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Elena V Varlamov Department of Medicine (Endocrinology, Diabetes and Clinical Nutrition), Oregon Health & Science University, Portland, Oregon, USA
Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon, USA
Pituitary Center, Oregon Health & Science University, Portland, Oregon, USA

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Dan Alexandru Niculescu Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon, USA

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Swechya Banskota Department of Medicine (Endocrinology, Diabetes and Clinical Nutrition), Oregon Health & Science University, Portland, Oregon, USA
Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon, USA
Pituitary Center, Oregon Health & Science University, Portland, Oregon, USA

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Simona Andreea Galoiu Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon, USA

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Catalina Poiana Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon, USA

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Maria Fleseriu Department of Medicine (Endocrinology, Diabetes and Clinical Nutrition), Oregon Health & Science University, Portland, Oregon, USA
Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon, USA
Pituitary Center, Oregon Health & Science University, Portland, Oregon, USA

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comorbidities related to the tumor itself (e.g. headache, oculomotor never palsy or hypopituitarism) or to GH and insulin-like growth factor-1 (IGF-1) excess (arthralgia, morphologic changes, or obstructive sleep apnea (OSA), cardiovascular disease, and

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Xiaonan Guo Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

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Wenjing Hu Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

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Xiaorui Lyu Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

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Hanyuan Xu Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

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Huijuan Zhu Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

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Hui Pan Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

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Linjie Wang Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

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Hongbo Yang Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

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Fengying Gong Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

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Introduction Growth hormone (GH) is a significant regulator of growth and metabolism ( 1 ). In the liver, GH stimulates the synthesis and secretion of insulin-like growth factor 1 (IGF-1) ( 2 ). The GH/IGF-1 axis can regulate hepatic glucose

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R C S van Adrichem
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L J Hofland
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R A Feelders
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M C De Martino
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P M van Koetsveld
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C H J van Eijck Department of Internal Medicine, Department of Surgery, Department of Pathology, Sector of Endocrinology, Erasmus MC, ‘s Gravendijkwal 230, Room D-430, 3015 CE Rotterdam, The Netherlands

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R R de Krijger Department of Internal Medicine, Department of Surgery, Department of Pathology, Sector of Endocrinology, Erasmus MC, ‘s Gravendijkwal 230, Room D-430, 3015 CE Rotterdam, The Netherlands

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D M Sprij-Mooij
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J A M J L Janssen
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W W de Herder
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functions in normal tissues and tumors, plays an important role in the pathophysiology of GEP NETs (2) . The IGF system consists of different IGF-related genes: two ligands (IGF1 and IGF2), two IGF receptors (IGF1R and IGF2R), two insulin receptors (IR

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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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Introduction GH regulates β-cell function (βCF) and insulin sensitivity (IS) both directly and via complex interactions with its principal mediator, insulin-like growth factor 1 (IGF1) (1) . While GH reduces IS, IGF1 increases it. The hyperglycemic

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Sofia S Pereira Department of Anatomy and UMIB (Unit for Multidisciplinary Biomedical Research) of ICBAS, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Department of Endocrinology, University of Porto, Porto, 4050-313, Portugal
Department of Anatomy and UMIB (Unit for Multidisciplinary Biomedical Research) of ICBAS, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Department of Endocrinology, University of Porto, Porto, 4050-313, Portugal

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Tiago Morais Department of Anatomy and UMIB (Unit for Multidisciplinary Biomedical Research) of ICBAS, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Department of Endocrinology, University of Porto, Porto, 4050-313, Portugal

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Madalena M Costa Department of Anatomy and UMIB (Unit for Multidisciplinary Biomedical Research) of ICBAS, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Department of Endocrinology, University of Porto, Porto, 4050-313, Portugal

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Mariana P Monteiro Department of Anatomy and UMIB (Unit for Multidisciplinary Biomedical Research) of ICBAS, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Department of Endocrinology, University of Porto, Porto, 4050-313, Portugal

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Duarte Pignatelli Department of Anatomy and UMIB (Unit for Multidisciplinary Biomedical Research) of ICBAS, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Department of Endocrinology, University of Porto, Porto, 4050-313, Portugal
Department of Anatomy and UMIB (Unit for Multidisciplinary Biomedical Research) of ICBAS, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Department of Endocrinology, University of Porto, Porto, 4050-313, Portugal

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proliferation (Ki-67), and cell adhesion (E-cadherin and β-catenin), and the growth factor IGF2 and its receptor IGF1R. Subjects and methods Patients and tumors Paraffin-embedded adrenal samples from a total of 43 patients were used. These included ACA samples

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Melissa Braga Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA

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Zena Simmons Department of Health & Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA

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Keith C Norris Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

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Monica G Ferrini Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
Department of Health & Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

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Jorge N Artaza Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
Department of Health & Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

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). Mouse gene PCR primer sets (RT 2 ) for VDR, IGF1, IGF2, FGF1, FGF2, MSTN and FST were obtained from SABiosciences. The Power SYBR green PCR Master Mix (Applied Biosystems) was used with Step-One-Plus real-time PCR System (Applied Biosystems). The

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Laurent Maïmoun Département de Médecine Nucléaire, Hôpital Lapeyronie, Centre Hospitalier Régional Universitaire (CHU) Montpellier, Montpellier, France
PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France

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Denis Mariano-Goulart Département de Médecine Nucléaire, Hôpital Lapeyronie, Centre Hospitalier Régional Universitaire (CHU) Montpellier, Montpellier, France
PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France

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Helena Huguet Unité de Recherche Clinique et Epidémiologie, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France

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Eric Renard Departement d’Endocrinologie, Diabète, Nutrition, Hôpital Lapeyronie, CHRU Montpellier, Montpellier, France
CIC INSERM 1411, Hôpital Gui de Chauliac, CHU Montpellier, Montpellier Cedex 5, France
Institut de Génomique Fonctionnelle, CNRS UMR 5203/INSERM U661/Université Montpellier, Montpellier, France

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Patrick Lefebvre Departement d’Endocrinologie, Diabète, Nutrition, Hôpital Lapeyronie, CHRU Montpellier, Montpellier, France

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Marie-Christine Picot Unité de Recherche Clinique et Epidémiologie, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France
CIC INSERM 1411, Hôpital Gui de Chauliac, CHU Montpellier, Montpellier Cedex 5, France

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Anne-Marie Dupuy Département de Biochimie, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France

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Jean-Paul Cristol PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France
Département de Biochimie, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France

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Philippe Courtet Institut de Génomique Fonctionnelle, CNRS, INSERM Université Montpellier, Montpellier, France
Département d’Urgence et Post-Urgence Psychiatrique, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France

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Vincent Boudousq Département de Médecine Nucléaire, Hôpital Carémeau, CHU Nîmes, Nîmes, France

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Antoine Avignon Département Endocrinologie, Nutrition, Diabète, Equipe Nutrition, Diabète, CHU Montpellier, Montpellier, France

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Sébastien Guillaume Institut de Génomique Fonctionnelle, CNRS, INSERM Université Montpellier, Montpellier, France
Département d’Urgence et Post-Urgence Psychiatrique, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France

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Ariane Sultan PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France
Département Endocrinologie, Nutrition, Diabète, Equipe Nutrition, Diabète, CHU Montpellier, Montpellier, France

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these bone characteristics may explain the increased fracture risk observed in this population ( 7 ). Various endocrine and metabolic disturbances, including hypothyroidism ( 8 ), hypogonadism ( 1 , 9 , 10 ), hypercortisolism ( 2 , 11 ) and IGF-1

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Anastasia P Athanasoulia-Kaspar Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany

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Matthias K Auer Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany

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Günter K Stalla Clinical Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany

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Mira Jakovcevski Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany

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.95 35.05 n.a. n.a. n.a. n.a. n.a. White blood cell count (×10 9 /L) 108 7 6.24 1.35 n.a. n.a. n.a. n.a. n.a. IGF-1-SDS (ng/mL) 100 15 136.75 72.99 n.a. n.a. n.a. n.a. n.a. GHD, growth

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Anna Kistner Women and Child Health, Karolinska Institutet, SE-171 76 Stockholm, Sweden

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Mireille Vanpée Women and Child Health, Karolinska Institutet, SE-171 76 Stockholm, Sweden

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Kerstin Hall Women and Child Health, Karolinska Institutet, SE-171 76 Stockholm, Sweden

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are conflicting concerning leptin levels (5, 17, 18, 19) but elevated levels have been observed in prepubertal SGA children with catch-up growth (19) . IGF-binding protein-1 (IGFBP1) modulates the effect of IGF1 at target tissue. IGFBP1 levels are

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Lukas Plachy Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Lenka Petruzelkova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Petra Dusatkova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Klara Maratova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Dana Zemkova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Lenka Elblova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Vit Neuman Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Stanislava Kolouskova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Barbora Obermannova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Marta Snajderova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Zdenek Sumnik Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Jan Lebl Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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Stepanka Pruhova Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic

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and HESX1 ) that could cause FSS and multiple pituitary hormone deficiency ( 14 , 15 ). Insensitivity to GH (IGF deficiency and IGF resistance) may also be inherited in an AD manner (e.g., IGF1R , GHR and STAT5B genes) ( 2 , 16 ). Despite the

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