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Abstract
In a single, convenient volume, Pediatric Endocrinology offers complete coverage of all aspects of basic science and clinical practice, ideal for both pediatricians and endocrinologists. Pediatric endocrinology expert Dr. Mark Sperling teams up with world-renowned authors to bring you up to date with the latest key developments in every area of the field, providing invaluable guidance on how your clinical decision making will be affected by today’s technological and scientific advances.
- Consult this title on your favorite e-reader , conduct rapid searches, and adjust font sizes for optimal readability.
- Determine the best possible course for every patient with easy-to-follow algorithms in every clinical chapter.
- Stay up to date with today’s hottest topics , including neonatal diabetes mellitus, Type II childhood diabetes, molecular endocrinology, and genetics.
- Explore the impact of today’s advances and challenges, including explosive growth in molecular biology, sophisticated imaging techniques, and an increase in both pediatric diabetes and obesity.
- Quickly access the information you need with a new, streamlined organization (Concepts, Endocrine Disorders of the Newborn, Endocrine Disorders of Childhood and Adolescence, and Laboratory Tests and Imaging).
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front cover | Cover | ||
| Inside front cover | 1 | ||
| Front matter | i | ||
| Pediatric endocrinology | i | ||
| Copyright | ii | ||
| Dedication | iii | ||
| Foreword to the first edition | v | ||
| Preface | vii | ||
| Acknowledgments | ix | ||
| Contributors | xi | ||
| Table of contents | xv | ||
| I Principles and methods of pediatric endocrinology | 1 | ||
| 1 Overview and principles of pediatric endocrinology | 1 | ||
| Historical background | 2 | ||
| Impact of hormonal assays and molecular biology | 3 | ||
| Unique aspects of pediatric endocrinology | 5 | ||
| Fetal origins of adult disease | 5 | ||
| Acquisition of patterns of hormone secretion and action | 5 | ||
| Adaptations in endocrine function at birth | 6 | ||
| Maintenance of body temperature | 6 | ||
| Glucose homeostasis | 6 | ||
| Gonadotropins and sex hormones | 6 | ||
| Evaluating endocrine disorders in infancy and childhood | 7 | ||
| Concluding remarks | 7 | ||
| References | 7 | ||
| 2 Molecular endocrinology and endocrine genetics | 9 | ||
| Introduction | 9 | ||
| Basic molecular tools | 9 | ||
| Isolation and digestion of DNA and southern blotting | 9 | ||
| Restriction fragment length polymorphism and other polymorphic DNA studies | 11 | ||
| Polymerase chain reaction | 11 | ||
| RNA analysis | 11 | ||
| Microrna | 16 | ||
| Detection of mutations in genes | 16 | ||
| Direct methods | 16 | ||
| Indirect methods | 18 | ||
| Positional genetics in endocrinology | 21 | ||
| The principles of positional genetics | 21 | ||
| Genomic identification of “endocrine” genes | 22 | ||
| Impact of modern sequencing in clinical practice | 23 | ||
| Expression studies (microarrays, sage) | 24 | ||
| Chromosome analysis and molecular cytogenetics | 25 | ||
| Outline of methods | 25 | ||
| Applications | 25 | ||
| Future developments | 26 | ||
| Molecular basis of pediatric endocrinopathies | 26 | ||
| Defects in peptide hormones | 27 | ||
| Genomic deletions causing human endocrine disease | 27 | ||
| Point mutations | 27 | ||
| Defects in peptide hormone receptors | 28 | ||
| Insulin receptor | 28 | ||
| Gh receptor | 29 | ||
| Principles of interpretation of genetic tests in the diagnosis and management of pediatric endocrine diseases | 29 | ||
| Recombinant DNA technology and therapy of pediatric endocrine diseases | 30 | ||
| Concluding remarks | 31 | ||
| References | 31 | ||
| 3 Receptor Transduction Pathways Mediating Hormone Action | 34 | ||
| INTRODUCTION | 34 | ||
| G PROTEIN–COUPLED RECEPTORS | 35 | ||
| CLASS A RECEPTORS THAT TRANSDUCE HORMONE ACTION | 41 | ||
| The Peptide Receptor Group | 41 | ||
| Adrenocorticotropin and Melanocortin-2 Receptors | 41 | ||
| Other Melanocortin Receptors | 41 | ||
| Vasopressin Receptors | 42 | ||
| The Glycoprotein Hormone Receptor Group | 43 | ||
| LHCGR Receptors | 43 | ||
| FSH Receptors | 44 | ||
| TSH Receptors | 45 | ||
| HCG and TSH Receptors during Pregnancy | 46 | ||
| The Gonadotropin-Releasing Hormone Receptor Group | 46 | ||
| Gonadotropin-Releasing Hormone Receptors | 46 | ||
| The Thyrotropin-Releasing Hormone and Secretagogue Receptor Group | 47 | ||
| Thyrotropin-Releasing Hormone Receptors | 47 | ||
| Other Class A Receptors That Transduce Hormone Action | 47 | ||
| Free Fatty Acid Receptor 1 | 47 | ||
| KISS1 Receptor/GPR54 | 48 | ||
| Orexin Receptors | 48 | ||
| Ghrelin Receptors | 48 | ||
| Melanin-Concentrating Hormone Receptors | 49 | ||
| CLASS B RECEPTORS THAT TRANSDUCE HORMONE ACTION | 49 | ||
| Growth Hormone–Releasing Hormone Receptor | 49 | ||
| Gastric Inhibitory Polypeptide Receptors | 50 | ||
| Parathyroid Hormone and Parathyroid Hormone–Related Peptide Receptors | 50 | ||
| Other Class B Receptors That Transduce Hormone Action | 51 | ||
| CLASS C RECEPTORS THAT TRANSDUCE HORMONE ACTION | 51 | ||
| Calcium-Sensing Receptors | 51 | ||
| G PROTEIN GENE DISORDERS | 52 | ||
| Inactivating Mutations of the GNAS Gene | 52 | ||
| Activating Mutations of the GNAS Gene | 53 | ||
| CYTOKINE RECEPTORS | 53 | ||
| Structure and Function of Type 1 Cytokine Receptors | 54 | ||
| Cytokine Receptors That Transduce Hormone Action | 54 | ||
| Growth Hormone Receptors | 54 | ||
| LEPTIN RECEPTORS | 55 | ||
| RECEPTOR TYROSINE KINASES | 56 | ||
| Insulin Receptor Tyrosine Kinase Family | 56 | ||
| THE INSULIN RECEPTOR | 58 | ||
| THE INSULIN-LIKE GROWTH FACTOR-1 RECEPTOR | 58 | ||
| THE FIBROBLAST GROWTH FACTOR RECEPTOR FAMILY | 59 | ||
| Fibroblast Growth Factor Receptor 1 | 59 | ||
| Fibroblast Growth Factor Receptors 2-4 | 60 | ||
| NUCLEAR RECEPTORS | 60 | ||
| General Structure of the Nuclear Receptors | 60 | ||
| SUBFAMILY 1 NUCLEAR RECEPTORS: THYROID HORMONE, VITAMIN D3, AND PEROXISOME PROLIFERATOR–ACTIVATED RECEPTORS | 64 | ||
| Thyroid Hormone Receptors | 64 | ||
| Vitamin D Receptor | 64 | ||
| PPARγ | 64 | ||
| SUBFAMILY 2 NUCLEAR RECEPTORS: HEPATOCYTE NUCLEAR FACTOR AND RETINOID X RECEPTORS | 65 | ||
| HNF Receptors | 65 | ||
| SUBFAMILY 3 NUCLEAR RECEPTORS: THE STEROID RECEPTORS AND GLUCOCORTICOID, ANDROGEN, ESTROGEN, AND MINERALOCORTICOID RECEPTORS | 65 | ||
| Glucocorticoid Receptors | 65 | ||
| Androgen Receptors | 65 | ||
| Estrogen Receptors | 66 | ||
| Mineralocorticoid Receptors | 67 | ||
| SUBFAMILY 0 NUCLEAR RECEPTORS: DAX1 | 67 | ||
| DAX1 | 67 | ||
| Summary | 68 | ||
| References | 68 | ||
| 4 Laboratory methods in pediatric endocrinology | 90 | ||
| Introduction | 90 | ||
| Hormonal assays | 91 | ||
| Immunoassays | 91 | ||
| Competitive immunoassay versus immunometric (sandwich) assay | 92 | ||
| Potential confounders in immunoassays | 93 | ||
| Limitations of immunoassays | 95 | ||
| Free and bioavailable hormone tests | 95 | ||
| Mass spectrometry | 97 | ||
| Interpretation of test results | 99 | ||
| Preanalytic variables | 99 | ||
| Analytic validation, quality assurance, and quality control | 100 | ||
| Linearity/reportable range | 100 | ||
| Precision | 101 | ||
| Analytic sensitivity | 101 | ||
| Analytic specificity, interferences, and recovery | 101 | ||
| Accuracy/method comparison | 102 | ||
| Sample types and matrix effects | 102 | ||
| Stability | 102 | ||
| Carryover | 102 | ||
| Clinical validation | 102 | ||
| Summary | 106 | ||
| References | 106 | ||
| II Endocrine Disorders In the neonate | 107 | ||
| 5 Ambiguous genitalia | 107 | ||
| Introduction | 109 | ||
| Talking with the parents | 109 | ||
| Terminology | 110 | ||
| Sex determination | 111 | ||
| Development of the reproductive system | 112 | ||
| Urogenital development | 112 | ||
| Germ cell development | 113 | ||
| Human testicular development | 113 | ||
| Human ovary development | 114 | ||
| Development of internal genital structures | 115 | ||
| Development of external genital structures | 115 | ||
| Anogenital distance | 116 | ||
| Sexual differentiation of the brain | 116 | ||
| Mouse models | 116 | ||
| Disorders of gonadal differentiation | 119 | ||
| Wilms tumor gene | 119 | ||
| Wnt4 gene | 120 | ||
| Sf1/nr5a1 gene | 120 | ||
| Chromobox homolog 2 (cbx2) | 120 | ||
| 46,xy disorders of sex development (gonadal dysgenesis) | 121 | ||
| Sry | 121 | ||
| Sox9 | 121 | ||
| Dax1 | 122 | ||
| Desert hedgehog | 122 | ||
| Gata4 | 122 | ||
| Fog2 | 123 | ||
| Map3k1 | 123 | ||
| Chromosome 9p monosomy | 123 | ||
| Atr-x syndrome | 123 | ||
| Vanishing testes | 123 | ||
| Multiple congenital anomalies | 123 | ||
| Cdkn1c | 123 | ||
| Gli3 | 124 | ||
| Arx | 124 | ||
| Kat6b | 124 | ||
| Chd7 | 124 | ||
| Ovotesticular disorder of sex development | 124 | ||
| 46,xx testicular disorder of sex development | 124 | ||
| Rspo1 | 125 | ||
| XX disorder of sex development/premature ovarian failure | 125 | ||
| Foxl2 | 125 | ||
| Nobox | 125 | ||
| Figla | 125 | ||
| Disorders of cholesterol and steroid biosynthesis (also discussed in chapter 13) | 126 | ||
| Luteinizing hormone choriogonadotropin receptor gene | 127 | ||
| Smith-lemli-opitz syndrome | 127 | ||
| Congenital lipoid adrenal hyperplasia | 128 | ||
| Side chain cleavage cytochrome p450 enzyme | 128 | ||
| Virilizing congenital adrenal hyperplasias | 128 | ||
| 21-hydroxylase deficiency | 128 | ||
| 11β-hydroxylase deficiency | 130 | ||
| 3β-hydroxysteroid dehydrogenase deficiency | 130 | ||
| Defects in sex steroid biosynthesis | 130 | ||
| 17α-hydroxylase/17,20-lyase deficiency | 130 | ||
| Cytochrome B5 deficiency | 131 | ||
| 3α-hydroxysteroid dehydrogenase isozyme deficiencies | 131 | ||
| Cytochrome p450 oxidoreductase deficiency | 131 | ||
| 17β-hydroxysteroid dehydrogenase deficiency | 131 | ||
| 5α-reductase deficiency | 132 | ||
| Placental aromatase deficiency | 132 | ||
| Maternal hyperandrogenism | 132 | ||
| Disorders of androgen action | 132 | ||
| Mullerian duct abnormalities | 134 | ||
| Persistent mullerian duct syndrome | 134 | ||
| Mullerian duct abnormalties in 46,xx individuals | 134 | ||
| Hoxa genes | 134 | ||
| Microphallus, hypospadias, and cryptorchidism | 134 | ||
| Hypospadias | 134 | ||
| Cryptorchidism | 134 | ||
| Hypogonadotropic hypogonadism | 136 | ||
| Robinow syndrome | 136 | ||
| Warburg-micro syndrome | 136 | ||
| Mamld1 | 136 | ||
| Environmental disruptors | 137 | ||
| Other disorders | 137 | ||
| Exstrophy of bladder | 137 | ||
| Diagnosis | 137 | ||
| History | 137 | ||
| Physical examination | 137 | ||
| Laboratory studies | 139 | ||
| Treatment | 140 | ||
| Sex of rearing | 141 | ||
| Medical treatment | 142 | ||
| Considerations with regard to surgery | 143 | ||
| Risks for gonadal tumors | 144 | ||
| Transition from pediatrics to adult care | 145 | ||
| Psychological and genetic counseling and support and ethical considerations | 145 | ||
| Conclusions | 145 | ||
| References | 147 | ||
| 6 Hypoglycemia in the newborn and infant | 157 | ||
| Introduction | 157 | ||
| Principles of glucose metabolism | 157 | ||
| Physiology of perinatal glucose homeostasis | 159 | ||
| Glucose metabolism in the fetus | 159 | ||
| Changes at birth: Transition phase | 159 | ||
| Abnormalities of transition | 160 | ||
| Management of hypoglycemia in the first 24 hours | 160 | ||
| Hormonal and metabolic systems of fasting adaptation | 161 | ||
| Definition of hypoglycemia in neonates and infants | 163 | ||
| Clinical symptoms and signs associated with hypoglycemia | 166 | ||
| Diagnostic approach | 166 | ||
| Classification of causes of persistent hypoglycemia in the neonate and infant (box 6-2) | 167 | ||
| Disorders of insulin excess or actions | 167 | ||
| Hyperinsulinemic hypoglycemia | 168 | ||
| Transient hyperinsulinism resulting from maternal factors | 168 | ||
| Prolonged neonatal hyperinsulinism: Perinatal stress-induced hyperinsulinism | 168 | ||
| Hyperinsulinism in beckwith-wiedemann syndrome | 169 | ||
| Monogenic hyperinsulinism | 169 | ||
| Katp hyperinsulinism. | 171 | ||
| Focal katp-hyperinsulinism (focal adenomatosis). | 172 | ||
| Glutamate dehydrogenase-hyperinsulinism: The hyperinsulinism hyperammonemia syndrome (HI/HA). | 173 | ||
| SCHAD-hyperinsulinism. | 174 | ||
| Glucokinase-hyperinsulinism. | 174 | ||
| Uncoupling protein-2 hyperinsulinism. | 175 | ||
| Hepatocyte nuclear factors and hyperinsulinism: HNF1alpha and HNF4alpha-hyperinsulinism. | 175 | ||
| Hypoglycemia due to activating mutations in AKT2 | 175 | ||
| Acquired postprandial hyperinsulinemic hypoglycemia after fundoplication | 175 | ||
| Defects in counter-regulatory response | 176 | ||
| Defects in glycogenolysis and gluconeogenesis | 177 | ||
| Glucose 6-phosphatase deficiency (GSD type 1) | 177 | ||
| Disorders of fatty acid oxidation: Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD) | 178 | ||
| Defects of glucose transporters | 179 | ||
| GLUT1 deficiency | 179 | ||
| GLUT2 deficiency | 180 | ||
| Treatment | 180 | ||
| Conclusions | 181 | ||
| References | 181 | ||
| 7 Disorders of the thyroid in the newborn and infant | 186 | ||
| Introduction | 186 | ||
| Embryology, physiology, and physiopathology | 186 | ||
| Development of the thyrotropic axis | 186 | ||
| Placental transfer of iodine, T4, TRH, antithyroid drugs, and immunoglobulins | 187 | ||
| Maturation of thyroid hormone synthesis and secretion | 188 | ||
| Maturation of thyroid hormone metabolism and transport | 190 | ||
| Extrauterine thyroid adaptation | 191 | ||
| Thyroid hormone actions | 191 | ||
| Congenital hypothyroidism | 193 | ||
| Newborn screening | 193 | ||
| Thyroid dysgenesis | 194 | ||
| Thyroid dyshormonogenesis | 195 | ||
| General features | 195 | ||
| Sodium-iodine symporter defects | 196 | ||
| Pendred syndrome | 196 | ||
| Thyroperoxidase defects | 197 | ||
| Defects in H2O2 generation | 197 | ||
| Thyroglobulin defects | 197 | ||
| Dehalogenase defects | 197 | ||
| Abnormal thyroid hormone metabolism | 198 | ||
| Selenium incorporation defects | 198 | ||
| Thyroid hormone resistance | 198 | ||
| Receptor defects | 198 | ||
| Membrane transporter defects | 198 | ||
| Consumptive hypothyroidism | 199 | ||
| Hypothalamo-pituitary hypothyroidism | 199 | ||
| TRH defects | 199 | ||
| Isolated TSH deficiency | 199 | ||
| Transient neonatal hypothyroidism, hyperthyrotropinemia, and hypothyroxinemia | 200 | ||
| Evaluation of newborns with positive screening results | 200 | ||
| Treatment of congenital hypothyroidism | 201 | ||
| Congenital hyperthyroidism | 201 | ||
| Graves disease | 201 | ||
| Nonautoimmune hyperthyroidism | 202 | ||
| Disorders of thyroid hormone transport | 202 | ||
| References | 203 | ||
| 8 Disorders of calcium and phosphorus homeostasis in the newborn and infant | 209 | ||
| Calcium | 209 | ||
| Calcium sensing receptor | 209 | ||
| Phosphate | 220 | ||
| Phosphatonins | 221 | ||
| Magnesium | 221 | ||
| Alkaline phosphatase | 224 | ||
| Parathyroid hormone; parathyroid hormone–related protein; PTH/PTHRP receptors | 224 | ||
| Parathyroid hormone | 224 | ||
| Parathyroid hormone–related protein | 227 | ||
| Parathyroid hormone and parathyroid hormone–related protein receptors | 228 | ||
| Calcitonin | 230 | ||
| Vitamin D | 231 | ||
| Synthesis and biologic activity of vitamin D | 231 | ||
| Vitamin D receptor | 235 | ||
| Skeleton: Cartilage and bone | 239 | ||
| Cartilage and bone differentiation and formation | 239 | ||
| Chondrogenesis | 239 | ||
| Osteoblastogenesis | 242 | ||
| Osteoclastogenesis | 246 | ||
| Bone extracellular matrix and mineralization | 251 | ||
| Bone mineralization | 253 | ||
| Assessment of bone mass and strength | 258 | ||
| Mineral homeostasis during the life cycle | 265 | ||
| References | 269 | ||
| 9 Neonatal diabetes mellitus | 277 | ||
| Definition | 277 | ||
| Incidence | 277 | ||
| Clinical presentation | 279 | ||
| Classification | 279 | ||
| Transient neonatal diabetes mellitus (TNDM) | 280 | ||
| TNDM1 | 280 | ||
| TNDM-2 | 281 | ||
| Permanent neonatal diabetes mellitus (PNDM) | 283 | ||
| KATP and insulin gene mutations | 283 | ||
| Other genetic forms of PNDM | 284 | ||
| GCK | 284 | ||
| PDX-1 | 284 | ||
| HNF1β | 285 | ||
| Syndromic neonatal diabetes mellitus | 285 | ||
| Wollcott-rallison syndrome: Mutations in EIF2AK3 | 285 | ||
| IPEX-FOXP3 | 285 | ||
| GLIS 3 | 285 | ||
| PTF1A | 285 | ||
| Rfx6 | 285 | ||
| Neurog-3 | 286 | ||
| GATA6 | 286 | ||
| Diagnosis and treatment of neonatal diabetes mellitus | 286 | ||
| Available resources | 287 | ||
| Transition to oral therapy | 287 | ||
| Future directions | 287 | ||
| References | 288 | ||
| III Endocrine Disorders In Children And Adolescents | 291 | ||
| 10 Disorders of growth hormone/insulin-like growth factor secretion and action | 291 | ||
| Normal growth | 292 | ||
| Measurement | 292 | ||
| Growth charts | 293 | ||
| Body proportions | 301 | ||
| Skeletal maturation | 302 | ||
| Prediction of adult height | 303 | ||
| Parental target height | 304 | ||
| Endocrine regulation of growth | 304 | ||
| The pituitary | 304 | ||
| Growth hormone | 310 | ||
| Chemistry | 310 | ||
| Secretion | 311 | ||
| GH receptor/GH-binding protein | 312 | ||
| GH actions | 314 | ||
| Insulin-like growth factors | 315 | ||
| Historical background | 315 | ||
| IGF structure and molecular biology | 316 | ||
| Assay methodologies for the IGF peptides | 316 | ||
| Serum levels of IGF peptides | 317 | ||
| Measurement of IGF levels in growth disorders | 318 | ||
| IGF receptors | 318 | ||
| IGF-binding protein superfamily | 320 | ||
| Targeted disruption of components of the IGF system | 321 | ||
| Other growth factors | 322 | ||
| The FGF family of peptides and receptors | 322 | ||
| The EGF system | 323 | ||
| Other growth-promoting peptides | 323 | ||
| Growth inhibitory peptides | 324 | ||
| Sex steroids | 324 | ||
| Thyroid hormone | 324 | ||
| Growth retardation | 324 | ||
| Primary growth abnormalities | 324 | ||
| Osteochondrodysplasias | 324 | ||
| Achondroplasia. | 325 | ||
| Hypochondroplasia. | 326 | ||
| Chromosomal abnormalities | 326 | ||
| Down syndrome. | 326 | ||
| Turner syndrome. | 326 | ||
| 18q deletions. | 327 | ||
| Intrauterine growth retardation | 327 | ||
| Russell-silver syndrome (RSS). | 328 | ||
| Seckel syndrome. | 328 | ||
| Noonan syndrome. | 328 | ||
| Progeria. | 328 | ||
| Cockayne syndrome. | 328 | ||
| Microcephalic osteodysplastic primordial dwarfism. | 328 | ||
| Prader-willi syndrome. | 329 | ||
| Other genetic causes of short stature | 329 | ||
| Secondary growth disorders | 329 | ||
| Malnutrition | 329 | ||
| Chronic diseases | 330 | ||
| Malabsorption. | 330 | ||
| Cardiovascular disease. | 330 | ||
| Renal disease. | 330 | ||
| Hematologic disorders. | 331 | ||
| Diabetes mellitus. | 331 | ||
| Inborn errors of metabolism. | 331 | ||
| Pulmonary disease. | 331 | ||
| Chronic infection. | 331 | ||
| Endocrine disorders | 331 | ||
| Hypothyroidism. | 331 | ||
| Cushing syndrome. | 332 | ||
| Pseudohypoparathyroidism. | 332 | ||
| Rickets. | 332 | ||
| Vitamin D–resistant (hypophosphatemic) rickets. | 332 | ||
| IGF deficiency. | 332 | ||
| Hypothalamic dysfunction. | 333 | ||
| Molecular defects of GHRH or the GHRH receptor. | 336 | ||
| Trauma of the brain or hypothalamus. | 337 | ||
| Inflammation of the brain or hypothalamus. | 338 | ||
| Tumors of the brain or hypothalamus. | 339 | ||
| Optic gliomas | 339 | ||
| Cystic lesions | 339 | ||
| Irradiation of the brain or hypothalamus. | 340 | ||
| Pituitary GH deficiency. | 340 | ||
| Genetic abnormalities resulting in combined pituitary hormone deficiency. | 340 | ||
| Genetic abnormalities of GH production or secretion resulting in isolated GHD | 342 | ||
| Congenital abnormalities of the pituitary | 344 | ||
| Tumors involving the pituitary. | 344 | ||
| Psychosocial dwarfism. | 344 | ||
| GH neurosecretory dysfunction. | 345 | ||
| Acquired idiopathic isolated GHD. | 346 | ||
| Bio-inactive GH. | 346 | ||
| Primary IGFD and GH insensitivity(GHI). | 346 | ||
| GHR signaling defects. | 348 | ||
| ALS mutations. | 350 | ||
| IGFI gene defects. | 350 | ||
| IGFI receptor mutations. | 350 | ||
| Clinical features. | 355 | ||
| Diagnosis of IGF deficiency. | 356 | ||
| Provocative GH testing is nonphysiologic. | 357 | ||
| Arbitrary definitions of “subnormal” response to provocative tests. | 358 | ||
| Age dependency and use of sex steroids. | 358 | ||
| GH assays of limited accuracy. | 358 | ||
| Expense, discomfort, and risks of provocative GH testing. | 358 | ||
| Poor reproducibility of provocative tests. | 358 | ||
| Testing in the neonate. | 362 | ||
| Diagnosis of GHI. | 362 | ||
| Constitutional delay of growth and maturation. | 363 | ||
| Idiopathic short stature. | 363 | ||
| Treatment of growth disorders | 364 | ||
| Treatment of constitutional delay | 364 | ||
| Treatment of growth hormone deficiency | 364 | ||
| Dosing of GH | 365 | ||
| Novel modalities for treatment of GHD | 366 | ||
| Management of multiple pituitary hormone deficiency | 366 | ||
| Monitoring GH therapy | 367 | ||
| Monitoring serum IGF-1 levels | 367 | ||
| Role of serial bone age assessment | 367 | ||
| Assessment of treatment efficacy and optimizing growth response | 367 | ||
| Transition to adult management | 368 | ||
| Growth hormone treatment of other forms of short stature | 369 | ||
| Chronic renal failure | 369 | ||
| Turner syndrome | 369 | ||
| SHOX deficiency | 370 | ||
| Noonan syndrome | 370 | ||
| Down syndrome | 370 | ||
| Intrauterine growth retardation or small for gestational age | 371 | ||
| Prader-willi syndrome | 371 | ||
| Osteochondrodysplasias | 372 | ||
| Idiopathic short stature | 372 | ||
| Miscellaneous causes of growth failure | 373 | ||
| Normal aging and other catabolic states | 374 | ||
| Side effects of growth hormone | 374 | ||
| Development of leukemia | 374 | ||
| Recurrence of CNS tumors and occurrence of second malignancies | 374 | ||
| Pseudotumor cerebri | 374 | ||
| Slipped capital femoral epiphysis | 375 | ||
| Miscellaneous side effects | 375 | ||
| The question of long-term cancer risk | 375 | ||
| Treatment of primary severe IGFD: Use of IGF-i | 376 | ||
| Excess growth and tall stature | 378 | ||
| Tall stature and overgrowth syndromes | 378 | ||
| Overgrowth in the fetus | 379 | ||
| Tall stature and postnatal statural overgrowth | 380 | ||
| Differential diagnosis of tall stature | 380 | ||
| Precocious and delayed puberty | 381 | ||
| Diagnosing familial tall stature | 381 | ||
| Management of constitutional and syndromic tall stature | 381 | ||
| Excess GH secretion and pituitary gigantism | 382 | ||
| Diagnosis of GH excess | 382 | ||
| Treatment of GH oversecretion | 383 | ||
| Conclusions | 384 | ||
| References | 384 | ||
| 11 Disorders of the posterior pituitary | 405 | ||
| Introduction | 405 | ||
| Physiology of osmotic and volume regulation | 405 | ||
| Osmotic sensor and effector pathways | 405 | ||
| Vasopressin and oxytocin biochemistry | 405 | ||
| Regulation of vasopressin secretion and thirst | 408 | ||
| Osmotic regulation. | 408 | ||
| Nonosmotic regulation. | 409 | ||
| Vasopressin metabolism | 410 | ||
| Sites of vasopressin action | 410 | ||
| Volume sensor and effector pathways | 413 | ||
| Renin-angiotensin-aldosterone system | 413 | ||
| Endocrine renin-angiotensin-aldosterone system | 414 | ||
| Anatomy and biochemistry. | 414 | ||
| Regulation of secretion. | 414 | ||
| Local renin-angiotensin systems | 414 | ||
| Anatomy and biochemistry. | 414 | ||
| Regulation of secretion. | 415 | ||
| The natriuretic peptide system | 415 | ||
| Anatomy and biochemistry. | 415 | ||
| Regulation of secretion and action. | 416 | ||
| Approach to the patient: Differential diagnosis of disorders of water metabolism | 417 | ||
| Hyponatremia | 417 | ||
| Polyuria, polydipsia, and hypernatremia | 417 | ||
| Specific disorders of water metabolism | 419 | ||
| Hyponatremia with normal regulation of vasopressin | 419 | ||
| Hyponatremia with appropriate decreased secretion of vasopressin | 419 | ||
| Increased water ingestion (primary polydipsia). | 419 | ||
| Decreased renal free water clearance. | 419 | ||
| Treatment. | 421 | ||
| Hyponatremia with appropriate increased secretion of vasopressin | 421 | ||
| Causes | 421 | ||
| Systemic dehydration. | 421 | ||
| Primary loss of sodium chloride. | 421 | ||
| Decreased effective plasma volume. | 421 | ||
| Treatment. | 422 | ||
| Precautions in the emergency treatment of hyponatremia. | 422 | ||
| Hyponatremia with abnormal regulation of vasopressin | 423 | ||
| Hyponatremia with inappropriate increased secretion of vasopressin or increased vasopressin V2 receptor activity (syndrome ... | 423 | ||
| Causes of SIAD. | 423 | ||
| Treatment of siad. | 424 | ||
| Hyponatremia with inappropriate decreased secretion of vasopressin, due to increased secretion of atrial natriuretic peptide | 424 | ||
| Treatment of cerebral salt wasting | 425 | ||
| Other causes of true and factitious hyponatremia | 425 | ||
| Hypernatremia with inappropriate decreased vasopressin secretion or action | 425 | ||
| Central diabetes insipidus | 425 | ||
| Causes of central diabetes insipidus. | 425 | ||
| Genetic causes. | 425 | ||
| Trauma. | 425 | ||
| Neurosurgical intervention. | 426 | ||
| Congenital anatomic defects. | 426 | ||
| Neoplasms. | 426 | ||
| Infiltrative, autoimmune, and infectious diseases. | 426 | ||
| Brain death. | 427 | ||
| Increased metabolism of vasopressin. | 427 | ||
| Drugs. | 427 | ||
| Children with primary enuresis. | 427 | ||
| Treatment of central diabetes insipidus | 427 | ||
| Fluid therapy. | 427 | ||
| Vasopressin and vasopressin analogs. | 428 | ||
| Nephrogenic diabetes insipidus | 430 | ||
| Causes of nephrogenic diabetes insipidus. | 430 | ||
| Genetic causes. | 430 | ||
| Congenital, X-linked diabetes insipidus: V2 receptor mutations. | 430 | ||
| Congenital, autosomal nephrogenic diabetes insipidus: Aquaporin-2 mutations. | 430 | ||
| Acquired cause. | 431 | ||
| Treatment of nephrogenic diabetes insipidus. | 431 | ||
| Concluding remarks | 432 | ||
| References | 432 | ||
| 12 Thyroid disorders in children and adolescents | 444 | ||
| Introduction | 444 | ||
| Thyroid hormones and their action | 444 | ||
| Regulation of thyroid function | 446 | ||
| Clinical and biochemical assessment of thyroid status | 447 | ||
| Clinical evaluation of thyroid function | 447 | ||
| Biochemical evaluation of thyroid function | 448 | ||
| Hypothyroidism | 449 | ||
| Hashimoto or autoimmune thyroiditis | 449 | ||
| Hashitoxicosis | 450 | ||
| Subclinical hypothyroidism | 450 | ||
| Juvenile acquired hypothyroidism | 450 | ||
| Iodine-induced hypothyroidism | 451 | ||
| Hypothalamic-pituitary dysfunction | 452 | ||
| Giant hemangiomas | 452 | ||
| Hypothyroidism in cancer survivors | 452 | ||
| Thyroid hormone resistance | 452 | ||
| Hyperthyroidism | 453 | ||
| Graves disease | 453 | ||
| Medical therapy | 453 | ||
| Radioactive iodine therapy | 454 | ||
| Surgery | 455 | ||
| Stratification of treatment | 455 | ||
| Other causes of hyperthyroidism | 455 | ||
| Neonatal thyrotoxicosis | 455 | ||
| Infectious thyroiditis | 456 | ||
| Subacute thyroiditis | 456 | ||
| Hyperfunctioning nodules | 456 | ||
| Toxic multinodular goiters | 456 | ||
| Thyroid nodules and thyroid cancer | 457 | ||
| Nodule evaluation | 457 | ||
| Thyroid cancer | 457 | ||
| Surgical options | 459 | ||
| Radioactive iodine therapy | 459 | ||
| Levothyroxine therapy | 460 | ||
| Follow-up | 460 | ||
| Medullary thyroid carcinoma | 460 | ||
| Synopsis | 462 | ||
| References | 462 | ||
| 13 Adrenal cortex and its disorders | 471 | ||
| History, embryology, and anatomy | 471 | ||
| History | 472 | ||
| Embryology | 472 | ||
| Anatomy | 474 | ||
| Steroid hormone synthesis | 474 | ||
| Early steps: Cholesterol uptake, storage, and transport | 474 | ||
| Steroidogenic enzymes | 474 | ||
| Cytochrome P450 | 474 | ||
| Hydroxysteroid dehydrogenases | 475 | ||
| P450scc | 476 | ||
| Transport of electrons to P450scc: Adrenodoxin reductase and adrenodoxin | 476 | ||
| Mitochondrial cholesterol uptake: The steroidogenic acute regulatory protein, StARst | 476 | ||
| 3β-hydroxysteroid dehydrogenase/Δ5→Δ4 isomerase | 477 | ||
| P450c17 | 477 | ||
| Electron transport to P450c17: P450 oxidoreductase and cytochrome b5 | 477 | ||
| P450c21 | 478 | ||
| P450c11β and P450c11as | 478 | ||
| 17β-hydroxysteroid dehydrogenase | 479 | ||
| Steroid sulfotransferase and sulfatase | 479 | ||
| Aromatase: P450aro | 480 | ||
| 5α-reductase | 480 | ||
| 11β-hydroxysteroid dehydrogenase | 480 | ||
| 3α-hydroxysteroid dehydrogenases | 480 | ||
| Fetal adrenal steroidogenesis | 481 | ||
| Regulation of steroidogenesis | 482 | ||
| The hypothalamic-pituitary-adrenal axis | 482 | ||
| Hypothalamus: CRF and AVP | 482 | ||
| Pituitary: ACTH and POMC | 483 | ||
| Actions of ACTH | 483 | ||
| Diurnal rhythms of ACTH and cortisol | 484 | ||
| Adrenal: Glucocorticoid feedback | 484 | ||
| Mineralocorticoid secretion: The renin-angiotensin system | 484 | ||
| Adrenal androgen secretion and the regulation of adrenarche | 485 | ||
| Plasma steroids and their disposal | 486 | ||
| Structure and nomenclature | 486 | ||
| Circulating steroids | 486 | ||
| Steroid catabolism | 487 | ||
| Clinical and laboratory evaluation of adrenal function | 487 | ||
| Clinical evaluation | 487 | ||
| Laboratory evaluation | 487 | ||
| Plasma concentrations of cortisol and other steroids | 487 | ||
| Plasma renin | 489 | ||
| Urinary steroid excretion | 489 | ||
| Plasma ACTH and other POMC peptides | 490 | ||
| Secretory rates | 490 | ||
| Dexamethasone suppression test | 490 | ||
| Stimulation tests | 490 | ||
| Metyrapone test | 492 | ||
| Genetic lesions in steroidogenesis | 492 | ||
| Congenital lipoid adrenal hyperplasia | 492 | ||
| Disorders resembling lipoid cah: P450scc deficiency and sf1 deficiency | 495 | ||
| 3β-hydroxysteroid dehydrogenase deficiency | 495 | ||
| 17α-hydroxylase/17,20-lyase deficiency | 496 | ||
| P450 oxidoreductase deficiency | 497 | ||
| Cytochrome B5 deficiency | 498 | ||
| 21-hydroxylase deficiency | 498 | ||
| Pathophysiology | 498 | ||
| Clinical forms of 21-hydroxylase deficiency | 499 | ||
| Salt-wasting CAH. | 500 | ||
| Simple virilizing CAH. | 500 | ||
| Nonclassic CAH. | 500 | ||
| Incidence of 21-hydroxylase deficiency | 500 | ||
| Genetics of the 21-hydroxylase locus | 501 | ||
| 21-hydroxylase genes. | 501 | ||
| HLA linkage. | 501 | ||
| Other genes in the 21-hydroxylase locus. | 502 | ||
| P450c21 gene lesions causing 21-hydroxylase deficiency | 502 | ||
| Mapping of P450c21 genes in normals and in CAH. | 502 | ||
| Gene conversions and microconversions causing CAH. | 502 | ||
| Mutations causing simple virilizing and nonclassic CAH. | 503 | ||
| Prenatal diagnosis of CAHst | 503 | ||
| Diagnosis | 503 | ||
| Treatment | 504 | ||
| Experimental prenatal treatment of CAH | 505 | ||
| Experimental postnatal treatment of CAH | 506 | ||
| Antiandrogens and aromatase inhibitors. | 506 | ||
| Adrenalectomy. | 506 | ||
| Growth hormone and GnRH agonist therapy. | 506 | ||
| Lesions in isozymes of P450c11 | 506 | ||
| 11β-hydroxylase deficiency | 506 | ||
| Corticosterone methyl oxidase deficiencies | 507 | ||
| Glucocorticoid-suppressible hyperaldosteronism | 507 | ||
| Lesions in isozymes of 11β-hydroxysteroid dehydrogenase | 508 | ||
| Lesions in 11βhsd1: (Apparent) Cortisone Reductase Deficiency | 508 | ||
| Lesions in 11βhsd2: Apparent mineralocorticoid excess (AME) | 508 | ||
| Adrenal insufficiency | 508 | ||
| Acute primary adrenal insufficiency | 508 | ||
| Chronic primary adrenal insufficiency | 509 | ||
| Autoimmune disorders | 509 | ||
| Type 1 autoimmune polyendocrine syndrome. | 510 | ||
| Type 2 autoimmune polyendocrine syndrome. | 510 | ||
| Adrenal hypoplasia congenita | 510 | ||
| X-linked adrenal hypoplasia congenita. | 510 | ||
| Autosomal forms of adrenal hypoplasia. | 511 | ||
| IMAGe syndrome. | 511 | ||
| ACTH resistance syndromes | 511 | ||
| MC2R mutations: Familial glucocorticoid deficiency type 1 (FGD1). | 511 | ||
| MRAP mutations: Familial glucocorticoid deficiency type2 (FGD2). | 511 | ||
| Other forms of familial glucocorticoid deficiency. | 511 | ||
| Triple A (Allgrove) syndrome. | 512 | ||
| Metabolic disorders | 512 | ||
| Adrenoleukodystrophy (ALD). | 512 | ||
| Peroxisome biogenesis disorders. | 512 | ||
| Wolman disease. | 513 | ||
| Smith-lemli-opitz syndrome. | 513 | ||
| Mitochondrial disorders. | 513 | ||
| Other causes | 513 | ||
| Secondary adrenal insufficiency | 514 | ||
| Hypothalamic causes | 514 | ||
| ACTH deficiency | 514 | ||
| Disorders of POMC | 515 | ||
| Long-term steroid therapy | 515 | ||
| Adrenal excess | 515 | ||
| Cushing syndrome | 515 | ||
| Clinical findings | 515 | ||
| Cushing disease | 516 | ||
| Other causes of cushing syndrome | 517 | ||
| Ectopic ACTH syndrome. | 517 | ||
| Adrenal tumors. | 517 | ||
| ACTH-independent multinodular adrenal hyperplasias. | 518 | ||
| Differential diagnosis | 518 | ||
| Virilizing and feminizing adrenal tumors | 520 | ||
| Other disorders | 520 | ||
| Primary hyperaldosteronism: Conn syndrome | 520 | ||
| Familial glucocorticoid resistance | 520 | ||
| Pseudohypoaldosteronism | 521 | ||
| Glucocorticoid therapy and withdrawal | 521 | ||
| Replacement therapy | 522 | ||
| Commonly used glucocorticoid preparations | 523 | ||
| Pharmacologic therapy | 524 | ||
| Withdrawal of glucocorticoid therapy | 524 | ||
| Stress doses of glucocorticoids | 525 | ||
| Mineralocorticoid replacement | 525 | ||
| Concluding remarks | 526 | ||
| References | 526 | ||
| Pheochromocytoma and multiple endocrine neoplasia syndromes | 533 | ||
| Introduction | 533 | ||
| Genetic counseling and testing | 533 | ||
| Pheochromocytoma and paraganglioma | 534 | ||
| Biosynthesis and actions of catecholamines | 536 | ||
| Clinical presentation | 536 | ||
| Evaluation | 538 | ||
| Biochemical diagnosis | 538 | ||
| Radiographic studies | 539 | ||
| Genetic issues | 540 | ||
| Management | 540 | ||
| Surgical therapy | 540 | ||
| Medical preparation for surgery | 540 | ||
| Prognosis and follow-up | 541 | ||
| Medullary thyroid carcinoma | 542 | ||
| Clinical presentation | 544 | ||
| Evaluation and management | 544 | ||
| Prognosis | 544 | ||
| Hereditary endocrine neoplasia syndromes | 544 | ||
| Carney complex | 544 | ||
| Familial isolated pituitary adenomas | 545 | ||
| Familial paraganglioma syndromes | 546 | ||
| Hyperparathyroidism-jaw tumor syndrome | 546 | ||
| Multiple endocrine neoplasia 1 (men1) | 546 | ||
| Epidemiology and pathogenesis | 546 | ||
| Clinical presentation and management | 547 | ||
| Primary hyperparathyroidism | 548 | ||
| Gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) | 549 | ||
| Gastrinoma. | 549 | ||
| Insulinoma. | 549 | ||
| Glucagonoma. | 550 | ||
| VIPoma. | 550 | ||
| Nonfunctioning pancreatic neuroendocrine tumors (NfpNETs). | 550 | ||
| Pituitary adenomas | 550 | ||
| Other clinical manifestations | 550 | ||
| Carcinoid tumors. | 550 | ||
| Adrenocortical tumors. | 551 | ||
| Cutaneous manifestations. | 551 | ||
| Genetic testing and presymptomatic screening | 551 | ||
| Multiple endocrine neoplasia 2 (MEN2) | 552 | ||
| Multiple endocrine neoplasia 4 (MEN4) | 555 | ||
| Von hippel-lindau disease | 555 | ||
| Other tumor syndromes associated with endocrine neoplasia | 555 | ||
| APC-associated polyposis | 555 | ||
| Beckwith-wiedemann syndrome | 556 | ||
| Carney triad | 556 | ||
| Li-fraumeni syndrome | 556 | ||
| Neurofibromatosis type 1 | 556 | ||
| Peutz-Jeghers syndrome | 557 | ||
| PTEN hamartoma tumor syndrome | 557 | ||
| Tuberous sclerosis complex | 557 | ||
| Summary and future developments | 557 | ||
| References | 558 | ||
| 15 Puberty and its disorders in the female | 569 | ||
| Introduction | 569 | ||
| Development of the female reproductive system | 570 | ||
| Maturation of the neuroendocrine-ovarian axis | 570 | ||
| Fetus | 570 | ||
| Neuroendocrine unit. | 570 | ||
| Ovary. | 571 | ||
| Placenta. | 572 | ||
| Infant and child | 573 | ||
| Neuroendocrine unit. | 573 | ||
| Ovary. | 574 | ||
| Adolescent | 575 | ||
| Adult | 578 | ||
| Follicular (proliferative) phase ovary. | 580 | ||
| Luteal (secretory) phase ovary. | 582 | ||
| Regulation of the neuroendocrine-ovarian axis | 582 | ||
| Factors controlling the onset of puberty | 582 | ||
| Regulation of gonadotropin secretion | 586 | ||
| Regulation of ovarian secretion | 588 | ||
| Adrenarche and the regulation of adrenal androgen secretion | 589 | ||
| Hormonal secretion, transport, metabolism, and action | 590 | ||
| Peptide hormones | 590 | ||
| Steroid hormones | 592 | ||
| Maturation of sex hormone target organs | 592 | ||
| Genital tract | 592 | ||
| Mammary glands | 598 | ||
| Pilosebaceous unit | 598 | ||
| Bone | 599 | ||
| Adipose tissue | 599 | ||
| Central nervous system | 599 | ||
| Other targets of sex hormone action | 600 | ||
| Normal sexual maturation: Hormonal and physical stages | 601 | ||
| The fetus and neonate | 601 | ||
| Childhood | 601 | ||
| Adolescence | 601 | ||
| Hormonal | 601 | ||
| Clinical | 602 | ||
| Adult menstrual cycle | 603 | ||
| Normal variations in pubertal development | 603 | ||
| Premature thelarche | 603 | ||
| Premature pubarche | 603 | ||
| Constitutional delay of pubertal development | 604 | ||
| Physiologic adolescent anovulation | 604 | ||
| Other normal adolescent variations | 605 | ||
| Abnormal puberty | 606 | ||
| Abnormal development | 606 | ||
| Disorders of sex development | 606 | ||
| Other dysgenetic disorders | 607 | ||
| Precocious puberty | 607 | ||
| Causes | 607 | ||
| Complete precocious puberty. | 607 | ||
| Incomplete precocity. | 609 | ||
| Differential diagnosis | 612 | ||
| Management | 613 | ||
| Hypogonadism | 615 | ||
| Causes | 615 | ||
| Primary ovarian failure. | 615 | ||
| Gonadotropin deficiency (hypogonadotropic hypogonadism). | 617 | ||
| Differential diagnosis | 621 | ||
| Management | 625 | ||
| Nonhypoestrogenic menstrual disturbances | 627 | ||
| Hypothalamic anovulation | 627 | ||
| Causes. | 628 | ||
| Differential diagnosis. | 628 | ||
| Management. | 629 | ||
| Dysfunctional uterine bleeding | 629 | ||
| Causes. | 629 | ||
| Differential diagnosis. | 630 | ||
| Management. | 630 | ||
| Perimenstrual symptoms | 631 | ||
| Dysmenorrhea. | 631 | ||
| Premenstrual syndrome. | 631 | ||
| Hyperandrogenism in adolescence | 631 | ||
| Causes | 632 | ||
| Polycystic ovary syndrome. | 632 | ||
| Clinical manifestations (figure 15-44). | 632 | ||
| Laboratory manifestations (see figure 15-44). | 633 | ||
| Pathogenesis. | 634 | ||
| Etiology. | 635 | ||
| Other causes of functional ovarian hyperandrogenism. | 635 | ||
| Other causes of functional adrenal hyperandrogenism. | 635 | ||
| Peripheral androgen overproduction. | 636 | ||
| Tumoral hyperandrogenism. | 636 | ||
| Androgenic drugs. | 636 | ||
| Differential diagnosis. | 636 | ||
| Diagnostic approach | 636 | ||
| Management | 641 | ||
| Future directions | 642 | ||
| References | 643 | ||
| 16 Turner syndrome | 664 | ||
| Historical background | 664 | ||
| Genetics | 665 | ||
| Chromosomal origins | 665 | ||
| Epidemiology | 665 | ||
| Turner karyotypes | 667 | ||
| X chromosome genes and turner syndrome | 667 | ||
| X chromosome genomic imprinting | 668 | ||
| Diagnostic tests | 669 | ||
| Indications for karyotype testing | 669 | ||
| Differential diagnosis | 670 | ||
| Prenatal diagnosis | 670 | ||
| Phenotypic features | 671 | ||
| Lymphatic obstruction | 672 | ||
| Skeletal anomalies and short stature | 673 | ||
| Ovarian insufficiency | 675 | ||
| Gonadoblastoma | 676 | ||
| Cardiovascular system | 676 | ||
| Spectrum and etiology of congenital cardiovascular malformations | 676 | ||
| Aortic complications | 677 | ||
| Other cardiovascular issues | 678 | ||
| Cardiovascular screening in turner syndrome | 678 | ||
| Ongoing cardiac care | 679 | ||
| Risk for premature atherosclerotic disease | 680 | ||
| Renal anomalies | 680 | ||
| Otologic disorders | 680 | ||
| Autoimmunity | 681 | ||
| Gastrointestinal disorders | 681 | ||
| Liver disease | 681 | ||
| Gastrointestinal bleeding | 681 | ||
| Inflammatory bowel disease | 682 | ||
| Carbohydrate intolerance | 682 | ||
| Neuropsychological features | 682 | ||
| Medical management | 683 | ||
| Initial and follow-up evaluation | 683 | ||
| Y chromosome | 684 | ||
| Growth hormone | 685 | ||
| Puberty | 687 | ||
| Reproductive options | 690 | ||
| Transition to adult care | 690 | ||
| References | 690 | ||
| 17 Puberty and its disorders in the male | 697 | ||
| Prenatal neurobiology of puberty | 698 | ||
| Testicular differentiation and development | 698 | ||
| Prenatal testicular development | 698 | ||
| Postnatal testicular development | 699 | ||
| The androgen receptor | 699 | ||
| Physiology of puberty | 700 | ||
| Endocrinology | 700 | ||
| Neuroendocrine regulation of pubertal onset | 701 | ||
| Somatic changes | 701 | ||
| Regulation of the timing of puberty | 702 | ||
| Genetics | 702 | ||
| Genetic disorders causing GnRH deficiency | 702 | ||
| Normosmic hypogonadotropic hypogonadism | 702 | ||
| Kallmann syndrome | 702 | ||
| Other genes associated with HH | 703 | ||
| Genetic variation in normal puberty | 703 | ||
| Candidate gene-based studies | 703 | ||
| Genome-wide association (GWA) studies | 703 | ||
| External factors and secular trends in the timing of puberty | 704 | ||
| Effect of BMI on pubertal timing | 704 | ||
| Effect of endocrine disrupting chemicals | 705 | ||
| Precocious puberty | 705 | ||
| GnRH-dependent forms of precocious puberty | 705 | ||
| GnRH-independent forms of precocious puberty | 706 | ||
| Evaluation of the boy with precocious development of secondary sexual characteristics | 708 | ||
| Treatment of the child with precocious puberty | 709 | ||
| Central precocious puberty | 709 | ||
| Peripheral precocity | 709 | ||
| Delayed puberty | 710 | ||
| Etiologies of delayed puberty | 710 | ||
| CDGP | 710 | ||
| Hypogonadotropic hypogonadism | 711 | ||
| Pituitary-dependent hypogonadism | 712 | ||
| Hypothalamic and pituitary-dependent hypogonadism | 712 | ||
| Functional hypogonadotropic hypogonadism | 712 | ||
| Hypergonadotropic hypogonadism | 713 | ||
| Klinefelter syndrome | 713 | ||
| XX males | 714 | ||
| Gonadal dysgenesis | 714 | ||
| Syndromes associated with delayed puberty | 714 | ||
| Defects in steroidogenesis or steroid hormone action | 715 | ||
| Chemotherapy, radiation therapy, and cancer survival | 716 | ||
| Other disorders of the male reproductive endocrine axis | 716 | ||
| Androgen Receptor (AR) mutations | 716 | ||
| Persistent mullerian duct syndrome | 717 | ||
| Testicular regression syndrome (anorchia), cryptorchidism, and hypospadias | 717 | ||
| Testis tumors | 718 | ||
| Germ cell tumors | 718 | ||
| Nongerm cell tumors | 718 | ||
| Gynecomastia | 719 | ||
| Evaluation of the child with delayed puberty | 719 | ||
| Initial evaluation | 719 | ||
| History | 719 | ||
| Physical examination | 723 | ||
| Testing | 723 | ||
| Additional evaluation | 723 | ||
| Treatment of delayed puberty | 724 | ||
| Testosterone: The hypogonadal male athlete and the individual with a DSD | 725 | ||
| Conclusion | 726 | ||
| References | 726 | ||
| 18 Disorders of mineral homeostasis in children and adolescents | 734 | ||
| Hypocalcemia | 734 | ||
| Hypocalcemia in the neonate and infant | 734 | ||
| Early neonatal hypocalcemia | 734 | ||
| Late neonatal hypocalcemia | 738 | ||
| Hypoparathyroidism | 742 | ||
| Evaluation and management | 746 | ||
| Hypocalcemia in the child and adolescent | 749 | ||
| Etiology | 749 | ||
| Evaluation | 753 | ||
| Management | 754 | ||
| Hypercalcemia | 755 | ||
| Hypercalcemia in the neonate and infant | 755 | ||
| Etiology | 755 | ||
| Evaluation and management | 760 | ||
| Hypercalcemia in the child and adolescent | 762 | ||
| Etiology | 762 | ||
| Evaluation | 768 | ||
| Management | 770 | ||
| Disorders of magnesium metabolism | 772 | ||
| Hypomagnesemia | 772 | ||
| Hypermagnesemia | 774 | ||
| Disorders of skeletal mineralization | 775 | ||
| Disorders of bone mineralization in the neonate and infant | 775 | ||
| Low bone mass/rickets | 775 | ||
| Increased bone mass | 778 | ||
| Disorders of bone mineralization and formation in the child and adolescent | 779 | ||
| Rickets | 779 | ||
| Calciopenic rickets. | 781 | ||
| Phosphopenic rickets. | 787 | ||
| Disorders of alkaline phosphatase activity. | 795 | ||
| Chronic kidney disease-mineral and bone disorder | 797 | ||
| Disorders of bone mineralization | 798 | ||
| Low bone mass | 799 | ||
| Evaluation and management of low bone mass | 807 | ||
| Osteogenesis imperfecta | 809 | ||
| Fibrous dysplasia | 814 | ||
| High bone mass | 815 | ||
| Heterotopic bone formation/ectopic calcification | 822 | ||
| Osteochondrodysplasias | 824 | ||
| Concluding remarks | 831 | ||
| Addendum | 831 | ||
| References | 833 | ||
| 19 Diabetes mellitus | 846 | ||
| Introduction | 846 | ||
| Classification | 847 | ||
| Type 1 diabetes mellitus | 849 | ||
| Type 2 diabetes | 849 | ||
| Type 1 diabetes mellitus | 850 | ||
| Epidemiology | 850 | ||
| Etiology, pathogenesis, and genetics | 850 | ||
| Prediction and prevention | 857 | ||
| Insulin biosynthesis | 858 | ||
| Insulin secretion | 859 | ||
| Insulin action | 861 | ||
| Pathophysiology | 863 | ||
| Clinical manifestations of diabetes mellitus | 864 | ||
| Diagnosis | 866 | ||
| Diabetic ketoacidosis | 867 | ||
| Treatment of diabetes mellitus | 868 | ||
| Treatment of diabetic ketoacidosis | 868 | ||
| Fluid and electrolyte therapy | 868 | ||
| Cerebral edema | 869 | ||
| Electrolytes | 870 | ||
| Alkali therapy | 871 | ||
| Insulin therapy | 871 | ||
| Treatment of type 1 diabetes mellitus (t1dm) | 872 | ||
| General principles | 872 | ||
| Goals of therapy | 872 | ||
| Types of insulin | 872 | ||
| Human regular insulin | 873 | ||
| Rapid-acting analogs | 873 | ||
| Intermediate-acting insulin | 873 | ||
| Long-acting insulin analogs | 873 | ||
| Premixed insulin | 874 | ||
| Syringes versus pens | 874 | ||
| Initiating insulin therapy | 874 | ||
| Insulin regimens | 874 | ||
| Multiple daily injection (MDI) regimens | 874 | ||
| Insulin pump therapy | 875 | ||
| Indications for pumps in pediatrics | 876 | ||
| Pump features | 876 | ||
| Nph-based treatment regimens | 876 | ||
| Blood glucose monitoring | 877 | ||
| Continuous glucose monitoring | 877 | ||
| Medical nutrition therapy | 877 | ||
| Exercise | 878 | ||
| Residual β-cell function (the honeymoon period) | 878 | ||
| Hypoglycemia | 879 | ||
| Sick day management | 880 | ||
| Associated autoimmune diseases | 880 | ||
| Associated psychosocial problems | 880 | ||
| Outpatient care | 881 | ||
| Management during surgery | 882 | ||
| The future is now: Closed-loop insulin delivery | 882 | ||
| Non-autoimmune type 1 diabetes | 883 | ||
| Csii-based treatment regiments | 883 | ||
| Basal insulin rates | 884 | ||
| Verifying basal insulin rate settings | 885 | ||
| Temporary basal rates and basal insulin suspend | 885 | ||
| Bolus insulin dosages | 885 | ||
| Bolus insulin for food coverage | 885 | ||
| Bolus insulin for correction of hyperglycemia | 886 | ||
| Specific considerations and acute complications of insulin pump therapy | 886 | ||
| Insulin pump therapy in kindergarten and school | 886 | ||
| Type 2 diabetes mellitus | 887 | ||
| Typical | 887 | ||
| Genetic defects of beta cell function | 888 | ||
| Mody syndromes | 888 | ||
| Other forms of monogenic diabetes | 888 | ||
| Mitochondrial diabetes | 888 | ||
| Wolfram syndrome | 889 | ||
| Thiamine-responsive diabetes mellitus (roger syndrome) | 890 | ||
| Drug or chemical induced | 890 | ||
| Diseases of the exocrine pancreas | 890 | ||
| Ionizing radiation to the abdomen | 890 | ||
| Pancreatectomy | 890 | ||
| Virus infections | 890 | ||
| Genetic defects in insulin action | 891 | ||
| Type A insulin resistance with acanthosis nigricans | 891 | ||
| Type B insulin resistance | 891 | ||
| Leprechaunism (donohue syndrome) | 891 | ||
| Rabson-mendenhall syndrome | 891 | ||
| Lipoatrophic diabetes | 891 | ||
| Acquired defects in insulin action | 891 | ||
| Genetic syndromes with diabetes and insulin resistance or insulin deficiency | 892 | ||
| Gestational diabetes | 892 | ||
| Neonatal diabetes | 892 | ||
| Impaired glucose tolerance | 893 | ||
| Pancreas and islet transplantation | 893 | ||
| Concluding remarks | 893 | ||
| References | 894 | ||
| 20 Autoimmune polyglandular syndromes | 901 | ||
| Index | 1035 | ||
| A | 1035 | ||
| B | 1037 | ||
| C | 1038 | ||
| D | 1040 | ||
| E | 1041 | ||
| F | 1042 | ||
| G | 1043 | ||
| H | 1045 | ||
| I | 1048 | ||
| J | 1049 | ||
| K | 1049 | ||
| L | 1049 | ||
| M | 1050 | ||
| N | 1051 | ||
| O | 1052 | ||
| P | 1053 | ||
| Q | 1055 | ||
| R | 1056 | ||
| S | 1056 | ||
| T | 1058 | ||
| U | 1060 | ||
| V | 1060 | ||
| W | 1060 | ||
| X | 1061 | ||
| Y | 1061 | ||
| Z | 1061 | ||
| Inside back cover | 1 |