The Human Hypothalamus: Neuroendocrine Disorders

Description

The Human Hypothalamus: Neuroendocrine Disorders, Volume 181 in the Handbook of Clinical Neurology series, provides comprehensive summaries of recent research on the brain and nervous system as they relate to clinical neurology. This volume summarizes the role of the hypothalamus in neuroendocrine disorders, identifying the mechanism of action, disorder etiology, and best practices for assessment and treatment. Disorders covered include pituitary hypothalamic disorders of development and growth, hypothalamic tumor related disorders, hypothalamic autoimmune disorders and infection, disorders of vasopressin, water and sodium homeostasis, eating disorders, and gonadotropic hormone regulation disorders. Front Cover The Human Hypothalamus: Neuroendocrine Disorders Copyright Handbook of Clinical Neurology 3rd Series Foreword Preface The HCN volumes on the Human Hypothalamus The hypothalamus: Arbitrary borders References Contributors Contents Contents of related volumes Chapter 1: Introduction: The human hypothalamus and neuroendocrine disorders Section 15#: Structural Disorders of the Hypothalamo–pituitary Region Section 16: Tumors of the Hypothalamus Section 17: Neuroimmunological Disorders Section 18: Drinking Disorders Section 19: Eating Disorders Section 20: Reproduction and Sexual Behavior References Section 15: Structural disorders of the hypothalamo-pituitary region Chapter 2: Pituitary stalk interruption syndrome Introduction Epidemiology Magnetic Resonance Imaging findings Clinical Manifestations Hormonal Profile and Evolution of Hormone Deficiencies Treatment Pathogenesis of Pituitary Stalk Interruption Syndrome Genetics of Pituitary Stalk Interruption Syndrome Genes involved in pituitary organogenesis Genes involved in neural development Holoprosencephaly (HPE)-related genes Cilia-related genes PSIS associated with microdeletions or duplications Digenic and polygenic inheritance and the application of next generation sequencing Environmental Factors and PSIS Conclusions and Perspectives References Chapter 3: Empty sella syndrome: Multiple endocrine disorders Introduction Classification Epidemiology Pathogenesis of Empty Sella Presenting Clinical Manifestations Endocrine symptoms Neurological and ophthalmological symptoms Diagnosis Endocrinological assessment Ophthalmological assessment Radiological assessment Differential Diagnosis Treatment Strategies Hypopituitarism Intracranial hypertension Follow-Up Prognosis Conclusion Acknowledgments Declaration in interest Funding References Chapter 4: Pituitary dysfunction after aneurysmal subarachnoidal hemorrhage Introduction Epidemiology Treatment and Management of aSAH Neuroendocrine Dysfunction in aSAH Patients Neuroendocrine Dysfunction in the Acute Phase after aSAH ACTH in the acute phase after aSAH FSH/LH in the acute phase after aSAH GH in the acute phase after aSAH TSH in the acute phase after aSAH Overall neuroendocrine dysfunction in the acute phase after aSAH Neuroendocrine Dysfunction in the Chronic Phase after aSAH ACTH in the chronic phase after aSAH FSH/LH in the chronic phase after aSAH GH in the chronic phase after aSAH TSH in the chronic phase after aSAH Overall neuroendocrine dysfunction in the chronic phase after aSAH Neuroendocrine Dysfunction in aSAH Patients: Changes from the Acute to the Chronic Phase Conclusions References Chapter 5: Septo-optic dysplasia Introduction Etiology and Pathogenesis Development of the Forebrain and Pituitary Gland Neuropathological Studies Epidemiology Clinical Presentation Visual disturbances Endocrinology disturbances Neurologic aspects Diagnostic Stage Ophthalmologic assessment Neuroradiology investigation Endocrinology workup Additional investigations Clinical and Surgical Management Prognosis and Outcome Conclusion Acknowledgments Disclosure References Section 16: Tumors of the hypothalamus Chapter 6: Hypothalamic hormone-producing tumors Introduction Tumor Classification, Clinical, and Morphological Features Therapeutic Approaches References Chapter 7: Craniopharyngiomas primarily affecting the hypothalamus Introduction1 Craniopharyngioma: A pituitary, suprasellar or hypothalamic tumor? Craniopharyngiomas primarily affecting the hypothalamus: Definition, anatomical relationships, and embryological origin Hypothalamus involvement by craniopharyngiomas: Historical insights Hypothalamus-referenced topographical classification of craniopharyngiomas Hypothalamic dysfunction caused by CPs: Infundibulo-tuberal syndrome versus hypothalamic syndrome Infundibulo-tuberal syndrome Hypothalamic syndrome Fröhlich's syndrome: Pathogenesis of sexual immaturity Hypothalamic obesity in craniopharyngioma patients Pathogenesis of hypothalamic obesity in Hy-CP patients: The role of astrogliosis Diurnal somnolence in CP patients Emotional, cognitive, and psychiatric disturbances: Clinical landmarks of Hy-CPs MRI assessment of CP-hypothalamus relationships: The usefulness of the mamillary body angle Surgical risk: The formidable problem of CP-hypothalamic adhesions Surgical strategies for CPs primarily affecting the hypothalamus Complications and sequelae derived from surgically caused hypothalamic injury Radiosurgery, proton beam therapy, and chemotherapy for the treatment of CPs involving the hypothalamus Genetic profile and targeted therapy for papillary CPs involving the hypothalamus Conclusions Acknowledgments Compliance with ethical standards Sources of funding Disclosure of potential conflict of interest Abbreviations References Section 17: Neuroimmunological disorders Chapter 8: The stress-axis in multiple sclerosis: Clinical, cellular, and molecular aspects Introduction The Stress-Axis in MS Determinants of Stress-Axis Responsiveness Neurodegeneration vs inflammation Sex and subtype-specific differences Differences in glucocorticoid receptor genotype Pathological, Cellular, and Molecular Effects of Stress-Axis Responsiveness Clinical Correlates of HPA Axis Activity in MS Outlook References Chapter 9: Neuroendocrine manifestations of Langerhans cell histiocytosis Introduction Epidemiology Diagnostic Criteria Neuroendocrine Manifestations of LCH Anterior pituitary hormones deficiency Posterior pituitary hormones deficiency Hypothalamic involvement Others sites of involvement Management of LCH Chemotherapy Management of neuroendocrine manifestations in LCH Follow-up of LCH patients Conclusions References Chapter 10: Neuroendocrine manifestations of Erdheim-Chester disease Introduction Manifestations of Hypothalamus, Pituitary Stalk, and/or Pituitary Gland Lesions Manifestations of Posterior Pituitary Hormone Deficiencies (Arginine Vasopressin and/or Oxytocin Deficiencies) Manifestations of Anterior Pituitary Hormone Deficiencies ACTH Deficiency (Hypothalamic-Pituitary-Adrenal Axis) TSH Deficiency (Hypothalamic-Pituitary-Thyroid Axis) GH Deficiency Gonadotropin Deficiency (Hypothalamic-Pituitary-Gonadal Axis) Hyperprolactinemia PRL Deficiency Conclusions References Chapter 11: Hypothalamitis and pituitary atrophy Introduction Pathogenesis Clinical Presentation Diagnosis Neuroradiological features Differential Diagnosis Treatment Prognosis Conclusion References Chapter 12: Narcolepsy Type I as an autoimmune disorder Narcolepsy Type 1 Genetic Associations in Narcolepsy Type 1 Environmental Factors Linked to Disease Development Pathologic Findings Postmortem in Narcolepsy Type 1 Immune System Chances in Narcolepsy Type 1 Patients Circulating cytokines Autoantibodies T cells Animal Models of Narcolepsy Type 1 Is Narcolepsy Type 1 an Autoimmune Disease? References Chapter 13: Neuromyelitis optica, aquaporin-4 antibodies, and neuroendocrine disorders Neuromyelitis Optica Spectrum Disorders Introduction Epidemiological, clinical, and radiological features of AQP4-IgG NMOSD Circumventricular Organs and the Hypothalamus as Target of Aquaporin-4 Autoimmunity Aquaporin-4 expression and function in the hypothalamus The Spectrum of Neuroendocrine Disorders in Neuromyelitis Optica Syndrome of inappropriate antidiuresis Sleep disorders Other endocrinopathies caused by hypothalamic involvement in NMOSD Treatment of NMOSD References Chapter 14: Antibodies against the pituitary and hypothalamus in boxers Traumatic Brain Injury: Epidemiology, Causes, and Outcomes TBI and Neuroendocrine Abnormalities Autoimmunity and Hypothalamo-Pituitary Dysfunction Boxing and Autoimmunity Acknowledgment References Chapter 15: Autoimmune diabetes insipidus Introduction1 Autoantibody Studies Vasopressin cell antibodies in the diagnosis of autoimmune DI Autoantibodies to rabphilin-3A, a major target autoantigen in autoimmune DI Comparison of cytoplasmic AVPcAb and autoantibodies to rabphilin-3A Association of autoimmune DI with endocrine autoimmune diseases AVPcAb and antibodies to rabphilin-3A in normal individuals without diabetes insipidus Imaging: MRI of the brain and the pituitary gland, and FDG-PET Relevance of AVPcAb and pituitary stalk thickening for the diagnosis of autoimmune DI Immunohistochemical studies The clinical picture of autoimmune DI Association of lymphocytic infundibuloneurohypophysitis with lymphocytic anterior hypophysitis Natural course of autoimmune DI/LINH Treatment of autoimmune CDI/LINH Autoimmune DI following therapy with immune checkpoint inhibitors Potential pitfalls in the diagnosis of autoimmune DI Summary and outlook Abbreviations References Section 18: Drinking disorders Chapter 16: Neuroimaging of central diabetes insipidus Introduction Neuroanatomy and Neurophysiology of the Hypothalamic-Neurohypophyseal Axis Imaging of the hypothalamic neurohypophyseal axis and MRI protocol Normal MRI appearances of the hypothalamic-neurohypophyseal axis MRI findings in CDI Causes of Central Diabetes Insipidus Neoplastic Rathke's cleft cyst Craniopharyngioma Hypothalamic or tuber cinereum hamartoma Germinoma Hypothalamic-chiasmatic glioma Meningioma Lymphoma Leukemia Teratoma Pituitary adenoma Metastases Traumatic Postoperative sella Head injury Hereditary CDI and Brain Malformations Autoimmune Lymphocytic hypophysitis/lymphocytic infundibulo-neurohypophysitis IgG4 hypophysitis Immunotherapy-related hypophysitis Inflammatory/granulomatous disorders Neurosarcoidosis Granulomatosis with polyangiitis (Wegener's granulomatosis) Eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome) Langerhans cell histiocytosis Meningitis Tuberculosis Other Hypoxic ischemic injuries Discussion Summary and future directions References Chapter 17: Differential diagnosis of familial diabetes insipidus History Physiology Pathophysiology Familial DI Differential Diagnosis of Familial DI Conclusions References Chapter 18: The vasopressin-aquaporin-2 pathway syndromes Defective Vasopressin-AQP2 Pathway in Nephrogenic Diabetes Insipidus (NDI) Altered Vasopressin-AQP2 Pathway in the Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) Altered Vasopressin-AQP2 Pathway in Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD) Constant Tonic Action of Vasopressin-AQP2 Pathway in Polycystic Kidney Disease References Chapter 19: Adipsic diabetes insipidus Introduction Physiology of Arginine Vasopressin and Thirst Etiology of Adipsic Diabetes Insipidus Anterior communicating artery aneurysm Craniopharyngioma Other tumors Infiltrative diseases Other causes Associated Diseases Sleep apnea Obesity Venous thromboembolism Seizures Temperature dysregulation Rhabdomyolysis and acute kidney injury Infections Management of Adipsic Diabetes Insipidus Prognosis and Future Directions References Chapter 20: Animal models for diabetes insipidus Determinants of the Intake and Excretion of Water and Mineral Salts Diabetes Insipidus: Characteristics and Types Animal Models of Central and Nephrogenic DI Animal models of central diabetes insipidus Hereditary CDI Acquired CDI Neurohypophysectomy, pituitary stalk compression, and pituitary stalk electrolytic lesion (PSEL) Hypophysectomy Mediobasal hypothalamic lesion Animal models of NDI Hereditary NDI Acquired NDI From Animal Models to Emerging Human Therapies for DI Acknowledgments Conflicts of interest References Chapter 21: Nocturnal enuresis in children: The role of arginine-vasopressin Introduction Nocturnal Enuresis as a Complex Condition: Elements of Pathophysiology The Concept of Nocturnal Polyuria in Nocturnal Enuresis Circadian Rhythms, Arginine-Vasopressin, and Nocturnal Polyuria Nocturnal Polyuria Unrelated to AVP Antidiuretic Treatment of Nocturnal Enuresis With Vasopressin Analogues The Refractory Patient AVP and the Genetics of Nocturnal Enuresis Conclusions and Future Perspectives References Section 19: Eating disorders Chapter 22: Monogenic human obesity syndromes Introduction Leptin-A Peripheral Hormone that Acts on Circuits in the Hypothalamus to Regulate Weight Homozygous Mutations in the Genes Encoding Leptin and the Leptin Receptor Genetic Disorders that Disrupt Melanocortin Signaling Semaphorin 3 Signaling Affects the Development of POMC Neurons SRC-1 and PHIP Modulate the Transcription of POMC SIM1 and OTP Shape the Development of the PVN BDNF, TrkB Affect Weight, Memory, and Behavior SH2B1 Links Weight Regulation and Aggression Conclusions References Chapter 23: Hypothalamic microinflammation Introduction Hypothalamic Microinflammation Discovered in Animals Hypothalamic Microinflammation: Human Relevance A Few Inducers of Hypothalamic Microinflammation Hypothalamic Microinflammation in Chronic Overnutrition Hypothalamic Microinflammation in Early Aging Hypothalamic Microinflammation: A Basis for Obesity Hypothalamic Microinflammation: A Basis for Diabetes Hypothalamic Microinflammation: A Basis for Hypertension Hypothalamic Microinflammation: A Basis for Aging Concluding Remarks References Chapter 24: Glucose and fat sensing in the human hypothalamus Introduction Hypothalamic Sensing of Glucose and Fats Glucose sensing Dietary glucose, sensing of and response to glucose ingestion Fat sensing Dietary fats, sensing of and response to fat ingestion Interaction between glucose and fat sensing Disrupted glucose and fat sensing Disrupted energy balance, obesity, and diabetes type 2 Structural or genetic disorders affecting the hypothalamus Summary, Implications, and Future Perspectives Summary and implications Future perspectives Concluding Remarks References Chapter 25: Hypothalamus and neuroendocrine diseases: The use of human-induced pluripotent stem cells for disease modeling Introduction11Abbreviations used in the chapter are listed at the end of the chapter before References section. Development of Human Neuroendocrine Hypothalamus Differentiation of Human-Induced Pluripotent Stem Cell Into Hypothalamic Neurons Modeling Neuroendocrine Diseases (Obesity) in a Dish Using hiPSC-Derived Hypothalamic Neurons References Chapter 26: Prader-Willi syndrome: Hormone therapies Introduction Genetics PWS phenotype: A neurodevelopmental endocrine/metabolism trajectory Causes of endocrine dysfunction Endocrine dysfunction GH status Thyroid hormones Gonadotropins and sex steroids Premature adrenarche and precocious puberty Impaired OXT pathways Abnormal ghrelin system Endocrine Treatments Recombinant human GH treatment Sustained positive effects of rhGH treatment in children Long-term outcome of rhGH treatment A transition period from adolescence to young adulthood Safety and tolerance Treatment of hypothyroidism Treatment of hypogonadism and delayed or incomplete puberty Treatment of premature adrenarche and precocious puberty Oxytocin and oxytocin analogue treatments Therapeutic perspectives targeting the ghrelin system in PWS Conclusions References Chapter 27: Transcriptomics of the Prader-Willi syndrome hypothalamus Introduction Prader-Willi syndrome Hypothalamus in PWS Imaging studies Histopathological findings in PWS Transcriptomics Analysis in Prader-Willi Syndrome Overview of gene expression changes in PWS Neuronal vs glial cell populations in the PWS hypothalamus Pathway analysis of PWS: Downregulated pathways Brain-derived neurotrophic factor deficiency in PWS hypothalamus Pathway analysis of PWS: Upregulated pathways Satiety pathways Transcriptomic parallels with other brain transcription signatures Conclusions and future research directions Funding References Chapter 28: Disorders of hypothalamic function: Insights from Prader-Willi syndrome and the effects of craniopharyngioma Introduction Craniopharyngioma Prader-Willi Syndrome Comparisons Between Hypothalamic CP and PWS Weight gain and obesity Appetite hormones Hypothyroidism (TSH dysfunction) Leptin Growth hormone Bone density Sex hormones and hypogonadism Sleep disorders Temperature Memory and IQ Socialization and behavior Conclusions References Chapter 29: Animal models for Prader-Willi syndrome Introduction Phenoptypes in Mouse Models Survival Growth retardation Hyperphagia, metabolism, and body composition Sexual maturation Cognition Sensory and motoric function Circadian rhythms Conclusion References Chapter 30: Is there a hypothalamic basis for anorexia nervosa? Introduction11Abbreviations used in the chapter are listed at the end of the chapter before References section. Genetics and Epigenetics of Anorexia Nervosa Structural and Functional Imaging and Brain Connectivity in Anorexia Nervosa Hypothalamic Control of Energy Homeostasis/Peripheral and Hypothalamic Adaptations in Anorexia Nervosa Peripheral Sensors of Nutritional and Energy Status Acting in the Hypothalamus Ghrelin: A sensor of undernutrition with neuroendocrine and metabolic activities Leptin, a long-term sensor of energy stores that regulates energy balance and gonadotropic axis Hypothalamic and Neuroendocrine-Related Agents in Anorexia Nervosa Anorexigenic neuropeptides/neuromediators α-Melanocyte-stimulating hormone Corticotropin-releasing hormone Brain-derived neurotrophic factor Neuropeptide B, neuropeptide W Peptide YY Thyrotropin-releasing hormone Oxytocin Vasopressin Kisspeptin Orexigenic neuropeptides/neuromediators Neuropeptide Y Agouti-related protein Orexin 26RFa Galanin Somatostatin Vaspin Neuroendocrine/Hypothalamic Adaptations in Animal Models of Undernutrition Conclusion References Section 20: Reproduction, olfaction and sexual behavior Chapter 31: Sexual differentiation of the human hypothalamus: Relationship to gender identity and sexual orientation Introduction: Programming of the Brain Gender-Based Differences in Behavior Mechanisms Involved in Sexual Differentiation of the Brain Hormones Genetics Epigenetics Endocrine disruptors Immune response Self-organization Social factors? Differences in the Hypothalamus in Relation to Sex and Gender Dysphoria Hypothalamic differences in relation to gender identity Hypothalamic differences in relation to sexual orientation Conclusions Acknowledgements References Chapter 32: Klinefelter syndrome or testicular dysgenesis: Genetics, endocrinology, and neuropsychology Definition Prevalence Testicular Dysgenesis and Hypothalamic-Pituitary-Gonadal Axis Function Infertility Cancer Metabolic Disorders Body composition Metabolic syndrome Type 2 diabetes Lipid profile, atherosclerosis, blood pressure and cerebrovascular diseases Neurologic Disorders in Klinefelter Syndrome Epilepsy and seizures Tremor Neurocognitive Phenotype General cognitive abilities Language deficits Executive dysfunction Hypogonadism and testosterone therapy Personality, Social Dysfunction, Psychiatric Disorders, and Sexual Orientation Personality Social dysfunction Psychiatric disorders Sleep Sexual orientation Brain Structure and Function Structural brain correlates Functional brain correlates Genetics and Epigenetics Paternal origin of the supernumerary X-chromosome Skewed X-chromosome inactivation Androgen receptor polymorphism X-chromosomal gene dosage effect Genome-wide alterations Copy number variants and single nucleotide polymorphisms Clinical management Conclusion References Chapter 33: Neurobiology of puberty and its disorders Introduction Overview of Operation of Mature Hypothalamic-Pituitary-Gonadal Axis Chronology of Pubertal Development and Stages Pubertal staging Secular trends and racial and ethnic differences in the onset and tempo of puberty Ontogeny of Hypothalamic GnRH Pulse Generation (Fetal to Pubertal) Neurobiology of Central Restraint Control Systems Governing Timing of Brake Energy Balance and Puberty Disorders of Puberty Disorders Associated With Early Puberty Incomplete or nonprogressive forms of precocious puberty Approach to the Child with Precocious Pubertal Development Laboratory assessment Imaging studies Treatment of CPP Disorders of Delayed Puberty Hypogonadotropic hypogonadism Constitutional delay in growth and puberty (CDGP) Acquired/functional HH Developmental anomalies of the CNS and pituitary Central nervous system tumors and trauma Pituitary-Dependent Hypogonadotropism (Pituitary Hypogonadism) Primary gonadal failure RASopothies Approach to the Child With Delayed Pubertal Development Estrogen replacement Androgen replacement Psychosocial considerations for precocious and delayed puberty Conclusion References Index Back Cover