Disorders of Growth Hormone in Childhood

Philip G. Murray; Peter E. Clayton

Disorders of Growth Hormone in Childhood

Review

In: Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.

2022 Mar 9.

Authors

Philip G. Murray¹, Peter E. Clayton²

Book Editors

Kenneth R Feingold¹, S. Faisal Ahmed², Bradley Anawalt³, Marc R Blackman⁴, Alison Boyce⁵, George Chrousos⁶, Emiliano Corpas⁷, Wouter W de Herder⁸, Ketan Dhatariya⁹, Kathleen Dungan¹⁰, Johannes Hofland¹¹, Sanjay Kalra¹², Gregory Kaltsas¹³, Nitin Kapoor¹⁴, Christian Koch¹⁵, Peter Kopp¹⁶, Márta Korbonits¹⁷, Christopher S Kovacs¹⁸, Wendy Kuohung¹⁹, Blandine Laferrère²⁰, Miles Levy²¹, Elizabeth A McGee²², Robert McLachlan²³, Radhika Muzumdar²⁴, Jonathan Purnell²⁵, Rodolfo Rey²⁶, Rakesh Sahay²⁷, Amy S Shah²⁸, Frederick Singer²⁹, Mark A Sperling³⁰, Constantine A Stratakis³¹, Dace L Trence³², Don P Wilson³³

Affiliations

¹ Division of Developmental Biology and Medicine, School of Medical Sciences University of Manchester and Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Oxford Road, Manchester, UK, M13 9WL.
² Division of Developmental Biology and Medicine, School of Medical Sciences, University of Manchester and Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Oxford Road, Manchester, UK, M13 9WL.

Book Affiliations

¹ Professor of Medicine Emeritus, University of California, San Francisco, CA
² Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK
³ Chief of Medicine at the University of Washington Medical Center and Professor and Vice Chair of the Department of Medicine, University of Washington
⁴ Sr. Physician Scientist, Washington DC VA Medical Center; Professor of Medicine & Rehabilitation Medicine, Georgetown University; Clinical Professor of Medicine, Biochemistry and Molecular Medicine, George Washington University; and Professor of Medicine (Part-time), Johns Hopkins University
⁵ Pediatric Endocrinologist and Associate Research Physician in the Skeletal Diseases and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health
⁶ Professor of Pediatrics and Endocrinology, Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, Greece
⁷ M.D. Ph.D in Gerontology. Honorary Professor of Medicine, Universidad de Alcalá, Madrid. Consultant in Endocrinology, Hospital HLA Guadalajara (Spain).
⁸ Professor of Endocrine Oncology, Erasmus MC and Erasmus MC Cancer Center, Rotterdam, the Netherlands
⁹ Consultant in Diabetes, Endocrinology and General Medicine, Norfolk and Norwich University Hospitals NHS Foundation Trust and University of East Anglia, Norwich, UK.
¹⁰ Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Ohio State University
¹¹ Consultant Endocrinologist, Erasmus MC and Erasmus MC Cancer Center, Rotterdam, the Netherlands
¹² Consultant Endocrinologist, Department of Endocrinology, Bharti Hospital, Karnal, India
¹³ Professor of General Medicine-Endocrinology, 1st Department of Propaedeutic Medicine, National and Kapodistrian University of Athens, Athens, Greece
¹⁴ Professor of Endocrinology, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College & Hospital, Vellore, Tamil Nadu, India, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Australia.
¹⁵ Professor, The University of Tennessee Health Science Center, Memphis, Tennessee
¹⁶ Professor of Medicine and Chief of the Division of Endocrinology, Diabetology and Metabolism, University of Lausanne, Switzerland
¹⁷ Professor of Endocrinology and Metabolism, Centre Lead for Endocrinology and Deputy Institute Director, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, England
¹⁸ University Research Professor and Professor of Medicine (Endocrinology and Metabolism), Obstetrics & Gynecology, and BioMedical Sciences, at Memorial University of Newfoundland in St. John’s, Newfoundland, Canada.
¹⁹ Director of the Division of Reproductive Endocrinology at Boston Medical Center and an Associate Professor of Obstetrics and Gynecology at the Boston University School of Medicine
²⁰ Professor of Medicine, New York Nutrition Obesity Research Center, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
²¹ Consultant endocrinologist at University Hospitals of Leicester and Honorary Associate Professor at Leicester University
²² Professor of Obstetrics and Gynecology at the University of Vermont and Director of the Division of Reproductive Endocrinology and Infertility. Burlington, Vermont
²³ Director of Clinical Research, Hudson Institute of Medical Research; Consultant Endocrinologist, Monash Medical Centre, Melbourne, Australia
²⁴ Allan L. Drash Endowed Chair, Chief, Division of Endocrinology and Diabetes, UPMC Children’s Hospital of Pittsburgh, Professor of Pediatrics and Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA
²⁵ Professor of Medicine, Knight Cardiovascular Institute and the Division of Endocrinology, and Associate Director, Bob and Charlee Moore Institute for Nutrition and Wellness, Oregon Health and Science University, Portland, OR
²⁶ Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, C1425EFD Buenos Aires; and Departamento de Histología, Biología Celular, Embriología y Genética, Facultad de Medicina, Universidad de Buenos Aires, C1121ABG Buenos Aires, Argentina
²⁷ Professor and Head of Department of Endocrinology, Osmania Medical College and Osmania General Hospital, Hyderabad, India.
²⁸ Professor of Pediatrics, The University of Cincinnati, Department of Pediatrics and Cincinnati Children’s Hospital Medical Center, Division of Endocrinology, Cincinnati, OH, USA
²⁹ Director of the Endocrine/Bone Disease Program, Saint Johns Cancer Institute at Saint John’s Health Center, Santa Monica, CA; Clinical Professor of Medicine, UCLA School of Medicine, Los Angeles, CA
³⁰ Professorial Lecturer, Division of Pediatric Endocrinology and Diabetes, Icahn School of Medicine at Mount Sinai, New York, NY. Emeritus Professor and Chair, Department of Pediatrics, University of Pittsburgh.
³¹ CSO, ELPEN, Inc. & Director, Research Institute, Athens, Greece & Senior Investigator, Human Genetics & Precision Medicine, FORTH (ITE), Heraklion, Greece. Emeritus Scientific Director & Senior Investigator, NICHD, NIH, Bethesda, MD, USA
³² Professor of Medicine, Emeritus, University of Washington, Seattle, WA
³³ Endowed Chair, Cardiovascular Health and Risk Prevention, Pediatric Endocrinology and Diabetes, Cook Children's Medical Center, Fort Worth, TX

PMID: 25905205
Bookshelf ID: NBK278971

Excerpt

Growth is a fundamental process of childhood and growth disorders remain one of the commonest reasons for referral to a pediatric endocrinologist. Growth can be divided into four phases – fetal, infancy, childhood and the pubertal phase with different hormonal components influencing growth at each stage. The GH-IGF1 axis plays a major role in the childhood phase of growth with a significant role alongside sex steroids during puberty while in infancy thyroid hormone and nutrition are vital. Although an uncommon cause of short stature disorders of the GH-IGF1 axis are extremely important due to the effectiveness of recombinant human growth hormone therapy for the child with GH deficiency (GHD). Here we review the diagnosis of growth hormone deficiency through a combination of auxology, biochemistry, imaging, and genetic testing. Particular focus is given to the accuracy of IGF-1/BP3 for diagnosis as well as the known problems with GH stimulation tests and GH assays. Isolated GHD is caused by mutations in GH1, BTK, and RNPC3 while GHD seen as part of multiple pituitary hormone deficiency is known to be caused by mutations in a wide variety of genes. A variety of structural malformations of the brain can be associated with congenital GHD with the commonest being the presence of an ectopic posterior pituitary or Septo-optic dysplasia. Acquired GHD is rarer and caused by tumors, radiotherapy, hypophysitis, and traumatic brain injury. Treatment with recombinant human GH is highly efficacious in improving height in children with GH deficiency and extremely safe. Short stature disorders are, rarely, also caused by a variety of other disorders of the GH-IGF1 axis. Resistance to growth hormone is seen in Laron syndrome and in mutations in IGF1 and IGF1R while decreased bioavailability of IGF1 is seen in ALS deficiency and PAPPA2 deficiency. Treatment with recombinant human IGF1 (rhIGF1) is available for those with IGF-I deficiency caused by either Laron syndrome or IGF1 mutations. rhIGF1 is effective in improving height but treatment is less effective than the use of GH to treat GH deficiency. The role of IGF1 in pre-natal growth is highlighted by the phenotype of patients with IGF1R or IGF1 mutations where pre-natal growth is commonly impaired and children born small for gestational age. GH excess is much rarer than GH deficiency in childhood and can be caused by pituitary adenomas, optic nerve gliomas (seen predominantly with NF1), McCune Albright syndrome, or Carney complex. Treatment is with surgery, somatostatin analogs, or GH receptor antagonists. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

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