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Nelma Veronica Marques Neuroendocrinology Research Center, Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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Luiz Eduardo Armondi Wildemberg Neuroendocrinology Research Center, Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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Monica R Gadelha Neuroendocrinology Research Center, Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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normalising insulin-like growth factor 1 (IGF1) levels that are inadequately controlled by octreotide or lanreotide ( 2 ). Long-term outcomes from clinical studies have demonstrated effective and consistent biochemical control with pasireotide for up to 304

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Alexandra Kiess Department of Pediatric Cardiology, Faculty of Medicine, Heart Center Leipzig, University of Leipzig, Strümpellstraße, Leipzig, Germany
Department of Child and Adolescent Medicine, Section of Pediatric Cardiology, University Hospital Jena, Am Klinikum, Jena, Germany

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Jessica Green Alder Hey Children's NHS Foundation Trust, Pediatric Intensive Care Unit, Eaton Road Liverpool, Great Britain

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Anja Willenberg Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics (ILM), University of Leipzig, Liebigstrasse, Leipzig, Germany

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Uta Ceglarek Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics (ILM), University of Leipzig, Liebigstrasse, Leipzig, Germany

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Ingo Dähnert Department of Pediatric Cardiology, Faculty of Medicine, Heart Center Leipzig, University of Leipzig, Strümpellstraße, Leipzig, Germany

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Wieland Kiess LIFE Leipzig Research Center for Civilization Diseases, University of Leipzig, Philipp-Rosenthal-Strasse, Leipzig, Germany
Department of Women and Child Health, Hospital for Children and Adolescents and Center for Pediatric Research (CPL), University of Leipzig, Liebigstrasse, Leipzig, Germany

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Mandy Vogel LIFE Leipzig Research Center for Civilization Diseases, University of Leipzig, Philipp-Rosenthal-Strasse, Leipzig, Germany
Department of Women and Child Health, Hospital for Children and Adolescents and Center for Pediatric Research (CPL), University of Leipzig, Liebigstrasse, Leipzig, Germany

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heart disease and HF, serum IGF-1 and IGF-binding protein 3 (BP3) levels were negatively correlated with serum troponin I levels ( 6 ). As part of the prospective longitudinal population-based cohort study, ‘LIFE Child’ in Leipzig, Germany, we recently

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Djeda Belharazem Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Matthias Kirchner Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany
Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Franziska Geissler Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Peter Bugert Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Martin Spahn Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Burkhard Kneitz Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Hubertus Riedmiller Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Christian Sauer Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Stefan Küffer Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Lutz Trojan Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Christian Bolenz Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Maurice Stephan Michel Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Alexander Marx Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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Philipp Ströbel Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany
Institute of Pathology, Institute of Pathology Nordhessen, Institute of Transfusion Medicine and Immunology, Departments of Urology and Pediatric Urology, University Medical Center Mannheim, Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1–3, 68135 Mannheim, Germany

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genes known to date, the insulin-like growth factor 2 ( IGF2 ) and H19 , a gene for a noncoding RNA, are probably studied best (9) . IGF2 is of special interest, as it belongs to a small set of imprinted genes that can be studied in peripheral blood

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Rossella Cannarella Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Andrea Crafa Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Sandro La Vignera Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Rosita A Condorelli Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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Aldo E Calogero Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

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acromegalic levels of IGF-I during puberty? Journal of Clinical Endocrinology and Metabolism 2019 104 2770 – 2776 . ( https://doi.org/10.1210/jc.2018-02099 ) 2 Chandrashekar V Zaczek D Bartke A . The consequences of altered somatotropic system

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Robert Rapaport Ichan School of Medicine, New York, New York, USA

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Peter A Lee Penn State College of Medicine, Hershey, Pennsylvania, USA

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Judith L Ross Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Nemours/DuPont Hospital for Children, Wilmington, Delaware, USA

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Paul Saenger Winthrop University Hospital, Mineola, New York, USA

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Vlady Ostrow Novo Nordisk Inc., Plainsboro, New Jersey, USA

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Giuseppe Piccoli Novo Nordisk Inc., Plainsboro, New Jersey, USA

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(eg, HSDS, age, insulin-like growth factor 1 (IGF-I) SDS) on changes in HSDS in response to GH therapy over time ( 12 , 13 ). The analysis described here evaluated growth outcomes (HSDS, IGF-I SDS and BMI SDS), bone age per chronological age (BA

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Caiyan Mo Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

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Tao Tong Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

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Ying Guo Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

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Zheng Li Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

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Liyong Zhong Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

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included TSS, bromocriptine, or cabergoline for GHPA, and ATD or 131I for GD. Table 2 Cases of GHPA combined with GD in the published literature. Author Year Country Age (years)/ gender Clinical manifestations GH (ng/mL) IGF-1

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Antonella Giampietro Pituitary Unit, Department of Endocrinology, Fondazione A Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

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Sabrina Chiloiro Pituitary Unit, Department of Endocrinology, Fondazione A Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

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Claudio Urbani Endocrinology II Unit, Department of Medicine, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy

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Rosario Pivonello Dipartimento Di Medicina Clinica E Chirurgia, Sezione Di Endocrinologia, Università Federico II di Napoli, Naples, Italy

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Martin Ove Carlsson Global Medical Affairs, Pfizer Rare Disease, Brussels, Belgium

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Francesca Dassie Department of Medicine - DIMED, University of Padua, Padua, Italy

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Nunzia Prencipe Division of Endocrinology, Diabetology and Metabolism, Department of Medical Science, University of Turin, Turin, Italy

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Marta Ragonese Unit of Endocrinology, Department of Human Pathology, University of Messina, Messina, Italy

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Roy Gomez Global Medical Affairs, Pfizer Rare Disease, Brussels, Belgium

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Simona Granato Medical Department, Pfizer Italia, Rome, Italy

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Salvatore Cannavò Unit of Endocrinology, Department of Human Pathology, University of Messina, Messina, Italy

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Silvia Grottoli Division of Endocrinology, Diabetology and Metabolism, Department of Medical Science, University of Turin, Turin, Italy

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Pietro Maffei Department of Medicine - DIMED, University of Padua, Padua, Italy

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Annamaria Colao Dipartimento Di Medicina Clinica E Chirurgia, Sezione Di Endocrinologia, Università Federico II di Napoli, Naples, Italy

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Fausto Bogazzi Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

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Antonio Bianchi Pituitary Unit, Department of Endocrinology, Fondazione A Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

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nerve palsies, intracranial hypertension and rhinoliquorrhea. This investigation was based on the complete analysis set of ACROSTUDY, including data from 15 countries for a total of 2221 enrolled patients. Information on IGF-1 status (i.e. below the

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Julie M Silverstein Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8127, St Louis, Missouri 63110, USA

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2014 10 243 – 248 . ( doi:10.1038/nrendo.2014.21 ). 16 Holdaway IM Bolland MJ Gamble GD . A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly . European Journal of Endocrinology 2008 159 89

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Katherine A Bolton Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Priority Research Centre for Cancer, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia

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Kelly A Avery-Kiejda Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Priority Research Centre for Cancer, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia

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Elizabeth G Holliday Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
Clinical Research Design, IT and Statistical Support Unit, Hunter Medical Research Institute, Newcastle, New South Wales, Australia

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John Attia Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
Clinical Research Design, IT and Statistical Support Unit, Hunter Medical Research Institute, Newcastle, New South Wales, Australia

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Nikola A Bowden Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Priority Research Centre for Cancer, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia

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Rodney J Scott Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Priority Research Centre for Cancer, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
Molecular Medicine, Pathology North, John Hunter Hospital, Newcastle, New South Wales, Australia
Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, University Drive, Newcastle, New South Wales, Australia

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143 – 163 . ( doi:10.1210/edrv-16-2-143 ) 17 Laban C Bustin SA Jenkins PJ. The GH-IGF-I axis and breast cancer . Trends in Endocrinology & Metabolism 2003 14 28 – 34 . ( doi:10.1016/S1043-2760(02)00003-6 ) 18 Chen X Guan J

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Bernardo Maia Neuroendocrinology Research Center/Endocrinology Division – Medical School and Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

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Leandro Kasuki Neuroendocrinology Research Center/Endocrinology Division – Medical School and Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Neuroendocrinology Division – Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil
Endocrinology Division – Hospital Federal de Bonsucesso, Rio de Janeiro Brazil

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Mônica R Gadelha Neuroendocrinology Research Center/Endocrinology Division – Medical School and Hospital Universitário Clementino Fraga Filho – Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Neuroendocrinology Division – Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil
Neuropatology and Molecular Genetics Laboratory – Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil

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Introduction Acromegaly is a chronic systemic rare disease most commonly caused by a somatotroph pituitary adenoma with autonomous overproduction of growth hormone (GH) and a consequent increase in insulin-like growth factor type I (IGF-I

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