Brook's Clinical Pediatric Endocrinology

MEHUL T. DATTANI, MD, FRCP, FRCPCH, is Professor of Pediatric Endocrinology at the UCL GOS Institute of Child Health and Head of Pediatric Endocrinology at Great Ormond Street Hospital for Children, University College London Hospitals, and Institute of Child Health. He is currently the Chair of the Programme Organising Committee of the European Society for Paediatric Endocrinology. CHARLES G.D. BROOK, MA, MD, FRCP, was the first Professor of Pediatric Endocrinology in the UK and the founder of the London Centre for Pediatric Endocrinology at Great Ormond Street Hospital and University College London Hospitals. He was the recipient of the Andrea Prader Prize in 2000, the most prestigious award for outstanding leadership and research in the gift of the European Society for Paediatric Endocrinology.

List of Contributors xix Preface xxiii About the Companion Website xxv 1 Genetics and Genomics 1 Anu Bashamboo and Ken McElreavey Introduction 1 Basic Concepts in Human Genetics and Genomics 1 Classes of RNA Molecules and their Functions 4 Gene Mutations and Inheritance 7 Human Populations and Genetic Variation 12 Epigenetics 14 Advances in Genomic Analysis 15 Establishing Variant Causality 19 The Age of Precision Medicine 24 Clinical Guidelines 24 Acknowledgments 25 Glossary of Terms 25 Further Reading 29 2 Measuring Hormones 31 Gerhard Binder Introduction 31 Hormone Assays 31 Assay Validity 33 Technical Pitfalls When Measuring Hormones 36 Clinical Assay Validity 38 Stimulation Tests, Suppression Tests and Profiles 42 Optimal Clinical Use of Hormone Tests 44 Acknowledgements 44 References 44 3 Fetal Endocrinology 47 Harshini Katugampola, Evelien F. Gevers, and Mehul T. Dattani Introduction 48 Transplacental Passage of Hormones 48 Development of Fetal Endocrine Systems 50 Neutralization of Hormone Activity in the Fetus 82 Plasticity of Fetal Endocrine Systems 84 Fetal Adaptations for Transition to Extrauterine Life 85 Frontiers in Fetal and Neonatal Endocrinology 89 References 90 4 Disorders of Sex Development 105 Martine Cools and Birgit Khler Normal Sex Development 105 Terminology 106 Causes of DSD 107 Impaired Gonadal Development 108 Disturbances of Testicular Hormone Production or Action 113 Virilization of an XX Individual 116 Management of DSD 118 Clinical Management 122 Other Examples of XY DSD 126 Future Perspectives 127 References 127 Weblinks 131 5 Disorders of HypothalamoPituitary Axis 133 HoongWei Gan, KyriakiSandy Alatzoglou, and Mehul T. Dattani Introduction 133 The HypothalamoPituitary Neuroendocrine Axis 134 HypothalamoPituitary Development 134 Congenital Disorders of HypothalamoPituitary Development 144 Acquired Disorders of HypothalamoPituitary Dysfunction 155 Investigation of Hypopituitarism 172 Management of Hypopituitarism 173 Conclusion 174 References 174 6 Disorders of Growth 199 P.G. Murray and P.E. Clayton Normal Growth 200 Short Stature 205 Acquired GH Deficiency 211 Disorders of GH Action and GH Sensitivity (Primary IGFI Deficiency) 213 Growth Disorders not Related to the GHIGF Axis 216 Syndromes Associated with Short Stature 219 Idiopathic Short Stature 225 Skeletal Dysplasias 227 Tall Stature 229 References 233 7 Puberty and Its Disorders 235 Sasha R. Howard, Nicolas de Roux, Juliane Leger, JeanClaude Carel, and Leo Dunkel Normal Puberty 235 Precocious Puberty 256 Delayed Puberty 265 Conclusions 283 References 284 8 The Thyroid Gland 289 Catherine Peters and Nadia Schoenmakers Section 1: Development of the Thyroid Axis 289 Section 2: Clinical Thyroid Disorders 301 Section 3: Diagnostic Pitfalls 315 References 320 Weblinks 334 9 The Adrenal Cortex and Its Disorders 335 Claire R. Hughes, Elim Man, and John C. Achermann Introduction 335 Development, Function and Regulation of the Adrenal Gland 336 Adrenal Insufficiency (AI) 353 Adrenal Excess 393 Education, Support and LongTerm Care 401 10 The Parathyroid and Disorders of Calcium and Bone Metabolism 409 Jeremy Allgrove and Moira Cheung Introduction 409 Physiology of Calcium and Bone Metabolism 409 Physiology of Bone Metabolism 421 Interactions between Calciotropic Agents 425 Fetal and Neonatal Calcium Metabolism 425 PostNeonatal Calcium, Phosphate and Magnesium Metabolism and the Calcium Cascade 426 Clinical Conditions 426 Drugs Used in the Treatment of Disorders of Calcium and Bone Metabolism 467 Summary 470 References 472 Weblinks 479 11 Polyglandular Autoimmune Syndromes 481 Catherine J. Owen, Mario Abinun, Simon H.S. Pearce, and Tim D. Cheetham Introduction 481 Autoimmune Polyendocrinopathy Syndrome Type 1 (AP