HUMAN GROWTH HORMONE
SECTION I: GROWTH AND GROWTH DISORDERS 1 WORRISOME GROWTH / INTRODUCTION / SIGNI?CANCE OF WORRISOME GROWTH / DIAGNOSIS OF SHORT STATURE / THE DIFFERENTIAL DIAGNOSES OF WORRISOME GROWTH / CONSTITUTIONAL GROWTH DELAY / FAMILIAL SHORT STATURE / PATHOLOGICAL (SYNDROMIC) SHORT STATURE / INTRAUTERINE GROWTH RETARDATION / FAILURE TO THRIVE / NUTRITIONAL GROWTH RETARDATION (NGR) / LABORATORY AIDS IN DIFFERENTIATING SHORT STATURE / FINAL CONSIDERATIONS / REFERENCES / 2 IDIOPATHIC SHORT STATURE / HISTORICAL CONSIDERATIONS—THE BIRTH OF THE TERM IDIOPATHIC SHORT STATURE / GROWTH HORMONE-INSULIN-LIKE GROWTH FACTOR AXIS IN IDIOPATHIC SHORT STATURE / THE MOLECULAR BASIS OF IDIOPATHIC SHORT STATURE / THE SPECTRUM OF GROWTH HORMONE-INSULIN-LIKE GROWTH FACTOR DE?CIENCY IN IDIOPATHIC SHORT STATURE / DIAGNOSIS OF IDIOPATHIC SHORT STATURE / RATIONALE AND MANAGEMENT OF IDIOPATHIC SHORT STATURE / PSYCHOSOCIAL AND ETHICAL CONSIDERATIONS / FUTURE DIRECTIONS / 3 HYPOPITUITARISM AND OTHER DISORDERS OF THE GROWTH HORMONE–INSULIN-LIKE GROWTH FACTOR-I AXIS / PITUITARY GLAND / GH-IGH-I AXIS / CLASSI?CATION OF DISORDERS INVOLVING THE GH–IGF-I AXIS / IGF-I DE?CIENCY DUE TO CONGENITAL GHD / ACQUIRED GHD / IGF-I DE?CIENCY DUE TO GH RECEPTOR/ POST-RECEPTOR ABNORMALITY / EVALUATION / TREATMENT / 4 GROWTH HORMONE–DE?CIENCY IN THE ADULT: TRANSITION FROM ADOLESCENCE TO ADULTHOOD / FINAL ADULT HEIGHT REACHED BY CHILDREN WITH GROWTH HORMONE DE?CIENCY / TRANSITION FROM CHILDHOOD TO ADULTHOOD GROWTH HORMONE DE?CIENCY / ADULT GROWTH HORMONE DE?CIENCY / THERAPY / CONCLUSIONS / 5 GROWTH HORMONE TREATMENT / GROWTH HORMONE PHYSIOLOGY / GROWTH HORMONE EFFECTS / GROWTH HORMONE DE?CIENCY / TREATMENT OF GROWTH HORMONE DE?CIENCY / CAUSES OF SHORT STATURE OTHER THAN GROWTH HORMONE- DE?CIENCY THAT MAY RESPOND TO GROWTH HORMONE TREATMENT / ADVERSE EFFECTS OF GROWTH HORMONE TREATMENT / ETHICAL ISSUES OF GROWTH HORMONE TREATMENT / 6 THE SKELETAL DYSPLASIAS / DIFFERENTIATION OF THE SKELETAL DYSPLASIAS / DIAGNOSIS AND ASSESSMENT / MOLECULAR STUDIES AND MECHANISM OF SHORT STATURE IN SKELETAL DYSPLASIAS / MANAGEMENT / 7 OVERGROWTH SYNDROMES: EVALUATION AND MANAGEMENT OF THE CHILD WITH EXCESSIVE LINEAR GROWTH / GROWTH EPOCHS / THE CELL CYCLE / MECHANISMS OF LONGITUDINAL GROWTH / NUTRITIONAL EFFECTS ON GROWTH / INTRINSIC/CONSTITUTIONAL (FAMILIAL, GENETIC) TALL STATURE / GROWTH HORMONE EXCESS / DISORDERS OF PUBERTAL DEVELOPMENT / HYPERINSULINISM / FAMILIAL GLUCOCORTICOID DE?CIENCY / OVERGROWTH SYNDROMES / SECTION II: ADRENAL DISORDERS AND SEXUAL DEVELOPMENT ABNORMALITIES 8 ADRENAL CORTEX: HYPO- AND HYPERFUNCTION / PHYSIOLOGY / HYPOADRENOCORTICISM / PRIMARY HYPOADRENOCORTICISM—CONGENITAL FORMS / PRIMARY HYPOADRENOCORTICISM—ACQUIRED FORMS / SECONDARY HYPOADRENOCORTICISM DUE TO DE?CIENT CRH AND/OR ACTH SECRETION / HYPOADRENOCORTICISM SECONDARY TO END-ORGAN UNRESPONSIVENESS / TREATMENT OF HYPOADRENOCORTICISM / ISOLATED MINERALOCORTICOID DE?CIENCY CAUSED BY MUTATIONS OF CYP11B2 GENE / STEROID SULFATASE DE?CIENCY (X-LINKED ICHTHYOSIS) / HYPERADRENOCORTICISM / HYPERCORTISOLISM / VIRILIZED ADRENAL TUMORS / FEMINIZING ADRENAL TUMORS / HYPERALDOSTERONISM / 9 AN UPDATE OF CONGENITAL ADRENAL HYPERPLASIA / PATHOPHYSIOLOGY / CLINICAL FEATURES / CLINICAL FORMS OF ADRENAL HYPERPLASIA CAUSED BY 21-HYDROXYLASE DE?CIENCY / CONTENTS PUBERTAL MATURATION IN CLASSICAL CONGENITAL ADRENAL HYPERPLASIA / GENETICS / EPIDEMIOLOGY / DIAGNOSIS / HORMONAL STANDARDS FOR DIAGNOSING 21-HYDROXYLASE DE?CIENCY / NEW TREATMENT STRATEGIES / PSYCHOLOGICAL ASPECTS OF CAH / CONCLUSION / 10 DISORDERS OF THE ADRENAL MEDULLA-CATECHOLAMINE PRODUCING TUMORS IN CHILDHOOD / CHROMAF?N CELL BIOLOGY / PHEOCHROMOCYTOMA / NEUROBLASTOMA / GANGLIONEUROMA / NEURAL TUMORS AND CHRONIC DIARRHEA / 11 PUBERTY AND ITS DISORDERS / NORMAL PUBERTY / NORMAL FEMALE DEVELOPMENT / NORMAL MALE DEVELOPMENT / PRECOCIOUS PUBERTY / ETIOLOGIES OCCURRING IN BOTH SEXES / TREATMENT OF UNDERLYING ABNORMALITIES OF PRECOCIOUS PUBERTY / OTHER FORMS OF EARLY OR GENDER-INAPPROPRIATE DEVELOPMENT / DELAYED PUBERTY AND HYPOGONADISM / 12 TURNER SYNDROME / FEATURES OF TURNER SYNDROME / THE GENETIC BASIS OF TURNER SYNDROME / MEDICAL THERAPIES / 13 HIRSUTISM AND POLYCYSTIC OVARY SYNDROME / STEROIDOGENESIS / PUBERTY: ADRENARCHE AND GONADARCHE / EXCESSIVE BODY HAIR / ADRENAL CAUSES OF HYPERANDROGENISM / POLYCYSTIC OVARY SYNDROME / SUMMARY AND CONCLUSIONS / 14 ADOLESCENT MENSTRUAL ABNORMALITIES / NORMAL PUBERTAL DEVELOPMENT AND MENARCHE / MENSTRUAL DISORDERS / DIAGNOSIS AND HISTORY / 15 DISORDERS OF SEXUAL DIFFERENTIATION / GONADAL DIFFERENTIATION / ANATOMIC SEX DIFFERENTIATION OF THE REPRODUCTIVE TRACT / HORMONAL CONTROL OF SEX DIFFERENTIATION / AMBIGUOUS GENITALIA / DIAGNOSTIC EVALUATION FOR AMBIGUOUS GENITALIA / MANAGEMENT OF INTERSEX / MICROPENIS / HYPOSPADIAS / CRYPTORCHIDISM / SECTION III: THYROID DISORDERS 16 THYROID DISORDERS IN INFANCY / CHANGES IN THYROID HORMONE ECONOMY FROM CONCEPTION TO THREE YEARS OF AGE / CONGENITAL HYPOTHYROIDISM / HYPOTHYROXINEMIA OF THE NEWBORN / CONGENITAL HYPERTHYROIDISM / ACQUIRED HYPO- AND HYPERTHYROIDISM IN INFANCY / STRUCTURAL THYROID PROBLEMS / 17 HYPOTHYROIDISM / CLASSI?CATION AND TERMINOLOGY / PRIMARY HYPOTHYROIDISM / CENTRAL HYPOTHYROIDISM / RESISTANCE TO THYROID HORMONE / CONSUMPTIVE HYPOTHYROIDISM / CLINICAL PRESENTATION / 18 HYPERTHYROIDISM / OVERVIEW / GRAVES’ DISEASE / AUTONOMOUS THYROID NODULE / FAMILIAL NONAUTOIMMUNE HYPERTHYROIDISM / TSH-INDUCED HYPERTHYROIDISM / SUBACUTE AND HASHIMOTO’S THYROIDITIS / EXOGENOUS THYROID HORMONE / HUMAN CHORIONIC GONADOTROPIN–INDUCED HYPERTHYROIDISM / EUTHYROID HYPERTHYROXINEMIA / T3 AND T4 TOXICOSIS / GRAVES’ OPHTHALMOPATHY / LABORATORY EVALUATION / PROGNOSIS AND TREATMENT / 19 THYROMEGALY / CAUSES OF GOITER / THERAPY OF NONTOXIC DIFFUSE GOITER / 20 THYROID TUMORS IN CHILDREN / PREDISPOSING FACTORS / PATHOLOGY / PATHOGENESIS / SECTION IV: DISORDERS OF CALCIUM AND MINERAL METABOLISM 21 CALCIUM DISORDERS IN CHILDREN AND ADOLESCENTS / HORMONAL REGULATION OF SERUM CA2Þ / CALCIOTROPIC HORMONES / HYPOCALCEMIA / HYPERCALCEMIA / 22 NEONATAL CALCIUM, MAGNESIUM, AND PHOSPHORUS DISORDERS / NORMAL CIRCULATING CONCENTRATION / PHYSIOLOGIC CONTROL OF MINERAL HOMEOSTASIS / DISTURBANCES IN SERUM MINERAL CONCENTRATIONS / SKELETAL MANIFESTATIONS OF DISTURBED MINERAL HOMEOSTASIS / 23 RICKETS AND OSTEOPOROSIS / RICKETS / VITAMIN D PSEUDODE?CIENCY / HEREDITARY 1,25-DIHYDROXYVITAMIN D–RESISTANT RICKETS / HYPOPHOSPHATEMIC SYNDROMES / HYPOPHOSPHATASIA / VITAMIN D TOXICITY / OSTEOPOROSIS / IDIOPATHIC JUVENILE OSTEOPOROSIS / SECONDARY OSTEOPOROSIS IN PEDIATRICS / 24 SYNDROMES WITH BRITTLE BONES, HYPEROSTOTIC BONE DISEASES, AND FIBROUS DYSPLASIA OF BONE / OSTEOGENESIS IMPERFECTA (BRITTLE BONES DISEASE) / SYNDROMES RESEMBLING OSTEOGENESIS IMPERFECTA / OSTEOPETROSIS AND OTHER SCLEROSING BONE DISEASES / FIBROUS DYSPLASIA OF BONE / TREATMENT OF LOW BONE DENSITY IN PEDIATRICS / SECTION V: MISCELLANEOUS DISORDERS 25 ABNORMAL ENDOCRINE TEST RESULTS DUE TO NONENDOCRINE CONDITIONS / TIMING AND PHYSIOLOGIC STATUS / NONENDOCRINE SYSTEMIC CONDITIONS / 26 AUTOIMMUNE ENDOCRINOPATHIES / THE ADAPTIVE IMMUNE SYSTEM IN HEALTH / AUTOIMMUNITY AND AUTOIMMUNE DISEASES / CLASSI?CATION AND RECOGNITION OF AUTOIMMUNE DISEASES / AUTOIMMUNE INSULIN RESISTANCE AND HYPOGLYCEMIA SYNDROMES / THYROID AUTOIMMUNITY / ADRENAL AUTOIMMUNITY / PARATHYROID AUTOIMMUNITY / GONADITIS / HYPOPHYSITIS / AUTOIMMUNE DI / NONENDOCRINE AUTOIMMUNITIES ASSOCIATED WITH IMMUNOENDOCRINOPATHIES / CONCLUDING REMARKS / 27 MULTIPLE ENDOCRINE NEOPLASIAS / NOEL K MACLAREN INTRODUCTION / ADRENAL ADENOMAS / THYROID ADENOMAS / PITUITARY ADENOMAS / PANCREATIC ADENOMAS / SUMMARY / 28 ENDOCRINE TUMORS IN CHILDREN / ADRENAL TUMORS / GONADAL TUMORS / TUMORS OF ENDOCRINE PANCREAS / 29 DISORDERS OF WATER HOMEOSTASIS / REGULATION OF FLUID BALANCE / CENTRAL DIABETES INSIPIDUS / NEPHROGENIC DIABETES INSIPIDUS / ADIPSIC HYPERNATREMIA / DIAGNOSTIC APPROACH TO AND THE DIFFERENTIAL DIAGNOSIS OF POLYURIA / HYPERNATREMIA / HYPONATREMIA / 30 ENDOCRINE DISORDERS AFTER CANCER THERAPY / HYPOTHALAMIC–PITUITARY AXIS AND GROWTH HORMONE DE?CIENCY / THYROID / GONADAL AND REPRODUCTIVE FUNCTION / OTHER ENDOCRINE AND METABOLIC COMPLICATIONS / GROWTH / PUBERTY AND GONADOTROPIN SECRETION / FOLLOW-UP AND MANAGEMENT / INTELLECTUAL AND NEUROPSYCHOLOGICAL RISKS / SECTION VI: SPECIAL CONSIDERATIONS AND RESOURCES 31 RADIATION TERRORISM / IONIZING RADIATION / DISPERSAL OF RADIOACTIVE SUBSTANCES WITH CONVENTIONAL EXPLOSIVES—DIRTY BOMBS / ATOMIC BOMBS / NUCLEAR POWER PLANTS / MANAGEMENT OF PREGNANT WOMEN AND CHILDREN / GLOBAL HEALTH EDUCATION ON RADIATION AND TERRORISM / 32 USING THE WEB TO OBTAIN INFORMATION ON GENETIC AND HORMONE DISORDERS / USING THE WEB TO OBTAIN INFORMATION FOR DYSMORPHIC PATIENTS / HOW TO GENERATE A DIFFERENTIAL DIAGNOSIS FOR A FAMILY HAVING UNUSUAL ENDOCRINE PROBLEMS / HOW TO OBTAIN INFORMATION ON A CASE OF ENDOCRINE NEOPLASIA / SELECTED WEB SITES ON GROWTH AND HORMONE DISORDERS / 33 HORMONAL DYNAMIC TESTS AND GENETIC TESTS USED IN PEDIATRIC ENDOCRINOLOGY / PRINCIPLES OF HORMONAL MEASUREMENTS / PRACTICAL CONSIDERATIONS / PRACTICAL PROTOCOLS FOR DYNAMIC TESTING IN CHILDREN / GENETIC TESTING / WORRISOME GROWTH INTRODUCTION GROWTH IS THE FUNDAMENTAL PHYSIOLOGIC PROCESS THAT CHARACTERIZES CHILDHOOD IT SHOULD BE CLOSELY MONITORED BY PEDIATRICIANS AND FAMILIES ALIKE AS A BENCHMARK OF A CHILD’S HEALTH SIMILARLY, SECULAR TRENDS IN GROWTH PATTERNS ARE FOLLOWED AS INDICATORS OF CHIL- DREN’S HEALTH ON A POPULATION LEVEL THE AMERICAN ACADEMY OF PEDIATRICS REITERATED THE IMPORTANCE OF GROWTH IN MARCH 12 ÐMONTHS PER YEARÞ NORMAL GROWTH VELOCITIES ARE DEPENDENT ON AGE AND PUBERTAL STAGE, AND ARE DETAILED LATER IN THE CHAPTER IF GROWTH VELOCITY IS ABNORMALLY SLOW FOR A CONSIDERABLE PERIOD OF TIME, IT MANIFESTS AS A FALL IN PERCENTILES WHEN PLOTTED ON THE GROWTH CHART THUS, THE TWO OTHER DE?NI- TIONS OF WORRISOME GROWTH ARE: (III) ABNORMALLY SLOW GROWTH VELOCITY, OR (IV) HEIGHT DROPPING ACROSS TWO MAJOR CENTILE LINES ON THE GROWTH CHART SHORT STATURE AND GROWTH FAILURE FREQUENTLY, BUT NOT ALWAYS, OCCUR TOGETHER FOR EXAMPLE, A HEALTHY CHILD OF SHORT PARENTS WILL HAVE SHORT STATURE BUT NOT GROWTH FAIL- URE; HE OR SHE WILL GROW AT NORMAL VELOCITY TOWARDS A LOWER GENETIC POTENTIAL CONVERSELY, A CHILD OF VERY TALL PARENTS CAN HAVE GROWTH FAILURE BUT STILL BE TALLER THAN THE CUT-OFF FOR SHORT STATURE OF THE GENERAL POPULATION GROWTH AND GROWTH DISORDERS