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María Dolores Rodríguez Arnao Pediatric Endocrinology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Amparo Rodríguez Sánchez Pediatric Endocrinology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Ignacio Díez López Hospital Universitario Araba, Araba/Alava, Spain

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Joaquín Ramírez Fernández Hospital Universitario Príncipe de Asturias, Oviedo, Spain

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Jose Antonio Bermúdez de la Vega Centro Nuevas Tecnologias, Sevilla, Spain

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Diego Yeste Fernández Hospital Vall d’Hebrón, Barcelona, Spain

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María Chueca Guindulain Complejo Hospitalario de Navarra, Pamplona, Spain

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Raquel Corripio Collado Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain

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Jacobo Pérez Sánchez Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain

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Ana Fernández González Merck S.L.U., Madrid, Spain

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ECOS Spain Study Collaborative Investigator Group
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Introduction Since the 60s, GH has been the mainstay of treatment for children with GH deficiency (GHD) ( 1 ). With the discovery of recombinant human growth hormone (r-hGH), the treatment has been extended to other conditions, such as Turner

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Pinaki Dutta
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Bhuvanesh Mahendran Department of Endocrinology, Internal Medicine, Cardiology, Hematology, Histopathology, Gastroenterology, Neurosurgery, Pharmacology, Radiodiagnosis, 4th Floor, F Block, Post Graduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India

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K Shrinivas Reddy Department of Endocrinology, Internal Medicine, Cardiology, Hematology, Histopathology, Gastroenterology, Neurosurgery, Pharmacology, Radiodiagnosis, 4th Floor, F Block, Post Graduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India

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Jasmina Ahluwalia Department of Endocrinology, Internal Medicine, Cardiology, Hematology, Histopathology, Gastroenterology, Neurosurgery, Pharmacology, Radiodiagnosis, 4th Floor, F Block, Post Graduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India

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Kim Vaiphei Department of Endocrinology, Internal Medicine, Cardiology, Hematology, Histopathology, Gastroenterology, Neurosurgery, Pharmacology, Radiodiagnosis, 4th Floor, F Block, Post Graduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India

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Rakesh K Kochhar Department of Endocrinology, Internal Medicine, Cardiology, Hematology, Histopathology, Gastroenterology, Neurosurgery, Pharmacology, Radiodiagnosis, 4th Floor, F Block, Post Graduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India

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Prakamya Gupta Department of Endocrinology, Internal Medicine, Cardiology, Hematology, Histopathology, Gastroenterology, Neurosurgery, Pharmacology, Radiodiagnosis, 4th Floor, F Block, Post Graduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India

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Anand Srinivasan Department of Endocrinology, Internal Medicine, Cardiology, Hematology, Histopathology, Gastroenterology, Neurosurgery, Pharmacology, Radiodiagnosis, 4th Floor, F Block, Post Graduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India

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Mahesh Prakash Department of Endocrinology, Internal Medicine, Cardiology, Hematology, Histopathology, Gastroenterology, Neurosurgery, Pharmacology, Radiodiagnosis, 4th Floor, F Block, Post Graduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India

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Kanchan Kumar Mukherjee Department of Endocrinology, Internal Medicine, Cardiology, Hematology, Histopathology, Gastroenterology, Neurosurgery, Pharmacology, Radiodiagnosis, 4th Floor, F Block, Post Graduate Institute of Medical Education and Research, Nehru Hospital, Chandigarh 160012, India

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Viral N Shah
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Girish Parthan
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Anil Bhansali
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hormones are intact or properly replaced (4, 5, 6) . In addition, GH replacement in these subjects has been shown to reverse many of the abnormalities (7) . There is a paucity of data on recombinant human GH (r-hGH) replacement therapy in acromegaly

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Jessica S Jarmasz Department of Physiology & Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

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Yan Jin Department of Physiology & Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

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Hana Vakili Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

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Peter A Cattini Department of Physiology & Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

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Introduction Human (h) growth hormone (GH) is synthesized and secreted in a pulsatile manner by somatotrophs located in the anterior pituitary ( 1 ). Following the successful isolation and purification of hGH in 1944, GH secretion in humans

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Juliane Léger Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Service d’Endocrinologie Diabétologie Pédiatrique, Centre de Référence des Maladies Endocriniennes de la Croissance et du développement, Paris, France
Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1141, DHU PROTECT, Paris, France

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Anne Fjellestad-Paulsen Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Service d’Endocrinologie Diabétologie Pédiatrique, Centre de Référence des Maladies Endocriniennes de la Croissance et du développement, Paris, France

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Anne Bargiacchi Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Service de Psychiatrie de l’Enfant et de l’Adolescent, Centre de Référence des Maladies Endocriniennes de la Croissance et du développement, Paris, France

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Catherine Doyen Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Service de Psychiatrie de l’Enfant et de l’Adolescent, Centre de Référence des Maladies Endocriniennes de la Croissance et du développement, Paris, France

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Emmanuel Ecosse Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Service d’Endocrinologie Diabétologie Pédiatrique, Centre de Référence des Maladies Endocriniennes de la Croissance et du développement, Paris, France

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Jean-Claude Carel Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Service d’Endocrinologie Diabétologie Pédiatrique, Centre de Référence des Maladies Endocriniennes de la Croissance et du développement, Paris, France
Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 1141, DHU PROTECT, Paris, France

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Marie-France Le Heuzey Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Service de Psychiatrie de l’Enfant et de l’Adolescent, Centre de Référence des Maladies Endocriniennes de la Croissance et du développement, Paris, France

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are at least partially reversed during refeeding and recovery ( 19 ). The effects of supraphysiological levels of human GH on HV in these patients remain unclear. The administration of supraphysiological doses of hGH for four weeks is well tolerated

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Ichelle Maa van Roessel Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, University Medical Center Utrecht, AB Utrecht, The Netherlands
Princess Máxima Center for Pediatric Oncology, AB Utrecht, The Netherlands

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Boudewijn Bakker Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, University Medical Center Utrecht, AB Utrecht, The Netherlands
Princess Máxima Center for Pediatric Oncology, AB Utrecht, The Netherlands

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Hanneke M van Santen Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, University Medical Center Utrecht, AB Utrecht, The Netherlands
Princess Máxima Center for Pediatric Oncology, AB Utrecht, The Netherlands

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Wassim Chemaitilly Division of Pediatric Endocrinology, UPMC Children’s Hospitalof Pittsburgh, Pittsburgh, Pennsylvania, USA

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Guidelines ( 2 ). The treatment of GH deficiency relies on the use of human recombinant GH (hGH). This allows affected children to improve their linear growth and achieve better final height outcomes with added benefits on bone health, lean body mass and

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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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to rhGH. Genetic identification of IGF1R defects can be compared to published experience of rhGH therapy in such patients ( 73 ) rather than to non-specific responses to hGH in idiopathic SGA subjects. The new development of C-type natriuretic

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Niels B Dalsgaard Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Lærke S Gasbjerg Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Laura S Hansen Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

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Dennis S Nielsen Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark

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Torben S Rasmussen Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark

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Filip K Knop Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Gentofte, Denmark

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Committee of the Capital Region of Denmark (record no. H-17007893). The study was registered at clinicaltrials.gov (ID: NCT03241303) and the Danish Data Protection Agency (local no. HGH-2018-041, I-Suite no. 6.802). Research design and experimental

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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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://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004975-37/results ) 66 Kang J Kim P Kwak EH Xu M-Y Han O Kim Y Jung SY Kwon S Huh Y Chapel S . 6 month results of a phase II, randomized, active controlled, open label study of safety and efficacy of HM10560A a long acting r-Hgh-HMbib1

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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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significant. GraphPad Prism 7.0 software and R Core Team software (Vienna, Austria) were used to perform those analysis. Results Population description and GHD status Between March 2006 and January 2022, 156 GHD female patients presented with GHD

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Justyna Modrzynska Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Christine F Klein Department of Cardiology, Herlev Gentofte Hospital, Herlev, Denmark

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Kasper Iversen Department of Clinical Medicine, Herlev Gentofte Hospital, Herlev, Denmark

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Henning Bundgaard Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Bolette Hartmann Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Maike Mose Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Nikolaj Rittig Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

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Niels Møller Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark

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Jens J Holst Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Nicolai J Wewer Albrechtsen Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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surgery within 14 days prior to the study inclusion were excluded from the study population. All patients provided written informed consent. The study protocol was approved by the Data Protection Agency (HGH-2015-010, I-suite no: 03923) and the Danish

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