Brook's Clinical Pediatric Endocrinology

Charles Brook, 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.

Mehul Dattani, MD, FRCP, 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.

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 Köhler

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 Hypothalamo-Pituitary Axis 133
Hoong-Wei Gan, Kyriaki-Sandy Alatzoglou, and Mehul T. Dattani

Introduction 133

The Hypothalamo-Pituitary Neuroendocrine Axis 134

Hypothalamo-Pituitary Development 134

Congenital Disorders of Hypothalamo-Pituitary Development 144

Acquired Disorders of Hypothalamo-Pituitary 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 IGF-I Deficiency) 213

Growth Disorders not Related to the GH-IGF 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, Jean-Claude 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 Long-Term 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

Post-Neonatal 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 (APS1) 483

Autoimmune Polyendocrinopathy Syndrome Type 2 and Associated Disorders 494

Other Single Gene Disorders Associated with Immune Dysregulation and Autoimmune Endocrinopathies 499

Conclusion 502

References 502

12 Endocrine Neoplasia 507
Constantine A. Stratakis and Emmanouil Saloustros

Thyroid Neoplasia: Nodules and Cancer 507

Paragangliomas and Phaeochromocytomas 511

Adrenocortical Cancers 521

Tumours of the Ovary 524

Tumours of the Testes 528

References 530

13 Endocrine Late Effects of Cancer Treatments 533
Wassim Chemaitilly and Melissa M. Hudson

Prevalence and Risk Factors for Endocrine Late Effects 538

Diagnosis and Management of Common Endocrine Late Effects 546

Summary 550

References 550

Weblinks 552

14 Disorders of Water Balance 553
Natascia Di Iorgi, Flavia Napoli, Giovanni Morana, and Mohamad Maghnie

Regulation of Water Balance 554

Diabetes Insipidus (DI) 558

Central Diabetes Insipidus and Adipsia 572

Primary Polydipsia 572

Nephrogenic Diabetes Insipidus 573

The Syndrome of Inappropriate Antidiuretic Hormone Secretion 573

Management of Central Diabetes Insipidus 573

Treatment of Nephrogenic Diabetes Insipidus 574

Treatment of Inappropriate Antidiuretic Hormone Secretion 574

Challenges 575

Conclusions 575

Clinical Guidelines 575

References 576

15 Diabetes Mellitus 583
G.R. Ambler, F.J. Cameron, K. Joshi, and D.K. Wherrett

Type 1 Diabetes 583

Type 2 Diabetes 626

Cystic Fibrosis-Related Diabetes 637

Monogenic Forms of Diabetes 639

Rare Forms of Diabetes 647

Living with Diabetes 648

References 649

16 Disorders Associated with Hypoglycaemia in Children 671
Pratik Shah, Emma Footit, and Ritika Kapoor

Introduction 671

Physiology of Blood Glucose Control 672

Role of Gut Hormones in Glucose Homeostasis 673

Metabolic Adaptation to Birth 673

Metabolic Adaptation to Feeding and Fasting 674

The Regulation of Insulin Secretion and Role of KATP Channels 675

Definition of Hypoglycaemia 676

Aetiology and Clinical Approach to Hypoglycaemia 678

Investigations for Hypoglycaemia 680

Emergency Management of Hypoglycaemia 682

Causes of Hypoglycaemia 682

17 Obesity 701
Wieland Kiess

Introduction 701

Definitions, Differential Diagnosis, Assessments and Measurements 701

Aetiology of Obesity 703

Common or Multifactorial Obesity and Fetal Programming 705

Neurobiology of Satiety and Hunger 705

Hedonistic Signals and Addiction 706

Behaviour, Hypothalamus and Obesogenic Environment 707

Biology of Adipose Tissue and Adipocytes 707

Microbiota 708

Endocrinology of Obesity 709

Epigenetics 709

Social Inheritance 709

Sociodemographics 710

Nutrition and Malnutrition 710

Physical Activity 711

Sedentary Behaviour 711

Endocrine-Disrupting Chemicals and Toxicology 711

Media Use 712

Cultural Aspects 712

Evolution 712

Epidemiology 713

Developed Countries 713

Developing Countries 713

Co-Morbidities and Consequences 713

Social Participation 718

Mortality 719

Health Economics 720

Treatments 720

Microbiota 723

Urban Living 724

Advertising Industries 724

Conclusions 725

Further Reading 726

Weblinks 728

18 Genetic Obesity Syndromes 729
Tinh-Hai Collet and I. Sadaf Farooqi

Introduction 729

Genetic Contributors to Obesity: The Evidence 729

Genetic Obesity Syndromes: An Overview 730

Obesity with Developmental Delay 730

Obesity without Development Delay 732

Conclusions 734

References 734

Weblinks 736

19 Endocrine Care During Adolescence into Young Adulthood 737
Helena Gleeson

Introduction 737

Adolescence and Young Adulthood 737

Exploratory and Health-Related Behaviours 740

Addressing Adherence 743

Young People with Endocrine Conditions 744

Conclusion 750

References 751

Index 757