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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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C Varricchio M . Serum levels of insulin-like growth factor-I (IGF1) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function . Journal of Clinical

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A V Dreval
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I V Trigolosova
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I V Misnikova
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Y A Kovalyova
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R S Tishenina
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I A Barsukov
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A V Vinogradova
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B H R Wolffenbuttel Moscow Regional Scientific Research Clinical Institute, Department of Endocrinology, 61/2 Shepkina str., 129110 Moscow, Russia

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Mandarino L Kashyap S Belfort R DeFronzo RA . Effect of IGF-I on FFA and glucose metabolism in control and type 2 diabetic subjects . American Journal of Physiology. Endocrinology and Metabolism 2002 282 E1360 – E1368 . ( doi:10.1152/ajpendo

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Alexander A L Jorge Unidade de Endocrinologia-Genetica, LIM/25, Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, Brazil

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Thomas Edouard Endocrine, Bone Diseases, and Genetics Unit, Children’s Hospital, Toulouse University Hospital, RESTORE INSERM UMR1301, Toulouse, France

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Mohamad Maghnie Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genova, Italy
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy

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Alberto Pietropoli Novo Nordisk Health Care AG, Global Medical Affairs Biopharm, Zürich, Switzerland

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Nicky Kelepouris Novo Nordisk Inc., Clinical, Medical and Regulatory Biopharm-RED, Plainsboro, New Jersey, USA

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Alicia Romano Department of Pediatrics, New York Medical College, Valhalla, New York, USA

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Martin Zenker Institute of Human Genetics & Department of Pediatrics, University Hospital, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

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Reiko Horikawa Department of Endocrine and Metabolism, National Center for Child Health and Development, Tokyo, Japan

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factor I (IGF-I) level, and bone age. Adverse drug reactions (ADR), serious ADRs (SADR), and serious adverse events (SAE) were recorded for all patients throughout the duration of treatment. The GHLIQUID-4020 trial was a 4-year multicenter, randomized

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Rachel D C A Diniz
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Renata M Souza
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Roberto Salvatori Division of Endocrinology, Division of Endocrinology, Division of Hepatology, Division of Radiology, Diabetes and Metabolism, Federal University of Sergipe, Aracaju, Brazil

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Alex Franca Division of Endocrinology, Division of Endocrinology, Division of Hepatology, Division of Radiology, Diabetes and Metabolism, Federal University of Sergipe, Aracaju, Brazil

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Elenilde Gomes-Santos
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Thiago O Ferrão Division of Endocrinology, Division of Endocrinology, Division of Hepatology, Division of Radiology, Diabetes and Metabolism, Federal University of Sergipe, Aracaju, Brazil

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Carla R P Oliveira
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João A M Santana
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Francisco A Pereira
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Rita A A Barbosa
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Anita H O Souza
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Rossana M C Pereira
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Alécia A Oliveira-Santos
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Allysson M P Silva
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Francisco J Santana-Júnior
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Eugênia H O Valença
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Viviane C Campos
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Manuel H Aguiar-Oliveira
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, accelerated atherosclerosis, and increased cardiovascular mortality (9) . AOGHD has been associated with NAFLD (10, 11, 12) . Some of the effects of GH are mediated by circulating IGF1, which is mostly of liver origin. IGF1 circulates bound to six IGF1

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Robert Rapaport Division of Pediatric Endocrinology & Diabetes, Mount Sinai Kravis Children’s Hospital and Icahn School of Medicine at Mount Sinai, New York, New York, USA

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Jan M Wit Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands

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

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in the child or parents has been identified. However, since the discovery that most genes associated with growth have no direct relationship with the GH–IGF-I axis ( 9 ), it appears more useful to think in terms of another conceptual framework for

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Kennett Sprogøe Ascendis Pharma A/S, Hellerup, Denmark

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Eva Mortensen Ascendis Pharma, Inc., Palo Alto, California, USA

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David B Karpf Ascendis Pharma, Inc., Palo Alto, California, USA

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Jonathan A Leff Ascendis Pharma, Inc., Palo Alto, California, USA

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identified, including (i) supraphysiological elevations of GH and/or IGF-1, (ii) trough GH concentrations above normal physiological levels, (iii) fluctuating IGF-1 levels, (iv) elevated IGF-1 in the absence of GH bioactivity, (v) nonphysiological tissue

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Maria Cristina De Martino Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

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Richard A Feelders Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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Claudia Pivonello Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

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Chiara Simeoli Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

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Fortuna Papa Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

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Annamaria Colao Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

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Rosario Pivonello Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

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Leo J Hofland Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

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and drugs targeting the IGF pathway in ACCs. These results are in line with a recently published phase I study demonstrating that a subgroup (about 40%) of ACC patients treated with cixutumumab (IGF1R inhibitor) and temsirolimus (mTOR inhibitor

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Charlotte Höybye Patient Area Endocrinology and Nephrology, Infection and Inflammation Theme, Karolinska University Hospital, Stockholm, Sweden
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden

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Laia Faseh Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden

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Christos Himonakos Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
Department of Medicine, Karlstad Hospital, Karlstad, Sweden

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Tomasz Pielak NUTOPI Sp. z o. o., Poznan, Poland

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Jesper Eugen-Olsen Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark

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. Doses were individually titrated to insulin-like growth factor I (IGF-I) levels in age-matched healthy subjects. Clinical examinations and sampling of fasting routine blood tests were performed at scheduled visits to the clinic and in addition 2 mL serum

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

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

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Stephen J Rose Birmingham Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

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Talat Mushtaq The Leeds Teaching Hospital NHS Trust, Leeds, UK

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Avinaash V Maharaj Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK

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

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Martin O Savage Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK

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Louise A Metherell Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK

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Helen L Storr Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK

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.5 −2.5 OBSL1 Het c.2671A>G, p.T891A Missense Damaging Probably damaging 26.8 Uncertain significance 6 1.2 −4.4 −2.2 IGF1R Het c.109_123dupATCGACATCCGCAAC, p.I37_N41dup In-frame NK NK NK Uncertain significance 7

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Lisa Arnetz Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes
Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes

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Neda Rajamand Ekberg Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes
Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes

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Kerstin Brismar Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes
Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes

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Michael Alvarsson Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes
Departments of Endocrinology, Molecular Medicine and Surgery, Metabolism and Diabetes

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of Clinical Endocrinology and Metabolism 1994 78 960 – 967 . ( doi:10.1210/jcem.78.4.7512573 ). 15 Brugts MP van Duijn CM Hofland LJ Witteman JC Lamberts SW Janssen JA . Igf-I bioactivity in an elderly population: relation to

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