Endocrinology Adult and Pediatric: Neuroendocrinology and The Pituitary Gland E-Book (Endocrinology (deGroot))

Apply the latest advances in management of neuroendocrine and pituitary disorders with the Endocrinology: Adult and Pediatric: Neuroendocrinology and The Pituitary Gland eBook! Brought to you by the same expert endocrinologists responsible for the highly acclaimed two-volume Endocrinology clinical reference, this endocrinology eBook puts all of the newest latest know-how of the Pituitary Gland and Neuroendocrinology at your fingertips, instantly accessible on your favorite eReader - so you can offer your patients the best care . Stay abreast of the newest knowledge on neuroendocrinology and the pituitary gland, including our most recent understanding of the fundamental cellular and physiologic functions of the neuroendocrine system, mechanisms underlying clinical disorders, and approaches to managing patients harboring disorders of the hypothalamus and pituitary gland. Approach any subject either by specific gland or through a discussion of multi-hormonal integration of endocrine function, as led by the "master conductor of the endocrine orchestra," the pituitary gland. Gain a state-of-the-art understanding of comprehensive descriptors , integrating endocrine cell ontogeny, hormonal control of growth and maturation processes, and childhood and young adult pathophysiology with maturation and aging processes. Count on all the authority that has made Endocrinology, 6th Edition , edited by Drs. Jameson and DeGroot, the go-to medical reference for endocrinologists worldwide. Make the best clinical endocrinology decisions with an enhanced emphasis on evidence-based practice in conjunction with expert opinion. Consult this title on your favorite e-reader , conduct rapid searches, and adjust font sizes for optimal readability. Compatible with Kindle®, nook®, and other popular devices. Front cover Endocrinology Adult and Pediatric Online_Copyright page Senior Editors Contributors Preface Online_Table of contents 1 DEVELOPMENT OF THE PITUITARY Anatomy and Histology Pituitary Development ORIGIN ONTOGENY CELL LINEAGE DETERMINATION Transcription Factors and Pituitary Development PIT1 GENE Animal Model Related Diseases Mechanism PROP1 GENE Animal Model Related Diseases Mechanism HESX1 GENE Animal Model Related Diseases Mechanism LHX3 AND LHX4 GENES Animal Model Related Diseases Mechanism TBX19 GENE Animal Model Related Diseases Mechanism PITX1 AND PITX2 GENES Animal Model Related Diseases Mechanism OTHER TRANSCRIPTION FACTORS Signaling Pathways in Pituitary Development SONIC HEDGEHOGS FIBROBLAST GROWTH FACTORS TRANSFORMING GROWTH FACTORS AND BMPs NOTCHs WNTs INTERACTIONS BETWEEN DIFFERENT MORPHOGENIC FACTORS Opposing BMPs and FGFs Signaling Gradients Independent Hh and FGF Signaling in Pituitary Organogenesis OTHER POTENTIAL MORPHOGENETIC FACTORS Pituitary and Epigenetics PIT1 LOCUS—MULTIPLE ENHANCERS COORDINATE EXPRESSION OF THE GENE GROWTH HORMONE LOCUS—LCR, BOUNDARY, AND HISTONE CODE Adult Pituitary Stem Cells Summary Acknowledgments REFERENCES 2 PROLACTIN The Evolutionary Biology of Prolactin THE PROLACTIN FAMILY PLACENTAL LACTOGENS NONLACTOGENIC PROLACTIN RELATIVES EXTRAPITUITARY PROLACTIN The Biochemistry of Prolactin The Ontogeny and Physiology of Prolactin Secretion DEVELOPMENT OF LACTOTROPHS REGULATION OF PITUITARY PROLACTIN SYNTHESIS AND SECRETION DOPAMINE PROLACTIN-RELEASING FACTORS Pathophysiology of Prolactin Secretion PROLACTIN DEFICIENCY HYPERPROLACTINEMIA Prolactin Receptors and Signal Transduction RECEPTORS TYROSINE KINASE ACTIVATION TRANSCRIPTIONAL REGULATION The Physiology and Pathophysiology of Prolactin Actions in Mammals MAMMARY GLANDS FEMALE REPRODUCTIVE TISSUES MALE REPRODUCTIVE TISSUES ION BALANCE AND CALCIUM METABOLISM BRAIN AND BEHAVIOR HEMATOPOIESIS AND IMMUNOREGULATION METABOLISM Summary REFERENCES 3 ADRENOCORTICOTROPIC HORMONE History Pro-Opiomelanocortin Gene STRUCTURE OF THE POMC GENE POMC Transcripts The Pituitary Transcript T1 The Upstream Transcript T3 The Downstream Transcript T2 Regulatory Sites for Transcription EXPRESSION OF THE POMC GENE Expression in the Pituitary Expression in Other Tissues Expression in Pituitary Tumors Expression in Nonpituitary Tumors REGULATION OF POMC GENE EXPRESSION Regulation of the POMC Gene in the Pituitary Corticotropin-Releasing Hormone Stimulation of the POMC Gene Glucocorticoid Inhibition of the POMC Gene Stimulation of the POMC Gene by Arginine Vasopressin Leukemia Inhibitory Factor Stimulation of the POMC Gene Regulation of the POMC Gene in Other Tissues Brain Skin Placenta Regulation of the POMC Gene in Tumors Corticotropin-Releasing Hormone Regulation of the POMC Gene in Tumors Glucocorticoid Regulation of the POMC Gene in Tumors Adrenocorticotropic Hormone and Related Peptides STRUCTURE AND PROCESSING OF POMC AND RELATED PEPTIDES POMC ACTH α-Melanocyte-Stimulating Hormone CLIP N-Pro-opiomelanocortin γ-Melanocyte-Stimulating Hormone Joining Peptide β-Lipotropin β-Endorphin THE PROCESSING PATHWAY AND PROCESSING ENZYMES Processing N-Glycosylation and Phosphorylation Processing Enzymes PROCESSING IN DIFFERENT TISSUES Anterior Pituitary Intermediate Lobe Hypothalamus Other Tissues Pituitary Tumors Extrapituitary Tumors BIOLOGICAL ACTIVITY OF ACTH-RELATED PEPTIDES ACTH and Its Receptor ACTH Receptors and Signaling ACTH Effects on the Adrenal α-Melanocyte-Stimulating Peptide N-Pro-opiomelanocortin and Joining Peptide β-Lipotropin and β-Endorphin ACTH Precursors FACTORS REGULATING SECRETION OF ACTH AND RELATED PEPTIDES Glucocorticoids Fast Glucocorticoid Feedback Intermediate Glucocorticoid Feedback Slow Glucocorticoid Feedback Differential Glucocorticoid Regulation in Other Tissues Corticotropin-Releasing Hormone Vasopressin Other Regulatory Factors Cytokines and Growth Factors Interleukin 1 Interleukin 2 Interleukin 6 Leukemia Inhibitory Factor Integrated Control of ACTH Secretion Tier I Tier II Tier III Differential Regulation of POMC and ACTH MECHANISMS REGULATING SECRETION OF ACTH AND RELATED PEPTIDES Circadian Rhythmicity Pulsatility The Stress Response MEASUREMENT OF ACTH AND RELATED PEPTIDES ACTH and ACTH Precursors Other POMC-Derived Peptides REFERENCES 4 ENDOCRINE RHYTHMS, THE SLEEP-WAKE CYCLE, AND BIOLOGICAL CLOCKS Major Mechanisms Controlling 24-Hour Endocrine Rhythms CIRCADIAN RHYTHMICITY General Characteristics The Suprachiasmatic Nucleus: A Master Circadian Pacemaker Photic Entrainment of Circadian Rhythms Nonphotic Zeitgebers Sleep-Wake Regulation General Characteristics Neuroanatomic Basis of Sleep Regulation Interactions Between Circadian Rhythmicity and Sleep-Wake Homeostasis ULTRADIAN RHYTHMICITY Range of Ultradian Rhythms Properties and Clinical Implications of Pulsatile Hormonal Release IMPACT OF AGING ON MECHANISMS CONTROLLING ENDOCRINE RHYTHMS Methodologic Aspects of the Study of Endocrine Rhythms EXPERIMENTAL PROTOCOLS PROCEDURES TO QUANTIFY CIRCADIAN VARIATIONS PROCEDURES TO QUANTIFY PULSATILE HORMONAL SECRETION Endocrine Rhythms in Health and Disease PITUITARY AXES The Corticotropic Axis Normal Rhythms of Adrenocorticotropic Hormone and Adrenal Secretions Alterations in Disease States The Somatotropic Axis The 24 Hour Profile of Growth Hormone in Normal Subjects Alterations in Disease States The Lactotropic Axis The 24-Hour Profile of Prolactin in Normal Subjects Alterations in Disease States The Gonadotropic Axis Normal Diurnal Profiles of Gonadotropins and Sex Steroids Alterations in Disease States The Thyrotropic Axis The 24-Hour Profile of Thyrotropin in Normal Subjects Alterations in Disease States PARATHYROID HORMONE HYDROMINERAL HORMONES GLUCOSE TOLERANCE AND INSULIN SECRETION Diurnal and Ultradian Variations in Normal Subjects Alterations in Disease States HORMONES INVOLVED IN APPETITE REGULATION Leptin Ghrelin and Peptide YY Conditions of Altered Sleep and Circadian Rhythmicity SLEEP CURTAILMENT SLEEP DISORDERS Obstructive Sleep Apnea Other Sleep Disorders Circadian Misalignment Jet Lag Shift Work REFERENCES 5 HYPOTHALAMIC SYNDROMES Hypothalamic Disorders: Pathophysiologic Principles Manifestations of Hypothalamic Disease DISORDERS OF WATER METABOLISM Central Diabetes Insipidus Adipsic or Essential Hypernatremia Syndrome of Inappropriate Secretion of Antidiuretic Hormone Reset Osmostat Cerebral Salt Wasting DYSTHERMIA Hyperthermia Hypothermia Poikilothermia DISORDERS OF APPETITE CONTROL AND CALORIC BALANCE Hypothalamic Obesity Diencephalic Syndrome of Infancy Hypothalamic Cachexia in Adults Anorexia Nervosa Diencephalic Glycosuria SLEEP/WAKE CYCLE AND CIRCADIAN ABNORMALITIES ABNORMALITIES OF EMOTIONAL EXPRESSION OR BEHAVIOR DISORDERED CONTROL OF ANTERIOR PITUITARY FUNCTION Hyperfunction Syndromes Precocious Puberty Acromegaly Cushing’s Disease Hyperprolactinemia Hypofunction Syndromes Hypothalamic Hypogonadism Growth Hormone Deficiency Hypothalamic Hypoadrenalism Hypothalamic Hypothyroidism Specific Hypothalamic Disorders PRADER-WILLI SYNDROME BARDET-BIEDL AND RELATED SYNDROMES SEPTO-OPTIC PITUITARY DYSPLASIA HYPERPHAGIC SHORT STATURE (PSYCHOSOCIAL DWARFISM) PSEUDOCYESIS HYPOTHALAMIC HAMARTOMA SUPRASELLAR ARACHNOID CYST INFILTRATIVE DISORDERS HYPOTHALAMIC DYSFUNCTION AFTER BRAIN IRRADIATION TRAUMATIC BRAIN INJURY REFERENCES 6 HYPOPITUITARISM AND GROWTH HORMONE DEFICIENCY Epidemiology Mortality Causes PITUITARY AND HYPOTHALAMIC MASS LESIONS Pituitary Surgery Radiotherapy GENETIC CAUSES Combined Pituitary Hormone Deficit Isolated Pituitary Hormone Deficiency Isolated Growth Hormone Deficiency Isolated Gonadotropin Deficiency Isolated ACTH and TSH Deficiencies Traumatic Brain Injury Lymphocytic Hypophysitis Pituitary Apoplexy Granulomatous Diseases Hypopituitarism CLINICAL FEATURES Gonadotropin Deficiency Adrenocorticotropic Hormone Deficiency Thyroid-Stimulating Hormone Deficiency Antidiuretic Hormone Deficiency DIAGNOSIS AND ENDOCRINE EVALUATION Imaging Radiologic Phenotype of GH Deficiency Endocrine Evaluation Dynamic Testing Adult Gonadotropin Deficiency. Adrenocorticotropic Hormone Deficiency. Thyroid-Stimulating Hormone Deficiency. Antidiuretic Hormone Deficiency. MANAGEMENT Hormone Replacement in Hypopituitarism Gonadotropin Deficiency Estrogen Replacement. Androgen Replacement. Gonadotropin and Gonadotropin-Releasing Hormone Therapy. Adrenocorticotropic Hormone Replacement. Thyroid-Hormone Stimulating Hormone Deficiency. Antidiuretic Hormone Deficiency. Growth Hormone Deficiency in Adults CAUSES CLINICAL FEATURES Metabolism Body Composition Physical Performance Quality of Life DIAGNOSIS WHO TO TREAT BIOCHEMICAL DIAGNOSIS Provocative Test Biochemical Markers of GH Action GROWTH HORMONE REPLACEMENT Metabolism Body Composition Physical Performance Quality of Life Transition Age Patients TREATMENT Dosage Interaction Safety Contraindications Conclusions REFERENCES 7 ACROMEGALY Pathogenesis EXCESS GROWTH HORMONE SECRETION EXCESS GROWTH HORMONE–RELEASING HORMONE SECRETION ROLE OF THE HYPOTHALAMUS IN THE ETIOLOGY OF ACROMEGALY INTRINSIC PITUITARY LESIONS CANDIDATE GENES IN THE ETIOLOGY OF ACROMEGALY Inactivating Mutations Activating Mutations Familial Syndromes EPIDEMIOLOGY OF ACROMEGALY Diagnosis DOCUMENTING GROWTH-HORMONE HYPERSECRETION LOCALIZING THE SOURCE OF EXCESS GROWTH HORMONE Nonpituitary Acromegaly CLINICAL MANIFESTATIONS Acral Overgrowth Rheumatologic Features Skin and Soft Tissues Thyroid Cardiovascular Sleep Apnea Diabetes Gonadal Function Neoplasms LABORATORY FINDINGS MORTALITY Management TREATMENT GOALS SURGERY Side Effects PITUITARY IRRADIATION Side Effects PHARMACOLOGIC MANAGEMENT Somatostatin-Receptor Ligands Responses to Long-Term Depot SRIF Analog Preparations Side Effects Dopamine Agonists Adverse Events Growth Hormone–Receptor Antagonist Integrated Treatment Approach to the Management of Acromegaly PATIENTS WITH LIKELIHOOD OF GOOD SURGICAL OUTCOME PATIENTS WITH A POOR LIKELIHOOD OF SUCCESSFUL SURGICAL OUTCOME FOLLOW-UP GENERAL REFERENCES 8 CUSHING’S SYNDROME DEFINITION ETIOLOGY AND PATHOPHYSIOLOGY Cushing’s Syndrome Cushing’s Disease Ectopic Adrenocorticotropic Hormone Syndrome Ectopic Corticotropin-Releasing Hormone Secretion Primary Adrenal Disease PSEUDO-CUSHING’S STATES EPIDEMIOLOGY CLINICAL FEATURES PATHOLOGY CLINICAL SPECTRUM DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS ESTABLISHING THE DIAGNOSIS OF CUSHING’S SYNDROME Initial Screening Tests Urinary Free Cortisol Late-Night Salivary Cortisol Low-Dose Dexamethasone Suppression Tests Second-Line Tests The Dexamethasone-CRH Test Plasma Cortisol Circadian Rhythm Other Second-Line Tests DIFFERENTIAL DIAGNOSIS OF CUSHING’S SYNDROME Investigating Adrenocorticotropic Hormone–Independent Cushing’s Syndrome Differentiating Between Adrenocorticotropic Hormone–Dependent Causes of Cushing’s Syndrome Bilateral Inferior Petrosal Sinus Sampling High-Dose Dexamethasone Suppression Test Corticotropin-Releasing Hormone Stimulation Test Other Stimulation Tests Combined Test Strategies Imaging of the Adrenocorticotropin Hormone Source Strategy for Diagnosis and Differential Diagnosis of Cushing’s Syndrome TREATMENT SURGERY Preoperative Evaluation and Treatment Transsphenoidal Resection of Corticotropinoma Postoperative Evaluation and Management Adrenalectomy Surgery for Ectopic Adrenocorticotropic Hormone Syndrome RADIOTHERAPY Pituitary Conventional Radiotherapy Stereotactic Radiosurgery Interstitial Radiotherapy Other Tumors MEDICAL TREATMENT Agents Inhibiting Steroidogenesis Metyrapone Ketoconazole and Other Antifungals Mitotane Etomidate Glucocorticoid Receptor Antagonists Agents That Modulate ACTH Release Somatostatin Analogues Thiazolidinediones Potential Novel Medical Agents Special Clinical Scenarios CYCLIC CUSHING’S SYNDROME IATROGENIC AND FACTITIOUS CUSHING’S SYNDROME CHRONIC RENAL FAILURE PEDIATRIC CUSHING’S SYNDROME CUSHING’S SYNDROME IN PREGNANCY Prognosis REFERENCES 9 CLINICALLY NONFUNCTIONING SELLAR MASSES Natural History of a Pituitary or Parasellar Mass Types of Sellar Masses PITUITARY ADENOMAS PITUITARY HYPERPLASIA LYMPHOCYTIC HYPOPHYSITIS BENIGN TUMORS, NONPITUITARY Rathke’s Cleft and Other Cysts Craniopharyngiomas Meningiomas Pituicytomas MALIGNANT TUMORS Germ Cell Tumors (Ectopic Pinealomas) Chordomas Primary Lymphoma Metastatic Disease Pituitary Carcinoma Infiltrative and Granulomatous Diseases Abscess Vascular Abnormalities Etiology of Pituitary Adenomas Clinical Features NEUROLOGIC FEATURES Visual Abnormalities Oculomotor Abnormalities Other ENDOCRINOLOGIC FEATURES Hormonal Excess—Gonadotroph Adenomas Serum Concentrations of Gonadotropins and Their Subunits Clinical Syndromes Hormonal Excess—Other Pituitary Adenomas Hormonal Deficiencies Diagnosis UTILITY OF DIAGNOSING A CLINICALLY NONFUNCTIONING SELLAR MASS IMAGING OF THE SELLAR REGION ENDOCRINOLOGIC TESTS HISTOLOGIC EVALUATION APPROACH TO THE PATIENT WITH A SELLAR MASS Treatment SURGERY Surgical Approaches Efficacy of Surgery Complications of Surgery Evaluation of the Results of Surgery RADIATION Techniques of Radiation Efficacy of Radiation Complications of Radiation Management of Patients After Radiation PHARMACOLOGIC TREATMENT OBSERVATION REFERENCES 10 TSH-PRODUCING ADENOMAS Epidemiology Pathology and Etiopathogenesis Clinical Features Biochemical Findings TSH AND THYROID HORMONE LEVELS GLYCOPROTEIN HORMONE α SUBUNIT PARAMETERS EVALUATING PERIPHERAL THYROID HORMONE ACTION Dynamic Testing Imaging Studies and Localization Differential Diagnosis Treatment and Outcome PITUITARY SURGERY AND RADIATION THERAPY MEDICAL TREATMENT Criteria of Cure and Follow-Up Conclusions Acknowledgment REFERENCES 11 DISORDERS OF PROLACTIN SECRETION AND PROLACTINOMAS History Epidemiology Pathogenesis Pathology ACIDOPHIL STEM CELL ADENOMA NONTUMORAL LESIONS ASSOCIATED WITH HYPERPROLACTINEMIA PITUITARY PROLACTIN-SECRETING CARCINOMAS Differential Diagnosis of Hyperprolactinemia PHYSIOLOGIC HYPERPROLACTINEMIA PHARMACOLOGIC HYPERPROLACTINEMIA PATHOLOGIC HYPERPROLACTINEMIA Diagnosis of Prolactinomas CLINICAL FEATURES LABORATORY EVALUATION IMAGING Treatment SURGICAL THERAPY MEDICAL THERAPY Bromocriptine Pergolide Quinagolide (CV 205-502) Cabergoline RADIOTHERAPY THERAPEUTIC PERSPECTIVES PROLACTINOMAS AND PREGNANCY Pregnancy and Other Dopamine Agonist Drugs Follow-Up After Delivery TREATMENT PLANNING AND FOLLOW-UP REFERENCES 12 PITUITARY SURGERY Historical Background Surgical Anatomy Surgery TRANSSPHENOIDAL APPROACHES Microsurgical Transsphenoidal Approaches Microsurgical Transnasal Transseptal Transsphenoidal Approach Microsurgical Sublabial Transseptal Transsphenoidal Approach Microsurgical Endonasal Transsphenoidal Approach Endoscopic Endonasal Transsphenoidal Approach Extended Endoscopic Endonasal Approach to the Suprasellar Area TRANSCRANIAL APPROACHES RADIOSURGERY Complications Acknowledgments REFERENCES 13 EVALUATION AND MANAGEMENT OF CHILDHOOD HYPOTHALAMIC AND PITUITARY TUMORS Epidemiology Classification Symptoms and Signs ENDOCRINE DYSFUNCTION Diagnosis Therapy GENERAL PRINCIPLES OF TREATMENT PERIOPERATIVE MANAGEMENT SURGICAL THERAPY CHEMOTHERAPY RADIOTHERAPY Sequelae of Treatment Treatment of Specific Tumors OPTIC CHIASMATIC–HYPOTHALAMIC GLIOMAS CYSTIC SELLA TUMORS PINEAL TUMORS REFERENCES 14 VASOPRESSIN, DIABETES INSIPIDUS, AND THE SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION Vasopressin SYNTHESIS AND SECRETION CELLULAR ACTION OF VASOPRESSIN The V1 Receptor The V2 Receptor The V3 Receptor Regulation of Vasopressin Release OSMOREGULATION OF VASOPRESSIN RELEASE BAROREGULATION OF VASOPRESSIN RELEASE OTHER MECHANISMS REGULATING VASOPRESSIN RELEASE Diabetes Insipidus HYPOTHALAMIC DIABETES INSIPIDUS NEPHROGENIC DIABETES INSIPIDUS DIPSOGENIC DIABETES INSIPIDUS INVESTIGATION OF DIABETES INSIPIDUS ADIPSIC DIABETES INSIPIDUS TREATMENT FOR DIABETES INSIPIDUS The Syndrome of Inappropriate Antidiuretic Hormone INTRODUCTION CAUSES OF SIADH PATHOPHYSIOLOGY OF SIADH DIAGNOSIS OF SIADH DIFFERENTIAL DIAGNOSIS OF SIADH Glucocorticoid Deficiency Hypothyroidism TREATMENT FOR SIADH Factors Affecting Therapy Treatment for Chronic Hyponatremia REFERENCES 15 THE PINEAL GLAND AND MELATONIN Pineal Gland NEURAL INNERVATION OF THE PINEAL GLAND Melatonin SYNTHESIS AND SECRETION OF MELATONIN Melatonin Receptors Melatonin Metabolism Actions of Endogenous and Exogenous Melatonin SLEEP JET LAG REPRODUCTION TEMPERATURE BLOOD PRESSURE IMMUNE SYSTEM AND CANCER ANTIOXIDANT AND ANTI-AGING PSYCHIATRIC DISORDERS Lesions of the Pineal Gland and Pineal Region PINEAL GLAND CYSTS TUMORS IN THE PINEAL GLAND REGION Meningiomas Pineal Parenchymal Tumors Pineocytoma Pineoblastoma Intermediate Pineal Parenchymal Tumors Germ Cell Tumors Clinical Presentation for All Tumors in the Pineal Region IMAGING Magnetic Resonance Imaging Computer Axial Tomography STAGING WORKUP AND HISTOLOGIC DIAGNOSIS General Treatment Remarks Specific Treatments Pineocytoma Pineoblastoma Germinomas Teratomas Nongerminomatous Germ Cell Tumors Trilateral Retinoblastoma REFERENCES 16 REGULATION OF GROWTH HORMONE AND ACTION (SECRETAGOGUES) Growth Hormone GH ACTIVITIES STRUCTURE OF GH STRUCTURE/FUNCTION STUDIES OF GH THE THIRD α HELIX OF GH GH ANTAGONISTS CO-CRYSTALLIZATION OF GH WITH THE GHR Growth Hormone Receptor GHR AND GHBP GH/GHR INTERACTION CLINICAL MANISFESTATIONS OF MUTATIONS IN THE GHR GH-Induced Signal Transduction JANUS KINASE ACTIVATION SIGNAL TRANSDUCERS AND ACTIVATORS OF THE TRANSCRIPTION SIGNALING PATHWAY MITOGEN-ACTIVATED PROTEIN KINASE SIGNALING PATHWAY INSULIN RECEPTOR SUBSTRATE/PI3K-AKT SIGNALING PATHWAY PROTEIN KINASE C SIGNALING PATHWAY SUPPRESSORS OF CYTOKINE SIGNALING, PROTEIN TYROSINE PHOSPHATASES, AND SRC KINASES GHRH, Ghrelin, and GH Secretagogues Growth Hormone–Releasing Hormone HISTORY MOLECULAR AND CELLULAR BIOLOGY GHRH Peptide Gene and mRNA Tissue Distribution GHRH RECEPTOR GHRH Receptor mRNA and Gene GHRH INTRACELLULAR SIGNALING cAMP Metabolism Phospholipids Mitogenic Signaling GH mRNA and Release Dynamics in Culture ANIMAL STUDIES GHRH Release GHRH Effects on the GH Axis GHRH Effects on Functions Outside of the GH Axis Circulating GHRH in Humans GHRH Levels in Acromegaly Eutopic GHRH Secretion GHRH Levels in GH-Deficient Children GHRH AS A DIAGNOSTIC AGENT Administration of GHRH to Normal Individuals The GHRH Test The GHRH Test in Children With Short Stature Normal Hypothalamic-Pituitary-GH Axis. GH Deficiency. GHRH and the Diagnosis of GH Deficiency in Adults Limitations of the GHRH Test Tests Utilizing GHRH in Combination With Other Agents GHRH THERAPY IN GH-DEFICIENT CHILDREN GHRH Given by Pump GHRH Given sc Twice a Day GHRH Given sc Once a Day Which Children Should be Considered for GHRH Therapy? Adverse Effects GHRH TREATMENT IN ADULTS Ghrelin and Growth Hormone Secretagogues (GHS) GHRELIN STRUCTURE ASSAYS FOR GHRELIN Sites of Ghrelin Synthesis REGULATION OF GHRELIN PHYSIOLOGY AND MOLECULAR BIOLOGY SITES OF ACTION GHS RECEPTOR Regulation of the GHS Receptor Evidence for Alternative Ligands and Receptor Subtypes EFFECTS OF GHRELIN AND GHSs GH-Related Effects Other Hormone-Related Effects Feeding Effect Other Effects of Ghrelin GHRELIN LEVELS IN PATHOLOGIC CONDITIONS Abnormal Body Weight Diabetes Mellitus and Insulin Resistance Prader-Willi Syndrome Acromegaly and Growth Hormone Deficiency Hyperthyroidism Renal Disease MODELS OF GHRELIN OR GHRELIN RECEPTOR DEFICIENCY CLINICAL IMPLICATIONS OF GHRELIN AND GHS Growth Hormone Secretagogues GHS ACTIONS IN HEALTHY SUBJECTS GHSs AND THE DIAGNOSIS OF GH DEFICIENCY THE GHRH AND GHS TEST IN DIFFICULT DIAGNOSTIC SITUATIONS Obesity Syndromes of Glucocorticoid Excess THERAPEUTIC POTENTIAL OF GHSs Therapeutic Potential of GHSs in Children Therapeutic Potential of GHSs in Adults Summary REFERENCES 17 INSULIN-LIKE GROWTH FACTOR-1 AND ITS BINDING PROTEINS IGF-1 Gene and Protein Structures IGF-1 Receptor Receptor-Mediated Signal Transduction IGF-2 Mannose-6 Phosphate Receptor IGF-Binding Proteins SPECIFIC PROPERTIES OF EACH FORM OF IGFBP CONTROL OF IGF-1 CONCENTRATIONS IN SERUM CONTROL OF IGFBP CONCENTRATIONS IN BLOOD AND EXTRACELLULAR FLUIDS CONTROL OF IGF-1 SYNTHESIS IN TISSUES Cartilage and Bone Reproductive Tract Neural Tissue Skeletal Muscle Liver Development IGF-1 Expression in Kidney CONTROL OF IGFBP CONCENTRATIONS IN TISSUES Actions of the IGFs IGF-1 ACTIONS IN VITRO Cell Cycle Progression EFFECTS OF IGF-1 ON THE PROLIFERATION OF DIFFERENT TYPES OF CELLS Cartilage Bone Skin Skeletal Muscle Smooth Muscle Nervous System Other Cell Types EFFECTS ON CELL DEATH EFFECTS ON CELLULAR DIFFERENTIATION EFFECTS ON SPECIFIC CELLULAR FUNCTIONS ROLE OF IGF-1 IN MALIGNANT TUMORS Control of IGF-1 Actions in Cells and Tissues by IGFBPs VARIABLES THAT REGULATE IGFBP AFFINITY Proteolysis IGFBP Phosphorylation Adherence to Cell Surface, Extracellular Matrix, and Glycosaminoglycans EFFECTS OF SPECIFIC FORMS OF IGFBPs ON IGF-1 ACTIONS IGFBP-1 IGFBP-2 IGFBP-3 IGF-Independent Effects of IGFBP-3 IGFBP-4 IGFBP-5 IGFBP-6 Actions of IGF-1 in vivo Modulation of in-vivo Actions by IGFBPs Transgenic Animal and Gene-Targeting Studies Autocrine/Paracrine Regulation of IGF-1-Mediated Growth Effects of IGF-1 in Humans BONE METABOLISM OTHER EFFECTS OF IGF-1 IGF-1 in Diabetes Growth Hormone Insensitivity Syndromes REFERENCES 18 SOMATIC GROWTH AND MATURATION Determinants of Normal Growth CELLULAR GROWTH SOMATIC GROWTH Prenatal Growth Postnatal Growth Patterns of Normal Somatic Growth INTRAUTERINE GROWTH POSTNATAL GROWTH CATCH-UP AND CATCH-DOWN GROWTH AND COMPENSATORY GROWTH SKELETAL MATURATION: BONE AGE IN PREDICTION OF ADULT HEIGHT AND PUBERTAL MILESTONES Growth Disorders SHORT STATURE Causes of Short Stature (Table 18-3) Genetic and Familial Conditions Familial Variants. Skeletal Dysplasias. Chromosomal Abnormalities, Monogenic Disorders, and Syndromes Turner’s Syndrome. Noonan’s Syndrome. Prader-Willi Syndrome. 18q Deletions. Down Syndrome. Intrauterine Growth Retardation and Small for Gestational Age Undernutrition and Chronic Nonendocrine Disease. Endocrine Disorders GH Deficiency GH Insensitivity Syndromes Hypothyroidism Glucocorticoid Excess Pseudohypoparathyroidism Idiopathic Short Stature (ISS) Differential Diagnosis of Short Stature by Growth Pattern Diagnostic Evaluation Management TALL STATURE Causes of Tall Stature Differential Diagnosis of Tall Stature by Growth Pattern Diagnostic Evaluation Management REFERENCES 19 GROWTH HORMONE DEFICIENCY IN CHILDREN History Epidemiology Pathogenesis GENETIC AND STRUCTURAL ABNORMALITIES Pituitary Development Disorders of Pituitary and Extra-Pituitary Development in Humans Growth Hormone–Releasing Hormone and Its Receptor Somatotroph Development GH1 Gene Bioinactive Growth Hormone Molecule Structural Abnormalities ACQUIRED DEFECTS Destructive Lesions of the Hypothalamus and Pituitary Tumors Irradiation of the Central Nervous System Traumatic Brain Injury Infiltrative and Inflammatory Disorders Vascular Lesions Psychosocial Dwarfism Clinical Features THE HYPOTHALAMO-PITUITARY-SOMATOTROPH AXIS NEONATAL PRESENTATION INFANT AND CHILDHOOD YEARS Diagnosis of Growth Hormone Deficiency in Childhood GUIDANCE DERIVED FROM CLINICAL ASSESSMENT Neonatal Period Infancy and Childhood PRINCIPLES OF TESTING Pre- and Post-test Probability Multiple Tests DIAGNOSIS OF GROWTH HORMONE DEFICIENCY PRACTICAL APPROACH TO DIAGNOSTIC EVALUATION Treatment GROWTH HORMONE Dose Studies Frequency of Administration Prediction Models Height Outcomes and the Influence of Puberty Adverse Effects of Human Growth Hormone End-Points of Therapy GROWTH HORMONE–RELEASING HORMONE GROWTH HORMONE–RELEASING PEPTIDES AND NONPEPTIDYL GROWTH HORMONE SECRETAGOGUES TRANSITION TO ADULT CARE REFERENCES Index A B C D E F G H I J K L M N O P Q R S T U V W Y Z Blank Page These volumes have been considered the definitive source in its field for decades. Now this landmark reference has been exhaustively updated to bring you the latest clinical guidance on all aspects of diagnosis and treatment for the full range of endocrine and metabolism disorders, including new information on diabetes, obesity, MEN I and II, disorders of sex determination, and pituitary tumors. Entirely new chapters on Lipodystrophy Syndromes, Lipoprotein Metabolism, and Genetic Disorders of Phosphate Homeostasis keep you well informed on today's hot topics. You'll benefit from unique, global perspectives on adult and pediatric endocrinology prepared by an international team of renowned authorities