severe shortening of metacarpal and phalangeal bones and cone-shaped epiphyses in case A-1, in which a PDE4D pathogenic variant was

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Sebastian Franik Department of Obstetrics and Gynaecology, Radboudumc, Nijmegen, The Netherlands

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Kathrin Fleischer Department of Obstetrics and Gynaecology, Radboudumc, Nijmegen, The Netherlands

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Barbara Kortmann Department of Pediatric Urology, Radboudumc, Nijmegen, The Netherlands

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Nike M Stikkelbroeck Department of Internal Medicine, Radboudumc, Nijmegen, The Netherlands

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Kathleen D’Hauwers Department of Urology, Radboudumc, Nijmegen, The Netherlands

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Claire Bouvattier Department of Pediatric Endocrinology, Bicêtre Hospital, Paris Sud University, France

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Jolanta Slowikowska-Hilczer Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Poland

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Solange Grunenwald Department of Endocrinology and Metabolic Disease, Centre Hospitalier Universitaire de Toulouse, France

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Tim van de Grift Departments of Plastic Surgery and Medical Psychology, Amsterdam UMC location VUmc, Amsterdam, The Netherlands

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Audrey Cartault Department of Pediatrics, Hospital Des Enfants, Toulouse, France

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Annette Richter-Unruh Kinderendokrinologie und Diabetologie, Universitätsklinikum Ruhr-Universität Bochum, Kinderklinik, Bochum, Germany

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Nicole Reisch Department of Endocrinology, Medizinische Klinik and Poliklinik IV, University Hospital Munich, Munich, Germany

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Ute Thyen Klinik fur Kinder- und Jugendmedizin, Universitat zu Lubeck, Ratzeburger Allee, Lubeck, Germany

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Joanna IntHout Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands

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Hedi L Claahsen-van der Grinten Department of Pediatric Endocrinology, Amalia Childrens Hospital, Radboudumc, Nijmegen, The Netherlands

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the dsd-LIFE group
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the dsd-LIFE group

‘Are you on testosterone therapy at present? SC Yes No Age at diagnosis ‘At what age was your condition diagnosed?’ SC Before birth At birth (0–1 month) Infancy (1 month–3 years) Childhood (4

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Yi Wang Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, Beijing, China
National Center for Children’s Health, Beijing, China

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Yingying Xu Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Rongrong Xie Department of Endocrinology, Children’s Hospital of Soochow University, Suzhou, China

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Bingyan Cao Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, Beijing, China
National Center for Children’s Health, Beijing, China

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Yuan Ding Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, Beijing, China
National Center for Children’s Health, Beijing, China

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Jiayun Guo Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, Beijing, China
National Center for Children’s Health, Beijing, China

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Xiaoqiao Li Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, Beijing, China
National Center for Children’s Health, Beijing, China

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Xiaolin Ni Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, Beijing, China
National Center for Children’s Health, Beijing, China

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Zheng Yuan Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, Beijing, China
National Center for Children’s Health, Beijing, China

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Linqi Chen Department of Endocrinology, Children’s Hospital of Soochow University, Suzhou, China

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Liyang Liang Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

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Chunxiu Gong Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, Beijing, China
National Center for Children’s Health, Beijing, China

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-Mayer DE . Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood . Pediatrics 2007 120 e179 – e188 . ( https://doi.org/10.1542/peds.2006-3324 ) 3 Bougneres P Pantalone L Linglart A

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Maki Igarashi Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan

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Tadayuki Ayabe Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan

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Kiwako Yamamoto-Hanada Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Keiko Matsubara Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan

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Hatoko Sasaki Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Mayako Saito-Abe Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Miori Sato Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Nathan Mise Department of Environmental and Preventive Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan

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Akihiko Ikegami Department of Environmental and Preventive Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan

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Masayuki Shimono Regional Center for Pilot Study of Japan Environment and Children’s Study, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan

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Reiko Suga Regional Center for Pilot Study of Japan Environment and Children’s Study, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan

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Shouichi Ohga Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
Research Center for Environment and Developmental Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan

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Masafumi Sanefuji Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
Research Center for Environment and Developmental Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan

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Masako Oda Department of Public Health, Faculty of Life Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan

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Hiroshi Mitsubuchi Department of Neonatology, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan

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Takehiro Michikawa Japan Environment and Children’s Study Programme Office, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan

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Shin Yamazaki Japan Environment and Children’s Study Programme Office, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan

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Shoji Nakayama Japan Environment and Children’s Study Programme Office, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan

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Yukihiro Ohya Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Maki Fukami Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan

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. Further studies are necessary to clarify whether sex hormone production in childhood is associated with sexual maturation during puberty or reproductive function in adulthood. In conclusion, the results show that sexual dimorphism in sex hormone

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Jennifer K Y Ko Department of Women’s Health, University College London Hospital, London, UK

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Thomas F J King Department of Women’s Health, University College London Hospital, London, UK

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Louise Williams Department of Women’s Health, University College London Hospital, London, UK

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Sarah M Creighton Department of Women’s Health, University College London Hospital, London, UK

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Gerard S Conway Department of Women’s Health, University College London Hospital, London, UK

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during foetal development. Common clinical presentations include inguinal or labial hernia in childhood or primary amenorrhoea in adolescence ( 1 ). CAIS may also present through screening after a family member is affected or discordance between prenatal

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Annelies van’t Westeinde Department of Women’s and Children’s Health, Karolinska Institutet and Division of Pediatrics, Unit for Pediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, Stockholm, Sweden

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Leif Karlsson Department of Women’s and Children’s Health, Karolinska Institutet and Division of Pediatrics, Unit for Pediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, Stockholm, Sweden

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Valeria Messina Department of Women’s and Children’s Health, Karolinska Institutet and Division of Pediatrics, Unit for Pediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, Stockholm, Sweden

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Lena Wallensteen Department of Women’s and Children’s Health, Karolinska Institutet and Division of Pediatrics, Unit for Pediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, Stockholm, Sweden

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Manuela Brösamle European Patient Advocacy Group for Adrenal Diseases, European Reference Network on Rare Endocrine Conditions (Endo ERN), Endo ERN Coordinating Centre, Leiden, The Netherlands

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Giorgio Dal Maso ArfSAG (Associazione Refionale Famiglie Sindrome Adreno Genitale) c/o Unita Operativa di Pediatria, Azienda Ospedaliero Universitaria di Bologna, Policlinico S Orsala-Malpighi, Bologna, Italy

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Alessandro Lazzerini Spanish Association of Congenital Adrenal Hyperplasia (CAH), Spain

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Jette Kristensen ePAG & Chair of Danish Addison Patient Association, Aarhus, Denmark

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Diana Kwast Dutch Adrenal Society NVACP, Nijkerk, The Netherlands

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Lea Tschaidse Department of Endocrinology, Medizinische Klinik IV, Klinikum der Universität München, Munich, Germany

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Matthias K Auer Department of Endocrinology, Medizinische Klinik IV, Klinikum der Universität München, Munich, Germany

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Hanna F Nowotny Department of Endocrinology, Medizinische Klinik IV, Klinikum der Universität München, Munich, Germany

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Luca Persani Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy

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Nicole Reisch Department of Endocrinology, Medizinische Klinik IV, Klinikum der Universität München, Munich, Germany

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Svetlana Lajic Department of Women’s and Children’s Health, Karolinska Institutet and Division of Pediatrics, Unit for Pediatric Endocrinology and Metabolic Disorders, Karolinska University Hospital, Stockholm, Sweden

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childhood and even into adulthood, with potentially clinically relevant endpoints. We summarized potential points of interference and endpoints in Fig. 2 . The current review will focus mainly on brain development as most follow-up studies have focused on

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