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      Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective

      guideline
      a , * , b , c , d , e , f , g , h , i , j , k , l , m , n , o , p , q , r , s , t , u , v , w , x , y , z , A , B , C , D , E , F , G , H , I , J , K
      Hormone Research in Paediatrics
      S. Karger AG
      Growth, Pediatrics, Guideline, Growth hormone, Treatment

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          Abstract

          The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.

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          Most cited references76

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          Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop.

          Our objective was to summarize important advances in the management of children with idiopathic short stature (ISS). Participants were 32 invited leaders in the field. Evidence was obtained by extensive literature review and from clinical experience. Participants reviewed discussion summaries, voted, and reached a majority decision on each document section. ISS is defined auxologically by a height below -2 sd score (SDS) without findings of disease as evident by a complete evaluation by a pediatric endocrinologist including stimulated GH levels. Magnetic resonance imaging is not necessary in patients with ISS. ISS may be a risk factor for psychosocial problems, but true psychopathology is rare. In the United States and seven other countries, the regulatory authorities approved GH treatment (at doses up to 53 microg/kg.d) for children shorter than -2.25 SDS, whereas in other countries, lower cutoffs are proposed. Aromatase inhibition increases predicted adult height in males with ISS, but adult-height data are not available. Psychological counseling is worthwhile to consider instead of or as an adjunct to hormone treatment. The predicted height may be inaccurate and is not an absolute criterion for GH treatment decisions. The shorter the child, the more consideration should be given to GH. Successful first-year response to GH treatment includes an increase in height SDS of more than 0.3-0.5. The mean increase in adult height in children with ISS attributable to GH therapy (average duration of 4-7 yr) is 3.5-7.5 cm. Responses are highly variable. IGF-I levels may be helpful in assessing compliance and GH sensitivity; levels that are consistently elevated (>2.5 SDS) should prompt consideration of GH dose reduction. GH therapy for children with ISS has a similar safety profile to other GH indications.
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            Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency

            Background/Aims: On behalf of the Drug and Therapeutics, and Ethics Committees of the Pediatric Endocrine Society, we sought to update the guidelines published in 2003 on the use of growth hormone (GH). Because idiopathic short stature (ISS) remains a controversial indication, and diagnostic challenges often blur the distinction between ISS, GH deficiency (GHD), and primary IGF-I deficiency (PIGFD), we focused on these three diagnoses, thereby adding recombinant IGF-I therapy to the GH guidelines for the first time. Methods: This guideline was developed following the GRADE approach (Grading of Recommendations, Assessment, Development, and Evaluation). Results: This guideline provides recommendations for the clinical management of children and adolescents with growth failure from GHD, ISS, or PIGFD using the best available evidence. Conclusion: The taskforce suggests that the recommendations be applied in clinical practice with consideration of the evolving literature and the risks and benefits to each individual patient. In many instances, careful review highlights areas that need further research.
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              Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society.

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                Author and article information

                Journal
                HRP
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2019
                December 2019
                12 September 2019
                : 92
                : 1
                : 1-14
                Affiliations
                [_a] aDisciplina de Endocrinologia, Departamento de Medicina Interna, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
                [_A] ADepartment of Pediatrics, Tongji Hospital, Tongji Medical Colleage, Huazhong University of Science and Technology, Wuhan, China
                [_b] bInstitute of Endocrinology and Diabetes, The University of Sydney, Sydney, New South Wales, Australia
                [_B] BDivision of Endocrinology, Department of Pediatrics, University of Minnesota Masonic Children’s Hospital, Minneapolis, Minnesota, USA
                [_c] cDivision of Endocrinology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
                [_C] CDivision of Pediatric Endocrinology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
                [_d] dEndocrine Laboratory, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
                [_D] DExplorations Fonctionnelles Endocriniennes, AP-HP Hôpital Trousseau, Centre de Recherche Saint Antoine, INSERM, Sorbonne Université, Paris, France
                [_e] eNeuroendocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
                [_E] EDepartment of Pediatrics, Robert Wood Johnson Medical School, Child Health Institute of New Jersey-Rutgers University, New Brunswick, New Jersey, USA
                [_f] fDepartment of Pediatrics, Federal University of Parana, Curitiba, Brazil
                [_F] FUniversity Children´s Hospital, Tübingen, Germany
                [_g] gPaediatric Endocrinology, Genetics, and Metabolism, Virtus Medical Group and The University of Hong Kong, Hong Kong SAR, China
                [_G] GDepartment of Pediatrics, University of Virginia, Charlottesville, Virginia, USA
                [_h] hDepartment of Endocrinology, Perth Children’s Hospital, Child and Adolescent Health Service, Perth, Washington, Australia
                [_H] HOregon Health and Science University, Portland, Oregon, USA
                [_i] iDivision of Paediatrics, School of Medicine, University of Western Australia, Perth, Washington, Australia
                [_I] INYU Winthrop Hospital, Mineola, New York, USA
                [_j] jThe Centre for Child Health Research, Telethon Kids Institute, University of Western Australia, Perth, Washington, Australia
                [_J] JDepartment of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
                [_k] kDivision of Endocrinology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
                [_K] KPediatric Endocrinology Division, Children’s Hospital, University of Bonn, Bonn, Germany
                [_l] lLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA
                [_m] mDivision of Endocrinology, Children’s National Health System, Washington, District of Columbia, USA
                [_n] nEndocrine and Diabetes Service, CHU Sainte-Justine and University of Montreal, Montreal, Québec, Canada
                [_o] oEndocrinology, Genetics, and Metabolism, Beijing Diabetes Center for Children and Adolescents, Medical Genetics Department, Beijing Children’s Hospital, Beijing, China
                [_p] pDivision of Endocrinology and Metabolism, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan
                [_q] qDepartment of Medicine, Stanford University School of Medicine and VA Palo Alto Health Care System, Palo Alto, California, USA
                [_r] rLiggins Institute, University of Auckland, Auckland, New Zealand
                [_s] sDivision of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo, Japan
                [_t] tUnidade de Endocrinologia Genética (LIM25), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
                [_u] uDepartment of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
                [_v] vService d’Endocrinologie et des Maladies de la Reproduction, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, Paris, France
                [_w] wHirabai Cowasji Jehangir Medical Research Institute (HCJMRI), Jehangir Hospital, Pune, India
                [_x] xEdison Biotechnology Institute and Department of Biomedical Sciences, HCOM Ohio University Athens, Athens, Ohio, USA
                [_y] yInstitute of Clinical Science, Pediatrics, Umeå University, Umeå, Sweden
                [_z] zUnidade de Endocrinologia Pediátrica, Area da Mulher, Criança e Adolescente, Centro Hospitalar Universitário de Lisboa Central-Hospital de Dona Estefânia, Lisbon, Portugal
                Author notes
                *Paulo Ferrez Collett-Solberg, MD, PhD, Pavilhão Reitor Haroldo Lisboa da Cunha, térreo, Rua São Francisco Xavier 524, Maracanã, Rio de Janeiro 20550-013 (Brazil), E-Mail paulosolberg@yahoo.com
                Author information
                https://orcid.org/0000-0003-2567-7360
                https://orcid.org/0000-0002-9405-2981
                https://orcid.org/0000-0002-7526-3142
                Article
                502231 PMC6979443 Horm Res Paediatr 2019;92:1–14
                10.1159/000502231
                PMC6979443
                31514194
                9a2012e8-3d48-4192-b147-2421d1d164c9
                © 2019 The Author(s)Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 04 June 2019
                : 18 July 2019
                Page count
                Tables: 2, Pages: 14
                Categories
                Guidelines

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Growth,Pediatrics,Treatment,Guideline,Growth hormone

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