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Stephanie E Baldeweg Department of Endocrinology, University College Hospital, London, UK
National Hospital for Neurology and Neurosurgery, London, UK

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Mark Vanderpump Physicians’ Clinic, London, UK

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Will Drake Department of Endocrinology, St Bartholomew’s Hospital, London, UK

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Narendra Reddy Endocrinology/General Medicine, University Hospitals Coventry and Warwickshire NHS Trust, University of Warwick, Coventry, UK

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Andrew Markey The Lister Hospital, London, UK

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Gordon T Plant Department of Endocrinology, University College Hospital, London, UK
National Hospital for Neurology and Neurosurgery, London, UK

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Michael Powell National Hospital for Neurology and Neurosurgery, London, UK

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Saurabh Sinha Royal Hallamshire Hospital, Sheffield, UK

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John Wass Department of Endocrinology, Oxford Centre for Diabetes Endocrinology and Metabolism, The Churchill, Oxford University, Oxford, UK

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the Society for Endocrinology Clinical Committee The Society for Endocrinology, 22 Apex Court, Woodlands, Bradley Stoke, Bristol, UK

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Careful assessment of fluid and electrolyte balance Ideally, endocrine evaluation with blood samples for random serum cortisol, TSH, free T 4 , prolactin, IGF1, LH, FSH, testosterone (men), oestradiol (women) for later analysis Bedside assessment of

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Xiaohui Qi Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Ping He Shanghai Hospital Link Center, Shanghai Hospital Development Center, Shanghai, China

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Huayan Yao Computer Net Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Huanhuan Sun Wonders Information Co. Ltd, Shanghai, China

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Jiying Qi Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Min Cao Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Bin Cui Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Guang Ning Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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because it is structurally modified ( 20 , 21 ). In addition to activating the insulin receptor cascade response, long-acting insulin analogs can also affect the IGF-1 receptor cascade response ( 22 ). And there is evidence from Alvaro’s study that IGF-1

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Esben Thyssen Vestergaard Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark
Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark
Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Morten B Krag Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Morten M Poulsen Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Steen B Pedersen Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Niels Moller Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark
Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Jens Otto Lunde Jorgensen Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark
Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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Niels Jessen Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark
Medical Research Laboratories, Department of Endocrinology and Diabetes, Department of Pediatrics, Department of Endocrinology and Diabetes, Institute of Clinical Medicine, Aarhus University, Norrebrogade 44, DK-8000 Aarhus C, Denmark

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an arginine stimulation test ( n =1) with a GH cutoff level ≤3 μg/l. BMI was between 27.5 and 36.0 kg/m 2 and insulin-like growth factor 1 (IGF1) concentrations were within the normal range. Each subject was examined twice in a randomized, double

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Johan Verhelst Department of Endocrinology, ZNA Middelheim Hospital, Antwerp, Belgium

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Anders F Mattsson Pfizer Endocrine Care, Pfizer Health AB, Sollentuna, Sweden

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Cecilia Camacho-Hübner Pfizer Endocrine Care, Pfizer, Inc., New York, New York, USA

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Anton Luger Division of Endocrinology and Metabolism, Medical University and General Hospital, Vienna, Austria

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Roger Abs Antwerp Centre for Endocrinology, Antwerp, Belgium

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changes in BMI, IGF1 SDS, QoL-AGHDA, MetS score and MetS components are reported in Table 1 . Noteworthy is the finding that the dissimilarity in response was not related to a different baseline IGF1 SDS, GH replacement dose or IGF1 SDS at Y1, while a

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Elena Valassi Endocrinology/Medicine Department, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

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Natalia García-Giralt URFOA, IMIM (Institut Hospital del Mar d’Investigacions Mèdiques), Universitat Autònoma de Barcelona, Barcelona, Spain

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Jorge Malouf Mineral Metabolism Unit, Medicine Department, Hospital Sant Pau, Barcelona, Spain

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Iris Crespo Endocrinology/Medicine Department, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

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Jaume Llauger Radiology Department, Hospital Sant Pau, Barcelona, Spain

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Adolfo Díez-Pérez URFOA, IMIM (Institut Hospital del Mar d’Investigacions Mèdiques), Universitat Autònoma de Barcelona, Barcelona, Spain

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Susan M Webb Endocrinology/Medicine Department, Hospital Sant Pau, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, Unidad 747), IIB-Sant Pau, ISCIII and Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

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Introduction Growth hormone (GH) and insulin-like growth factor-I (IGF1) are anabolic hormones which influence bone metabolism through the modulation of several signaling pathways ( 1 ). In vitro studies showed that GH enhances the

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Laura van Iersel Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

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Sarah C Clement Department of Pediatrics, Amsterdam University Medical Center, location VU University Medical Center, Amsterdam, The Netherlands

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Antoinette Y N Schouten-van Meeteren Department of Pediatric Oncology, Emma Children’s Hospital, Amsterdam University Medical Center, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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Annemieke M Boot Department of Pediatric Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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Hedi L Claahsen-van der Grinten Department of Pediatric Endocrinology, Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands

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Bernd Granzen Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands

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K Sen Han Department of Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands

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Geert O Janssens Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands

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Erna M Michiels Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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A S Paul van Trotsenburg Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Center, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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W Peter Vandertop Neurosurgical Center Amsterdam, Amsterdam University Medical Center, location Academic Medical Center, University of Amsterdam and location VU University Medical Center, Amsterdam, The Netherlands

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Dannis G van Vuurden Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Department of Pediatric Oncology/Hematology, Amsterdam University Medical Center, location VU University Medical Center, Amsterdam, The Netherlands

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Hubert N Caron Department of Pediatric Oncology, Emma Children’s Hospital, Amsterdam University Medical Center, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

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Leontien C M Kremer Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Department of Pediatrics, Emma Children’s Hospital, Amsterdam University Medical Center, location Academic Medical Center, University of Amsterdam, Amsterdam, 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

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 mU/L in combination with an insulin-like growth factor-1 (IGF1) concentration <−2 standard deviation score (SDS). The date of GHD diagnosis was recorded as the date that the last GH stimulation test was performed to establish GHD diagnosis

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Henrik H Thomsen Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Holger J Møller Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Christian Trolle Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Kristian A Groth Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Anne Skakkebæk Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Anders Bojesen Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Christian Høst Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Claus H Gravholt Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark
Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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commercial RIA (Linco, St Louis, MO, USA). Total insulin-like growth factor 1 (IGF1) was measured by use of in-house noncompetitive, TR-IFMAs after acid–ethanol extraction of serum as described (30) . C-reactive protein (CRP) was measured by an

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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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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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mTOR pathways. The relationship between the mTOR- and the IGF pathways in the NCI-H295R and SW13 ACC cell lines is addressed in a few studies ( 24 , 28 ). These studies demonstrate that both ACC cell lines have a similar protein expression of IGF1R

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Nannan Bian Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

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Xiaomeng Sun Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

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Biao Zhou Departments of General Surgery and Obesity and Metabolic Disease Center, China-Japan Friendship Hospital, Beijing, China

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Lin Zhang Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

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Qiu Wang Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

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Yu An Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

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Xiaohui Li Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

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Yinhui Li Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

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Jia Liu Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

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Hua Meng Departments of General Surgery and Obesity and Metabolic Disease Center, China-Japan Friendship Hospital, Beijing, China

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Guang Wang Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

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). Crosstalk between cell-surface GPCRs and receptor tyrosine kinases (RTKs) is a pervasive phenomenon ( 38 ). The insulin-like growth factor 1 receptor (IGF1R) is an RTK shown to have crosstalk with TSHR in brow fat and orbital fat of patients with thyroid

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