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Jelena Stankovic Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Kurt Kristensen Steno Diabetes Center Aarhus (SDCA), Aarhus University Hospital, Aarhus, Denmark
Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark

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Niels Birkebæk Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark

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Jens Otto Lunde Jørgensen Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Esben Søndergaard Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
Steno Diabetes Center Aarhus (SDCA), Aarhus University Hospital, Aarhus, Denmark

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diagnosis of GHD in adults ( 12 , 13 ). Again, the underlying mechanism is considered to involve suppression of hypothalamic somatostatin ( 14 ). Furthermore, clonidine is used to diagnose GHD in children ( 15 ) and has been reported to inhibit AVP

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Kevin C J Yuen Departments of Neuroendocrinology and Neurosurgery, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, Arizona, United States

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Gudmundur Johannsson Department of Endocrinology, Sahlgrenska University Hospital and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Ken K Y Ho The Garvan Institute of Medical Research and the Faculty of Medicine, University of New South Wales, Sydney, Australia

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Bradley S Miller Pediatric Endocrinology, University of Minnesota Medical School, M Health Fairview Masonic Children’s Hospital, Minneapolis, Minnesota, United States

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Ignacio Bergada Centro de Investigaciones Endocrinológicas "Dr César Bergadá" (CEDIE), CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina

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Alan D Rogol Pediatric Diabetes and Endocrinology, University of Virginia, Charlottesville, Virginia, United States

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misclassifying those that were GH-sufficient ( 76 ) Performance not dependent on age, BMI, or sex ( 76 , 77 ) Clonidine ≤6.8 Used more commonly in children, but not in adults ( 83 , 84 ) ≤0.4 Relatively short over 90 min ( 85

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Anastasia Ibba SSD Endocrinologia Pediatrica e Centro Screening Neonatale, Ospedale Pediatrico Microcitemico, ‘A. Cao’, AO Brotzu, Cagliari, Italy

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Francesca Corrias SSD Endocrinologia Pediatrica e Centro Screening Neonatale, Ospedale Pediatrico Microcitemico, ‘A. Cao’, AO Brotzu, Cagliari, Italy

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Chiara Guzzetti SSD Endocrinologia Pediatrica e Centro Screening Neonatale, Ospedale Pediatrico Microcitemico, ‘A. Cao’, AO Brotzu, Cagliari, Italy

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Letizia Casula SSD Endocrinologia Pediatrica e Centro Screening Neonatale, Ospedale Pediatrico Microcitemico, ‘A. Cao’, AO Brotzu, Cagliari, Italy

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Mariacarolina Salerno Dipartimento di Pediatria, Università Federico II, Napoli, Italy

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Natascia di Iorgi Dipartimento di Pediatria, IRCCS Istituto Giannina Gaslini, Università di Genova, Genova, Italy
Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-infantili, Università di Genova, Genova, Italy

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Gianluca Tornese SSD Endocrinologia Pediatrica, Clinica Pediatrica, IRCCS Materno-infantile Burlo Garofolo, Trieste, Italy

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Giuseppa Patti Dipartimento di Pediatria, IRCCS Istituto Giannina Gaslini, Università di Genova, Genova, Italy
Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-infantili, Università di Genova, Genova, Italy

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Giorgio Radetti Dipartimento di Pediatria, Ospedale Generale Regionale, Bolzano, Italy

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Mohamad Maghnie Dipartimento di Pediatria, IRCCS Istituto Giannina Gaslini, Università di Genova, Genova, Italy
Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-infantili, Università di Genova, Genova, Italy

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Marco Cappa UOC di Endocrinologia, Dipartimento Universitario Ospedaliero, Ospedale Pediatrico Bambino Gesù IRCCS, Roma, Italy

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Sandro Loche SSD Endocrinologia Pediatrica e Centro Screening Neonatale, Ospedale Pediatrico Microcitemico, ‘A. Cao’, AO Brotzu, Cagliari, Italy

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; IGHD, idiopathic growth hormone deficiency; IGF1, insulin-like growth factor 1; OGHD, organic/genetic growth hormone deficiency; SDS, standard deviation score. Methods Clonidine and arginine stimulation tests and insulin tolerance test

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Taísa A R Vicente
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Ívina E S Rocha
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Roberto Salvatori Division of Endocrinology, Division of Endocrinology, National Research Council, Federal University of Sergipe, Aracaju, Sergipe 49060-100, Brazil

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Carla R P Oliveira
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Rossana M C Pereira
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Anita H O Souza
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Viviane C Campos
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Elenilde G Santos
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Rachel D C Araújo Diniz
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Eugênia H O Valença
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Carlos C Epitácio-Pereira
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Mario C P Oliveira
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Andrea Mari Division of Endocrinology, Division of Endocrinology, National Research Council, Federal University of Sergipe, Aracaju, Sergipe 49060-100, Brazil

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Manuel H Aguiar-Oliveira
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CR Prado CM Farias CT Almeida JC Vicente TA . Growth hormone (GH) response to hypoglycemia and clonidine in the GH-releasing hormone resistance syndrome . Journal of Endocrinological Investigation 2006 29 805 – 808 . 19 Laron Z

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Nathalie Ly Department of Endocrinology and Reproductive Medicine, Reference Center for Rare Endocrine Diseases of Growth and Development, Reference Center for Gynecological Rare Diseases, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France
EndoERN, APHP Consortium Pitie Salpetriere Hospital, Necker Hospital, Paris, France

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Sophie Dubreuil Department of Endocrinology and Reproductive Medicine, Reference Center for Rare Endocrine Diseases of Growth and Development, Reference Center for Gynecological Rare Diseases, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France
EndoERN, APHP Consortium Pitie Salpetriere Hospital, Necker Hospital, Paris, France

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Philippe Touraine Department of Endocrinology and Reproductive Medicine, Reference Center for Rare Endocrine Diseases of Growth and Development, Reference Center for Gynecological Rare Diseases, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris, France
EndoERN, APHP Consortium Pitie Salpetriere Hospital, Necker Hospital, Paris, France
Sorbonne University, Paris, France

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Lunenfeld B Brandes JM . Synergistic effect of growth hormone and gonadotropins in achieving conception in ‘clonidine-negative’ patients with unexplained infertility . Annals of the New York Academy of Sciences 1991 626 250 – 265 . ( https://doi.org/10

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Elena Galazzi IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy
Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy

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Paolo Duminuco IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy

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Mirella Moro IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy

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Fabiana Guizzardi IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy

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Nicoletta Marazzi IRCSS Istituto Auxologico Italiano, Laboratory for Auxo-Endocrinological Research, Milan, Italy

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Alessandro Sartorio IRCSS Istituto Auxologico Italiano, Laboratory for Auxo-Endocrinological Research, Milan, Italy
Division of Auxology and Metabolic Diseases, IRCSS Istituto Auxologico Italiano, Piancavallo (VB), Italy

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Sabrina Avignone Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, U.O.C Neuroradiologia, Milan, Italy

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Marco Bonomi IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy
Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy

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Luca Persani IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy
Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy

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Maria Teresa Bonati IRCCS Istituto Auxologico Italiano, Service of Medical Genetics, Milan, Italy

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-thyroid antibodies. The proband’s sister had normal menses but exhibited absence of the right breast and moderate hypoplasia of the left one at ultrasound. She had been diagnosed with idiopathic GH deficiency (GH peak was blunted either after clonidine or insulin

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Lukas Plachy Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Petra Dusatkova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Klara Maratova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Shenali Anne Amaratunga Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Dana Zemkova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Vit Neuman Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Stanislava Kolouskova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Barbora Obermannova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Marta Snajderova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Zdenek Sumnik Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Jan Lebl Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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Stepanka Pruhova Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Úvalu, Prague, Czech Republic

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auxological and/or other clinical features suggestive of GHD ( 14 ) and IGF-1 concentration <0 s.d. (reference ranges standardized for age and sex), GHD was confirmed by GH stimulation tests. Two different stimulation tests (clonidine and insulin hypoglycemia

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Marko Stojanovic Neuroendocrinology Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia
University of Belgrade, Medical Faculty, Belgrade, Serbia

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Zida Wu Department of Medicine for Endocrinology, Diabetes and Nutritional Medicine, Charité Universitätsmedizin, Campus Mitte, Berlin, Germany

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Craig E Stiles Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Dragana Miljic Neuroendocrinology Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia
University of Belgrade, Medical Faculty, Belgrade, Serbia

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Ivan Soldatovic University of Belgrade, Medical Faculty, Belgrade, Serbia
Insitute of Medical Statistics and Informatics, Belgrade, Serbia

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Sandra Pekic Neuroendocrinology Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia
University of Belgrade, Medical Faculty, Belgrade, Serbia

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Mirjana Doknic Neuroendocrinology Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia
University of Belgrade, Medical Faculty, Belgrade, Serbia

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Milan Petakov Neuroendocrinology Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia
University of Belgrade, Medical Faculty, Belgrade, Serbia

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Vera Popovic University of Belgrade, Medical Faculty, Belgrade, Serbia

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Christian Strasburger Department of Medicine for Endocrinology, Diabetes and Nutritional Medicine, Charité Universitätsmedizin, Campus Mitte, Berlin, Germany

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Márta Korbonits Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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– 854 . ( https://doi.org/10.1161/ATVBAHA.114.304539 ) 25767277 10.1161/ATVBAHA.114.304539 40 Salvatori R Serpa MG Parmigiani G Britto AV Oliveira JL Oliveira CR Prado CM Farias CT Almeida JC Vicente TA , GH response to hypoglycemia and clonidine in

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Werner F Blum University Children’s Hospital, Giessen, Germany

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Abdullah Alherbish Al Habib Medical Group, Riyadh, Saudi Arabia

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Afaf Alsagheir King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

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Ahmed El Awwa Department of Pediatric Endocrinology & Diabetes, Hamad Medical Center, Doha, Qatar

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Walid Kaplan Tawam Hospital, Al Ain, UAE

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Ekaterina Koledova Global Medical Affairs Endocrinology, Merck KGaA, Darmstadt, Germany

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Martin O Savage William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, London, UK

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<10 μg/L, should always be supported by auxological evidence of subnornal growth velocity. The GH stimulation tests currently recommended for paediatric patients include glucagon, clonidine, arginine or GHRH plus arginine. Interpretation of peak GH

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Nathalia G B P Ferreira Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

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Joao L O Madeira Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

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Peter Gergics Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil

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Renata Kertsz Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

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Juliana M Marques Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

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Nicholas S S Trigueiro Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

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Anna Flavia Figueredo Benedetti University of Michigan Medical School, Department of Human Genetics, Ann Arbor, Michigan, United States

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Bruna V Azevedo Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

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Bianca H V Fernandes Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil
Universidade de São Paulo, Zebrafish Facility, São Paulo, São Paulo, Brazil

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Debora D Bissegatto Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

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Isabela P Biscotto Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

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Qing Fang Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil

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Qianyi Ma Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil

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Asye B Ozel Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil

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Jun Li Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil

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Sally A Camper Laboratório de Sequenciamento em Larga Escala (SELA), Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil

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Alexander A L Jorge Unidade de Endocrinologia Genética, Laboratório de Endocrinologia Celular e Molecular LIM25, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

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Berenice B Mendonça Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

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Ivo J P Arnhold Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

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Luciani R Carvalho Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Disciplina de Endocrinologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil

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(FSH), tri-iodothyronine, thyroxine (T 4 ), free T 4 , dehydroepiandrosterone sulfate, estradiol, or testosterone were measured at baseline as previously described ( 7 ). Clonidine and combined pituitary stimulation tests (0.05–0.1 U/kg insulin, 200 μg

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