دانلود کتاب DeGroot's Endocrinology-Basic Science and Clinical Practice

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Front Matter
DeGroot’s ENDOCRINOLOGY: Basic Science and Clinical Practice
Copyright
sTOC
Vol I
Chapter (1)
1 - Principles of Endocrinology
Definition and Scope of Endocrinology
Historical Perspectives
Principles of Hormone Action
Hormone Biosynthesis and Secretion
Feedback Regulation
Paracrine and Autocrine Regulation
Hormonal Rhythms and Pulsatility
Hormone Transport and Degradation
Hormone Action Through Receptors
Membrane Receptors
Nuclear Receptors
Role of the Clinical Endocrinologist
Major Unsolved Problems
References
Chapter (2)
2 - Principles of Endocrine Measurements
Principles of Endocrine Measurements
Introduction and Brief History of Endocrine Assays
Radioimmunoassay
Nonisotopic Immunoassays
Monoclonal Antibodies
Structural Assays
Preanalytic Methods and Harmonization of Assays
Preanalytic Variables
Analytical Parameters
Clinical Parameters
Reference Intervals
General Interferences
Summary
Principle
Modern Example Analytes
Advantages
Disadvantages
Principle
Advantages
Disadvantages
Special Circumstances
Methods for Measurement of Free Hormones
Additional Techniques
Special Circumstances
Plasma Renin Activity Assay and its Modifications
Advantages
Disadvantages
Direct Renin Concentration
Gas Chromatography—Mass Spectrometry
Liquid Chromatography—Tandem Mass Spectrometry
Special Circumstances
Summary and Future Directions
References
Chapter (3)
3 - Endocrine Rhythms, the Sleep-­Wake Cycle, and Biological Clocks
Endocrine Rhythms, the Sleep-­Wake Cycle, and Biological Clocks
Introduction
What Are Biological Rhythms
The Sleep-­Wake Cycle as a Rhythm
Clocks in the Brain and the Periphery
Endocrine Rhythms
Examples of Endocrine Rhythms in Humans
Glucocorticoid Pulsatility
Rhythms in Endocrine Disease
Limitations of Single Timepoint Assessments
Cell Clocks
The Sleep-­Wake Cycle
Sleep Regulation
Sleep Stages
Sleep Mistiming and Human Health
Jet Lag and Social Jet Lag
Summary
Conclusions
References
Chapter (4)
4 - Prolactinomas and Disorders of Prolactin Secretion
History
Epidemiology
Pathogenesis
Pathology
Nontumoral Lesions Associated With Hyperprolactinemia
Pituitary Prolactin-­Secreting Carcinomas
Physiologic Hyperprolactinemia
Pharmacologic Hyperprolactinemia
Pathologic Hyperprolactinemia
Diagnosis of Prolactinomas
Clinical Features
Laboratory Evaluation
Imaging
Treatment
Medical Therapy
Surgical Therapy
Radiotherapy
Therapeutic Advances and Perspectives
Prolactinomas and Pregnancy
Treatment Planning and Follow-­Up
References
Chapter (5)
5 - Hypopituitarism Including Growth Hormone Deficiency
HISTORY
ETIOLOGY OF HYPOPITUITARISM
Hypophysitis
MORBIDITY AND MORTALITY
CLINICAL FEATURES
DIAGNOSIS AND ENDOCRINE EVALUATION
Adrenocorticotropic Hormone Deficiency: Secondary Adrenal Insufficiency
Thyroid-Stimulating Hormone Deficiency: Central Hypothyroidism
Luteinizing Hormone/Follicle-Stimulating Hormone Deficiency: Hypogonadotropic Hypogonadism
Growth Hormone Deficiency
Hypopituitarism Following Pituitary Surgery
HORMONE REPLACEMENT THERAPY
Adrenocorticotropic Hormone Deficiency: Secondary Adrenal Insufficiency
Thyroid-Stimulating Hormone Deficiency Central Hypothyroidism
Luteinizing Hormone/Follicle-Stimulating Hormone Deficiency: Hypogonadotropic Hypogonadism
Growth Hormone Deficiency
Childhood-Onset Growth Hormone Deficiency in Adults
Hormone–Hormone Interactions
PREGNANCY
REFERENCES
Chapter (6)
6 - Acromegaly
Excess Growth Hormone Secretion
Acromegaly
6
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
Epidemiology
Diagnosis
Documenting Growth Hormone Hypersecretion
Localizing the Source of Excess Growth Hormone
Clinical Manifestations
Laboratory Findings
Mortality
Management
Treatment Goals
Surgery
Pituitary Irradiation
Pharmacologic Management (Fig. 6.5)
Integrated Treatment Approach to the Management of Acromegaly
Patients With Likelihood of Good Surgical Outcome
Follow-­Up
Additional Management Considerations
References
Chapter (7)
7 - Cushing Disease
Etiology of Cushing Disease
Cushing Disease
7
Pathophysiology
Clinical Features
Clinical Aspects
Biochemical Diagnosis of Cushing Syndrome
General Considerations
First-­Line Biochemical Investigations
Second-­Line Biochemical Investigations
Other Biochemical Investigations
Establishing Adrenocorticotropic Hormone–Dependency of Cushing Syndrome
Differential Diagnosis of Adrenocorticotropic Hormone–Dependent Cushing Syndrome
Hypercortisolemic States Without Cushing Syndrome
Differentiating Cushing disease From Ectopic Adrenocorticotropic Hormone Syndrome and Ectopic Corticotropin-­Releasing Hormone S...
Treatment of Cushing Disease
General Considerations
Somatostatin Analogs
Dopamine Agonists
Glucocorticoid Receptor–Directed Drugs
Combination of Medical Treatments
Future Medical Treatments
Metabolic Syndrome and Cardiovascular Risk
Muscle
Bone Disease
Mood and Cognitive Function
Autoimmunity
Quality of Life
Mortality in Cushing Disease
Implications for Treatment and Long-­Term Care
Special Conditions
Cushing Disease as an Emergency Condition
Cyclic Cushing Syndrome
Pediatric Cushing Disease
Cushing Disease and Pregnancy
Cushing Disease and Chronic Renal Failure
Future Directions
References
Chapter (8)
8 - Clinically Nonfunctioning Sellar Masses
Clinically Nonfunctioning Sellar Masses
Pituitary Adenomas
Etiology of Pituitary Adenomas
Other Benign Tumors
Malignant Tumors
Pituitary Hyperplasia
Hypophysitis
Other Sellar Masses
Clinical Presentations
Neurologic Presentations
Incidental Finding
Endocrinologic Presentations
Pituitary Apoplexy
Diagnosis
Imaging of the Sellar Region
Endocrinologic Tests
Pathologic Evaluation
Treatment
Surgery
Radiation
Pharmacologic Treatment
Observation
References
Chapter (9)
9 - Thyroid-­Stimulating Hormone–Producing Pituitary Tumors
Epidemiology
Thyroid-­Stimulating Hormone–Producing Pituitary Tumors
9
Etiopathogenesis and Pathology
Etiopathogenesis
Pathology
Clinical Presentation
Differential Diagnosis
Investigation
Step 1 – Clinical Assessment
Step 2 – Exclusion of Laboratory Assay Interference
Step 3 – Distinguishing a Thyroid-­Stimulating Hormone–Secreting Pituitary Adenoma From TRβ Resistance to Thyroid Hormone
Step 4 – Pituitary Imaging
Management
Conclusions
References
Chapter (10)
10 - Pituitary Surgery
Pituitary Adenoma
Pituitary Surgery
10
Rathke’s Cleft Cyst
Craniopharyngioma (see also Chapter 11)
Other Lesions
Preoperative Management
Endocrine Status
Imaging Evaluation
Surgical Technique
Endoscopic Endonasal Approach for Pituitary Adenoma, Rathke’s Cleft Cyst, and Craniopharyngioma
Diabetes Insipidus
Syndrome of Inappropriate Antidiuretic Hormone
Early Remission
Major Complications
Permanent Hypopituitarism
Cerebrospinal Fluid Leak and Meningitis
Cranial Nerve Injury
Postoperative Intrasellar Hematoma
Internal Carotid Artery Injury
Resection And Remission rates
Pituitary Adenoma
Rathke’s Cleft Cyst
Craniopharyngioma (see also Chapter 11)
Pituitary Centers Of Excellence
Conclusion
References
Chapter (11)
11 - Craniopharyngiomas and Parasellar Masses
Craniopharyngiomas and Parasellar Masses
Types of Parasellar Masses
Craniopharyngiomas
Epidemiology
Pathology
Pathogenesis
Imaging Features
Management
Long-­Term Morbidity and Mortality
Rathke’s Cleft Cysts
Epidemiology
Pathology
Pathogenesis
Imaging Features
Management
Meningiomas
Gliomas
Germ Cell Tumors
Langerhans Cell Histiocytosis
Hamartomas
Pituitary Metastasis
References
Chapter (12)
12 - Disorders of Sodium, Diabetes Insipidus and Hyponatremia
Physiology of Sodium and Water Homeostasis
Synthesis and Secretion of Vasopressin
Disorders of Sodium, Diabetes Insipidus and Hyponatremia
12
Cellular Action of Vasopressin
Osmoregulation of Vasopressin Release
Baroregulation of Vasopressin Release
Other Mechanisms Regulating Vasopressin Release
Secretion of Copeptin
Diabetes Insipidus
Hypothalamic Diabetes Insipidus
Nephrogenic Diabetes Insipidus
Primary Polydipsia
Investigation of Diabetes Insipidus
Adipsic Diabetes Insipidus
Treatment of Diabetes Insipidus
Hyponatremia
Morbidity and Mortality
Differential Diagnosis of Hyponatremia
The Syndrome of Inappropriate Antidiuresis
Introduction
Causes of Syndrome of Inappropriate Antidiuresis
Pathophysiology of Syndrome of Inappropriate Antidiuresis
Diagnosis of Syndrome of Inappropriate Antidiuresis
Differential Diagnosis of Syndrome of Inappropriate Antidiuresis
Treatment of Hyponatremia
Factors Affecting Therapy
Treatment of Chronic Hyponatremia Owing to Syndrome of Inappropriate Antidiuresis
Treatment of Acute Hyponatremia
Conclusions
References
Chapter (13)
13. Anatomy and Physiology of the Hypothalamus and Pituitary
Anatomy and Physiology of the Hypothalamus and Pituitary
Anatomy of the Hypothalamus
Blood Supply of the Hypothalamus
The Median Eminence and Tanycytes
Anatomy and Histology of the Pituitary
The Blood Supply of the Pituitary
The Pars Intermedia
The Pars Tuberalis
The Pars Distalis (Anterior Pituitary)
Posterior Pituitary Gland (Neurohypophysis)
Conclusions and Future Directions
References
Chapter (14)
14 - Genetic Disorders of the Pituitary
Genetic Disorders of the Pituitary
Introduction
Familial Isolated Pituitary Adenoma
AIP-­Related Familial Isolated Pituitary Adenoma
X-­Linked Acrogigantism
Syndromic Pituitary Tumors
Multiple Endocrine Neoplasia Type 1
Multiple Endocrine Neoplasia Type 4
Carney Complex
McCune–Albright Syndrome
DICER1 syndrome
Lynch Syndrome
Neurofibromatosis 1 and Tuberous Sclerosis Complex
Somatic Mutations in Pituitary Tumors
Conclusion
References
Chapter (15)
15. Aggressive Pituitary Tumors
Aggressive Pituitary Tumors
Aggressive Pituitary Tumors
Definitions
Pituitary Carcinomas
Aggressive Pituitary Tumors
Epidemiology
Natural History of Pituitary Carcinomas
Predictive Factors of Aggressiveness
Pathological Markers of Aggressiveness
Molecular Markers of Aggressiveness
Treatment
Temozolomide
Therapeutic Perspectives
Conclusion
References
Chapter (16)
16. Radiotherapy in Pituitary Tumors
Radiotherapy in Pituitary Tumors
Introduction
Indications for Pituitary Radiotherapy
Three-Dimensional Conformal Radiotherapy
Stereotactic Radiotherapy Techniques
Radiotherapy Fractionation
Linear Accelerator–Based Stereotactic Radiosurgery
Gamma Knife Stereotactic Radiosurgery
CyberKnife Stereotactic Radiosurgery
Proton Therapy
Development of Radiosurgery
Efficacy of Radiotherapy
Overall Survival
Radiological Tumor Control: Progression-Free Survival
Hormone Normalization
Visual Function
Toxicity of Radiotherapy
Hypopituitarism
Visual Pathway Damage and other Cranial Nerve Injuries
Radionecrosis
Cerebrovascular Disease
Second Brain Tumors
Mortality
Proton Therapy
Summary
Reirradiation
Conclusions and Future Directions
References
Chapter (17)
17. Somatic Growth and Maturation: Growth Hormone and Other Growth Factors
Somatic Growth and Maturation: Growth Hormone and Other Growth Factors
Introduction
Prenatal Considerations
Chronological Age
Growth Status
Growth Rate
Maturity Status
Skeletal Maturity Status
Secondary Sex Characteristics
Maturity Timing
Tempo of Maturation
Evaluation of Children for Disorders of Growth
Growth Charts
Evaluation of Children With Short Stature
History
Physical Examination
Preliminary Laboratory Evaluation
Evaluation for Endocrine Disorders of Growth
Growth Hormone/Insulin Growth Factor-1 Axis
Growth Hormone Release and Action
Diagnostic Approach
Growth Hormone Stimulation Tests
Limitations of Growth Hormone Stimulation Tests
Growth Hormone Treatment (See Also Chapter 18)
Dosing and Monitoring of Growth Hormone Therapy
Evaluation of Children With Tall Stature
Endocrine Causes of Tall Stature
Treatment of Children/Adolescents With Tall Stature
Growth Evaluation of Children With Obesity
Conclusions
References
Chapter (18)
18 - Growth Hormone Deficiency in Children
INTRODUCTION
EPIDEMIOLOGY
PATHOGENESIS
Genetic and Structural Abnormalities
Acquired Defects
The Hypothalamo-Pituitary-Somatotroph Axis
CLINICAL FEATURES
Neonatal Presentation
Infant And Childhood Years
Guidance Derived From Clinical Assessment
Principles of Testing
Diagnosis of Growth Hormone Deficiency
A Practical Approach to Diagnostic Evaluation
TREATMENT
Growth Hormone
Transition to Adult Care
CONCLUSIONS
REFEERENCES
Chapter (19)
19. Basic and Clinical Appetite Regulation and Energy Expenditure
Introduction
Components of Eating Behavior
Appetite Regulation
Leptin, Growth Differentiation Factor 15, and Endocannabinoids
The Role of Genetics and Epigenetics
Components of Energy Expenditure
Resting Metabolic Rate
Thermic Effect of Food
Physical Activity Energy Expenditure
Brown Adipose Tissue and Uncoupled Respiration
Body Weight Regulation
Body Weight Regulation and Eating Behavior: Beyond Homeostasis
Contributions of Components of Total Daily Energy Expenditure With Prospective Weight Change
Physiological Responses to Weight Loss and Weight Regain
The Effects of Exercise on Energy Balance
Conclusions
References
Chapter (20)
20. Obesity: Risk, Risk Factors, and Medical Management
Obesity: Risk, Risk Factors, and Medical Management
20
Diseases Associated With Obesity
Cardiovascular and Cerebrovascular Disease
Type 2 Diabetes Mellitus
Nonalcoholic Fatty Liver Disease
Gastrointestinal Complications
Cancer
Reproductive Health
Obstructive Sleep Apnea
Osteoarthritis
Cognitive Dysfunction and Alzheimer Disease
Therapy for Obesity
Lifestyle Intervention
Pharmacotherapy
Bariatric Surgery
References
Chapter (21)
21. Genetic Syndromes Associated With Obesity
Genetic Syndromes Associated With Obesity
Introduction
Monogenic Obesity Syndromes
Congenital Leptin and Leptin Receptor Deficiency
Proopiomelanocortin and PCSK1 Deficiency
MC4R Deficiency
SIM1 Deficiency
BDNF, TRKB, and sh2b1 Deficiency
Pleiotropic Obesity Syndromes
Prader–Willi Syndrome
Albright’s Hereditary Osteodystrophy
Bardet–Biedl Syndrome
Alstrom Syndrome
Cohen Syndrome
Rare Variants Associated with Obesity
Conclusions
References
Chapter (22)
22. Regulation of Intermediary Metabolism During Fasting, Feeding, and Exercise
Introduction
Regulation of Intermediary Metabolism During Fasting, Feeding, and Exercise
22
Postabsorptive Glucose Utilization
Postabsorptive Fatty Acid Utilization
Fatty Acid Reesterification as a Component of Flux
Postabsorptive Glucose Production
Hormonal Governance of Glucose Production
Glucose Counterregulation
Prandial And Postprandial Intermediary Metabolism
Introduction
Digestion, Absorption, and Enteroendocrine Cells
Insulin and Glucagon Responses
Effects on Energy Expenditure and Respiratory Quotient
Hepatic Glucose Metabolism
Postprandial Adipose Tissue Metabolism
Hepatic Metabolism of Fatty Acids and Lipoproteins
Protein And Amino Acid Metabolism
Exercise Metabolism
Exercise Dramatically Increases Demand For Energy
Energy Metabolism During Exercise
Glucose Metabolism During Exercise
Fatty Acid Metabolism During Exercise
Effects of Exercise Training on Intermediary Metabolism
Summary And Concluding Remarks
References
Chapter (23)
23. Adipose Tissue Function: Metabolic and Endocrine
Different Types of Obesity and Associated Health Risks
Adipose Tissue Function: Metabolic and Endocrine
23
Summary
Adipogenesis And Its Regulation
Adipose Cell Differentiation and Role of Genetic Factors
Role of Aging and Cell Senescence
Summary
Immunometabolism: Its Regulation And Role In Insulin Resistance, Inflammation, And Disease
Linking Inflammation to Insulin Resistance
Summary
Lipid Metabolism In White Adipose Tissue
Lipid Turnover
Methodology
Lipid Uptake and Lipogenesis in Fat Cells
Regulation of Lipolysis
Glucose Metabolism
Summary
Brown versus Beige/Brown Adipose Cells
Aging Reduces Brown and Beige Adipose Cells
Summary
Summary
Adipose Tissue As A Therapeutic Target
Pharmacotherapy in Obesity
Summary
References
Chapter (24)
24. Lipodystrophy Syndromes
Lipodystrophy Syndromes
24
Pathophysiology of Lipodystrophy
Generalized Lipodystrophies
Partial Lipodystrophies
Localized Lipodystrophies
Fat Redistribution and Fat Metabolism
Adipocytokines
Inflammation
Mitochondrial Stress, Oxidative Stress, and the Endoplasmic Reticulum
Other Mechanisms
Lifestyle Modification
Management of Insulin Resistance
Management of Dyslipidemia
Management of Human Immunodeficiency Virus–Infected Patients With Highly Active Antiretroviral Therapy–Induced Metabolic Syndrom...
Management of Cosmetic Appearance
Adipokines in Lipodystrophy
Future Perspectives
Adiponectin
References
Chapter (25)
25. Lipoprotein Metabolism and the Treatment of Lipid Disorders
LIPOPROTEIN METABOLISM
Lipoproteins
Metabolism of Lipids and Lipoproteins
DISORDERS OF LIPID METABOLISM IN PATIENTS WITH DIABETES
Type 1 Diabetes
Type 2 Diabetes
GENETIC BASIS OF LIPID DISORDERS
Monogenic Low-Density Lipoprotein Disorders
Monogenic High-Density Lipoprotein Disorders
Polygenic Lipid Disorders
DIAGNOSIS OF LIPID DISORDERS
MANAGEMENT/TREATMENT
Dietary and Drug Treatment of Lipid Disorders
REFERENCES
Chapter (26)
26. Metabolic Syndrome
DIAGNOSIS AND PREVALENCE
HISTORY
Obesity, Type 2 Diabetes, Insulin Resistance, and Cardiovascular Disease
The Lipid Theory
Inflammation and Oxidative and Endoplasmic Reticulum Stress
Specific Tissues
AMPK and SIRT1
AMPK and Metabolic Syndrome in Humans
DIAGNOSIS
CORONARY HEART DISEASE AND TYPE 2 DIABETES
Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis
Polycystic Ovarian Syndrome
Certain Cancers
Alzheimer Disease
Cushing Syndrome and Related Disorders
Lipodystrophy
Hyperalimentation
TREATMENT OF METABOLIC SYNDROME
Lifestyle Modification (Weight Loss and Physical Activity)
Drug Therapy
Special Considerations
CHILDREN AND ADOLESCENTS
ACKNOWLEDGMENTS
REFERENCES
Chapter (27)
27. Bariatric Procedures and Operations
Bariatric Procedures and Operations
Introduction/Overview
Commonly Performed Bariatric Operations
The Physiology Of Weight Loss After Bariatric Operations And Procedures
Physiologic Effects Of Bariatric Surgery On Cardiometabolic Health And Mortality
Late and Chronic Complications
Weight Regain
Dumping Syndrome
Summary
Chapter (28)
28. Development of the Endocrine Pancreas
Pancreas Morphogenesis
Early Organ Specification And Bud Formation
Tissue Interaction and Signaling Pathways
Induction of the Pancreatic Gene Expression Program
Cell Type Differentiation
Signaling Pathways
Transcription Factors
Islet Formation
References
Chapter (29)
29. Regulation of Islet Hormone Synthesis and Secretion
Hormonal Synthesis
Insulin
Regulation of Islet Hormone Synthesis and Secretion
29
Glucagon
Hormonal Secretion and Action
Insulin
Glucagon
Glucagon-Like Peptide-1 Secretion and Signaling
References
Chapter (30)
30. Mechanisms of Insulin Action
30
Introduction
Insulin
Introduction
Regulation of the Insulin Receptor Tyrosine Kinase
The Insulin Receptor–Related Receptor
The Insulin Signaling Cascade
Introduction
Insulin Receptor Tyrosine Protein Scaffolds
The IRS→PI3K→AKT Cascade
Insulin-Regulated Proteostasis
Insulin-Regulated Glucose Transport
Heterologous Regulation of Insulin Signaling Cascades
Proximal Insulin Signals
Transcriptional Control of Insulin Receptor Substrate 1
Transcriptional Control of Insulin Receptor Substrate 2
Regulation of Insulin Receptor Substrate Degradation
Regulation by Protein and Lipid Phosphatases
miRNA-Mediated Posttranscriptional Regulation
Mouse Genetics Reveal Tissue-Integrated Insulin Signaling
Introduction
Systemic Insulin Receptor Signaling Cascade
Hepatic InsR─┤FoxO1 Signaling
Adipose Insulin Signaling
Insulin/IGF Signaling in Neurodegenerative Disease
Insulin Resistance and Metabolic Disease
Introduction
Chronic Hyperinsulinemia
Nutrient Excess
Proinflammatory Cytokines
References
Chapter (31)
31. Classification and Diagnosis of Diabetes Mellitus
Classification and Diagnosis of Diabetes Mellitus
Definition
Classification
Type 1 Diabetes
Type 2 Diabetes
Other Specific Types of Diabetes
Genetic Defects in β Cell Function
Genetic Defects in Insulin Action
Diseases of the Exocrine Pancreas
Endocrinopathies
Drug- or Chemical-Induced Diabetes
Infections
Uncommon Forms of Immune-Mediated Diabetes
Other Genetic Syndromes Sometimes Associated With Diabetes
Gestational Diabetes
Diagnosis
Diagnostic Criteria
What Level of Fasting Plasma Glucose Constitutes Diabetes
What’s New
References
Chapter (32)
32. Autoimmune (Type 1) Diabetes Mellitus: Etiology, Pathogenesis, Prediction, and Prevention
Epidemiology
Prevalence
Autoimmune (Type 1) Diabetes Mellitus: Etiology, Pathogenesis, Prediction, and Prevention
32
Incidence
Geographical Distribution
Variation with Age
Variation With Gender
Seasonal Variation
Inheritance
Natural History and Disease Staging
Etiology
Genetic Etiology
Environmental Etiology
Pathogenesis
Humoral Immunopathophysiology
Cellular Immunopathophysiology
Diagnostic Criteria
Prediction
Prevention
Primary Prevention
Secondary Prevention
Intervention
Summary and Future Directions
References
Chapter (33)
33. Type 2 Diabetes Mellitus: Etiology, Pathogenesis, and Natural History
Epidemiology
Type 2 Diabetes Mellitus: Etiology, Pathogenesis, and Natural History
33
Origins of the Disease: Etiologic Factors
Region, Race, Ethnicity, and Genetic Factors
Environment and the Social Determinants of Health
Behavior and Culture
Biological Factors
Natural History of Diabetes as an Evolving Glucoregulatory Defect
Diagnosis of Type 2 Diabetes
Overview of the Evolving Glucoregulatory Defect
Progression of Abnormal Glucose Tolerance
Mechanisms Causing Pancreatic β Cell Dysfunction
The Pathophysiology of Insulin Resistance
Measurement of Insulin Sensitivity in Humans: Defect in Muscle Glucose Uptake
Hepatic Insulin Resistance
The Molecular Basis of Human Insulin Resistance in Target Tissues
General Principles
Insulin Resistance at the Level of the Insulin Receptor
Insulin Resistance at the Level of Signal Transduction
Cell Stress Responses and Insulin Action
Nutrient Sensors and Nutrient Stress
Syndromes of Severe Insulin Resistance
Heterogeneity of Type 2 Diabetes
Severe Insulin Resistance
The Spectrum of Cardiometabolic Disease
Role of Obesity
References
Chapter (34)
34. Diabetes Mellitus and Pregnancy
Metabolic Effects of Pregnancy
Diabetes Mellitus and Pregnancy
34
Classification of Diabetes in Pregnancy
Diagnostic Criteria for Gestational Diabetes Mellitus
Glucokinase Monogenic Diabetes and Pregnancy
Bariatric Surgery and Gestational Diabetes
Diabetes and Pregnancy and the Offspring
Congenital Malformations and Early Fetal Loss
Disturbances of Metabolism and Fetal Growth
Maternal Obesity and the Offspring
Management of Diabetes in Pregnancy
Contraception and Preconception Management
Management of Type 1 Diabetes Mellitus in Pregnancy
Glycemia Monitoring
Diet and Physical Activity
Insulin Management
Management of Diabetes Complications in Pregnancy
Management of Gestational Diabetes Mellitus
Prevention of Gestational Diabetes
Obstetric Management of Diabetes in Pregnancy
Obstetric Surveillance
Antenatal Steroids for Preterm delivery
Hypertensive Disorders of Pregnancy
Decrease in Insulin Requirements
Peripartum Management and Birth
Long-Term Outcomes and Management of Gestational Diabetes
Long-Term Risks of Gestational Diabetes to the Mother
Benefits of Breastfeeding for the Mother
Postpartum Follow-up of Mothers
Postpartum Follow-Up of Offspring
Risk of Obesity to the Offspring
Potential Mechanisms for Long-term Effects of Preexisting Maternal Diabetes and Gestational Diabetes on the Offspring
Summary and Future Directions
References
Chapter (35)
35. Hyperglycemia Secondary to Non-Traditional Diabetic Conditions
Hyperglycemia Secondary to Non-Traditional Diabetic Conditions
Pancreatectomy
Acute Pancreatitis
Chronic Pancreatitis
Pancreatic Cancer
Autoimmune Pancreatitis
Hemochromatosis
Hemosiderosis
Cystic Fibrosis
Acromegaly
Growth Hormone Treatment
Cushing Syndrome
Glucagonoma Syndrome
Somatostatinoma
Pheochromocytoma
Hyperglycemia in Critical Care Patients
Drugs That can Cause Hyperglycemia
Drugs That Directly Adversely Affect β Cell Function
Drugs That Inhibit Increases in β Cell Cytosolic Calcium
Drugs That Cause Potassium Depletion
Antiimmune and Cancer-Treatment Drugs
Drugs That Cause Insulin Resistance
Oral Contraceptives and Sex Hormones
Nicotinic Acid
Lipid-Lowering Agents and New-Onset Diabetes Mellitus
Statins
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors
Cholesterol Ester Transfer Protein Inhibitors
Acquired Immunodeficiency Syndrome and Antiretroviral Drugs
Atypical Antipsychotic Agents
Conclusion
References
Chapter (36)
36. β Cell Glucose Toxicity and Oxidative Stress
36
Introduction
Brief Overview of the Contributions of Oxidative Stress to Secondary Complications of Diabetes
References
Chapter (37)
37. Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State
Epidemiology
Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State
37
Pathogenesis of Diabetic Ketoacidosis
Precipitating Factors
Diagnosis of Diabetic Ketoacidosis
Treatment
Complications of Therapy
Prevention
Hyperglycemic Hyperosmolar State
Epidemiology
Pathophysiology
Precipitating Events
Diagnosis
Treatment
Complications
Prevention
References
Chapter (38)
38. Hypoglycemia and Hypoglycemic Syndromes
Accurate Measurement of Blood or Plasma Glucose
Physiology of Hypoglycemia
Brain Fuel Metabolism
Hypoglycemia and Hypoglycemic Syndromes
38
General Approach to the Patient
Acute Treatment of Hypoglycemia
Evaluation of the Hypoglycemic Patient
Hypoglycemia in Diabetes
Mortality and Cardiovascular Disease
Strategies to Reduce Hypoglycemia
Hypoglycemia in the Absence Of Diabetes
Hypoglycemia in Medicated or Ill Individuals
Hypoglycemia in Apparently Well Individuals
Endogenous Hyperinsulinism
Neonatal Hypoglycemia
Conclusion and Future Directions
References
Chapter (39)
39. Treatment of Type 1 Diabetes Mellitus in Adults
39
Goals Of Management
Glycemic Goals
Acute Complications
Chronic Complications
Quality Of Life
Team Approach To Management
Monitoring
Glycemic Control
Ketone Testing
Complication Surveillance
Insulin Therapy
Principles of Insulin Replacement
Insulin Preparations
Intensive Insulin Therapy Regimens
Adjustment of Insulin Therapy in Special Situations
Nutrition
Other Therapies For Type 1 Diabetes
Metformin, DPP-IV Inhibitors, and GLP-1 RAs
Future Perspectives
References
Chapter (40)
40. Clinical Management of Type 2 Diabetes Mellitus
Diabetes Education
Clinical Management of Type 2 Diabetes Mellitus
40
Individualization of the Diabetes Education Care Plan
Nutrition
Nutrition Therapy––the Evidence
Individualization of the Nutrition Prescription
Summary
Physical Activity
Pharmacotherapy Of Type 2 Diabetes
Metformin
Thiazolidinediones
Insulin Secretagogues
Incretin-Based Therapies
Glucagon-Like Peptide-1 Receptor Agonists
Dipeptidyl Peptidase Inhibitors
α-Glucosidase Inhibitors
Insulin Therapy In Type 2 Diabetes
Short-Acting Insulin Analogs
Long-Acting Insulin Analogs (Table 40.5)
Initial Therapy (Fig. 40.1)
Initial Combination Therapy
Diabetes Technology
Self-Monitoring of Blood Glucose
Digital Health Technology
Telemedicine
Population Management
Conclusion
References
Chapter (41)
41. Pancreas and Islet Transplantation
Pancreas and Islet Transplantation
Introduction
Historical Perspective
Pancreas Transplantation
Patient Selection for Pancreas Transplantation
Surgical Approaches to Pancreas Transplantation
Patient and Graft Survival After Pancreas Transplant
Metabolic Outcomes
Allogeneic Islet (Alloislet) Transplantation
Patient Selection for Alloislet Transplantation
Surgical Approaches to Alloislet Transplantation
Patient and Graft Survival After Alloislet Transplant
Metabolic Outcomes
Immunosuppressive Drugs
Autologous Islet (Autoislet) Transplantation
Patient Selection for Autoislet Transplantation
Surgical Approaches to Autoislet Transplantation
Patient and Graft Survival After Autoislet Transplant
Metabolic Outcomes
Effect of Successful Pancreas or Islet Transplantation on Complications of Diabetes
Future Directions and Conclusions
References
Chapter (42)
42. Diabetes and Long-Term Complications
Diabetes and Long-Term Complications
History
Classification
Rheumatic, Dermatologic, and Infectious Manifestations
Epidemiology
Pathophysiology
Can We Prevent Macrovascular Disease
Effects of Specific Hypoglycemic Agents on Cardiovascular Disease and Renal Outcomes in Patients With Type 2 Diabetes
Conclusion
References
Chapter (43)
43. Diabetic Eye Disease
Diabetic Eye Disease
43
Natural History of Diabetic Retinopathy
Proliferative Diabetic Retinopathy
Diabetic Macular Edema, Ischemia, and Traction
Nonproliferative Diabetic Retinopathy Levels
Proliferative Diabetic Retinopathy Levels
Epidemiology
Prevalence and Incidence of Retinopathy
Risk Factors for Diabetic Retinopathy
Diabetes-Related Risk Factors
Other Risk Factors
Other Ocular Diseases Associated With Diabetes
Glaucoma
Visual Impairment
Detection
Telemedicine Programs for Diabetic Retinopathy
Management
Ophthalmic
Surgical
Rehabilitation
Protective and Risk Factors for Diabetic Retinopathy
Novel Therapies
References
Chapter (44)
44. Diabetic Neuropathy
Diabetic Neuropathy
Definition of Diabetic Neuropathies
Classification of Diabetic Neuropathies
Pathogenesis
Distal Symmetrical Polyneuropathy
Epidemiology
Screening and Diagnosis in Clinical Care
Secondary Distal Symmetric Polyneuropathy Complications: Diabetic Foot Ulcers/Charcot Neuroarthropathy
Distal Symmetric Polyneuropathy Treatment
Diabetic Autonomic Neuropathies
Cardiovascular Autonomic Neuropathy
Cardiovascular Autonomic Neuropathy Evaluation in Clinical Research
Treatment
Gastrointestinal Autonomic Neuropathy
Urogenital Autonomic Neuropathy
Sudomotor Dysfunction
Atypical Neuropathies
Mononeuropathies
Diabetic Radiculoplexus Neuropathy
Conclusions
References
Chapter (45)
45. Diabetic Kidney Disease
Diabetic Kidney Disease
Epidemiology
Risk Factors
Diagnosis and Classification
Biomarkers
Natural History
Structural Changes of the Kidney
Pathophysiology
Increased Glucose Uptake in the Diabetic Kidney
Hemodynamic Abnormalities
Mechanotransduction
Inflammation and Fibrosis
Epigenetic Changes
Treatment
Glycemic Control
Glucose-Lowering Agents
Blood Pressure Control
Cardiovascular Risk Reduction
Nutrition Management
Additional Interventions and Management Approaches
Summary and Future Directions
References
Chapter (46)
46. Diabetic Foot and Vascular Complications
Pathophysiology
Diabetic Foot and Vascular Complications
46
Neuropathy
Infection
Ischemia
Bone and Joint Abnormalities
Presentation and Diagnosis
Diabetic Foot Ulcers
Infection/Osteomyelitis
Peripheral Arterial Disease
Medical Management
Prevention and Screening
Antibiotics
Wound Care
Offloading
Surgical Management
Drainage Procedures
Lower Extremity Arterial Reconstruction
Endovascular Procedures
Amputations
Multidisciplinary Approach
Future Trends
References
Chapter (47)
47. Parathyroid Hormone and the Parathyroid Hormone Receptor Type 1 in the Regulation of Calcium and Phosphate Homeostasis and Bone Metabolism
Parathyroid Hormone
Parathyroid Hormone Chemistry
Evolution of Parathyroid Hormone Ligands
The Parathyroid Hormone Gene and its mRNA
Regulation of Parathyroid Hormone Gene Expression
Regulation of Parathyroid Hormone Secretion
Mechanism of Extracellular Calcium Ion Sensing by Parathyroid Cells and Other Cells Involved in Mineral Ion Homeostasis
Metabolism of Parathyroid Hormone
Actions of Parathyroid Hormone on the Kidney
Renal Calcium Reabsorption
Regulation of 1α- and 24-Hydroxylase Activity
Renal Phosphate Transport
Actions of Parathyroid Hormone on Bone
Molecular Properties Of The Parathyroid Hormone Receptor Type-1
Gene Structure, Protein Topology, and Evolution
Disease Mutations in the PTHR-1 and its Ligands
Summary
References
Chapter (48)
48. Parathyroid Hormone-Related Protein
Parathyroid Hormone-Related Protein
The Skeleton
The Mammary Gland
The Skin
Placenta
Endocrine Pancreas
Smooth Muscle and the Cardiovascular System
Teeth
The Nervous System
The Immune System
Cancer
Skeletal Disease
Skin Disease
Diabetes
Conclusion
References
Chapter (49)
49. Calcitonin
49
Calcitonin Chemistry
Calcitonin Gene
Calcitonin Gene Alternative Product
Calcitonin Receptors
Receptor Gene
Receptor Isoforms
Receptor Polymorphisms
Receptor Distribution
Calcitonin–Calcitonin Receptor Signaling
Receptor Regulation
Calcitonin Physiology
Calcitonin in Growth and Development
Calcitonin in Calcium Stress: Pregnancy and Lactation
Renal Actions of Calcitonin
Calcitonin in the Central Nervous System
Peptides Related to Calcitonin
Calcitonin and its Receptors in Cancer
Medullary Carcinoma of the Thyroid
Calcitonin Receptors in Other Cancers
Calcitonin As a Therapeutic
Hypercalcemia
Osteoporosis and Paget Disease of Bone
Osteoarthritis
Conclusion
References
Chapter (50)
50. Vitamin D: From Photosynthesis, Metabolism, and Action to Clinical Applications
Vitamin D: From Photosynthesis, Metabolism, and Action to Clinical Applications
Historic Overview
Metabolism of Vitamin D
25-Hydroxylation
1α-Hydroxylation
24-Hydroxylation: Catabolism or Specific Function
Vitamin D Transport
Action and Mode of Action
General Characteristics of the Vitamin D Receptor
Classic Target Tissues
Clinical Consequences of Vitamin D Status
Skeletal Effects of the Vitamin D Endocrine System
Extraskeletal Actions of the Vitamin D Endocrine System
Clinical Use of Vitamin D
Optimal Serum 25OHD Concentration
Worldwide Vitamin D Status
Vitamin D Requirements
Summary
References
Chapter (51)
51. Bone Development and Remodeling
Intramembranous Ossification
Bone Development and Remodeling
51
Endochondral Ossification
Principles of Bone Remodeling and Skeletal Homeostasis
The Bone Remodeling Cycle
Cellular and Molecular Control of Skeletal Development and Bone Remodeling
Chondrogenesis and Growth Plate Biology
Skeletal Vascularization
Skeletal Stem and Progenitor Cells
Osteoblastogenesis
Osteoclastogenesis and Skeletal Tissue Resorption
Regulation of Bone Remodeling and Bone Mass
Coupling of Bone Resorption and Bone Formation During Remodeling
Conclusion
References
Chapter (52)
52. Regulation of Calcium Homeostasis and Genetic Disorders That Affect Calcium Metabolism
Distribution and Metabolic Actions of Calcium
Regulation of Calcium Homeostasis and Genetic Disorders That Affect Calcium Metabolism
52
Calcium Absorption
Mechanisms and Sites of Calcium Absorption
Renal Calcium Excretion
Sites and Mechanisms of Renal Calcium Reabsorption
Regulation of Renal Calcium Reabsorption
PTH Gene Structure and Function
Hypercalcemic Diseases
Parathyroid Tumors
Syndromic Forms of Primary Hyperparathyroidism
Nonsyndromic Forms of Primary Hyperparathyroidism
Other Hereditary Hypercalcemic Disorders
Hypocalcemic Disorders
Hypoparathyroidism
PTH Gene Abnormalities
GCM2 Abnormalities
X-Linked Recessive Hypoparathyroidism
Pluriglandular Autoimmune Hypoparathyroidism
DiGeorge Syndrome
Charge Syndrome
Calcium-Sensing Receptor Abnormalities
Blomstrand Disease
Conclusion
References
Chapter (53)
53. Genetic Disorders of Phosphate Homeostasis
Regulation of Phosphate Absorption
Phosphate Excretion
Genetic Disorders of Phosphate Homeostasis
53
Regulation of Phosphate Reabsorption
Fibroblast Growth Factor-23
Fibroblast Growth Factor-23 Activity
Regulation of Fibroblast Growth Factor-23 Production
Disorders Associated with Increased FGF23 Bioactivity
Disorders Associated With Reduced Fibroblast Growth Factor-23 Bioactivity
Possible Future Therapeutic Avenues
References
Chapter (54)
54. Primary Hyperparathyroidism
Primary Hyperparathyroidism
Introduction
Epidemiology, Diagnosis, and Overview of Clinical Features
Incidence
Diagnosis and Differential Diagnosis
Other Biochemical Features
Clinical Presentation
The Skeleton
Bone Turnover Markers
Bone Densitometry
Bone Histomorphometry
New Imaging Technologies
Fractures
Nephrolithiasis and Renal Function
Other Organ Involvement
Cardiovascular System
Neurological, Psychologic and Cognitive Features
Gastrointestinal Manifestations
Other Systemic Involvement
Unusual Presentations
Neonatal Primary Hyperparathyroidism
Primary Hyperparathyroidism in Pregnancy
Acute Primary Hyperparathyroidism
Parathyroid Cancer
Evaluation
Natural History
Natural History With Surgery
Natural History Without Surgery
Guidelines for Parathyroidectomy
Surgery
Surgical Approach
Immediate Postoperative Course
Medical Management
General Measures
Diet and Supplements
Pharmaceuticals
Hydrochlorothiazide
Treatment of Parathyroid Cancer
Summary
References
Chapter (55)
55. Malignancy-Associated Hypercalcemia
Malignancy-Associated Hypercalcemia
Introduction and History
Normal Physiology of Calcium Metabolism
Parathyroid Hormone and the Calcium-Sensing Receptor
Vitamin D
Parathyroid Hormone–Related Protein
Malignancy-Associated Hypercalcemia
Humoral Hypercalcemia of Malignancy
Local Osteolytic Hypercalcemia
Overproduction of 1,25-Dihydroxyvitamin D
Ectopic Production of Parathyroid Hormone
Treatment
Hydration
Inhibition of Bone Resorption
Glucocorticoids
Dialysis
Other treatments
References
Chapter (56)
56. Surgical Management of Hyperparathyroidism
Clinical Presentation
Indications for Surgery
Surgical Management of Hyperparathyroidism
56
Preoperative Preparation
Operative Approaches
Intraoperative Adjuncts
Postoperative Management
Outcomes of Parathyroid Surgery
Reoperative Parathyroid Surgery
Hypercalcemic Crisis
Inherited Syndromes
Parathyroid Carcinoma
Pediatric Parathyroid Surgery
Hyperparathyroidism in Pregnancy
Secondary Hyperparathyroidism
Tertiary Hyperparathyroidism
COVID-19 and Parathyroid Surgery
Summary
References
Chapter (57)
57. Pseudohypoparathyroidism, Albright’s Hereditary Osteodystrophy, and Progressive Osseous Heteroplasia: Disorders Caused by GNAS Mutations that Reduce Gsα Activity
Pseudohypoparathyroidism, Albright’s Hereditary Osteodystrophy, and Progressive Osseous Heteroplasia: Disorders Caused by GNAS M...
Pseudohypoparathyroidism Type-Ia
The Complex Gnas Locus
The Alpha Subunit of the Stimulatory G Protein (Gsα)
Pseudopseudohypoparathyroidism
Progressive Osseous Heteroplasia
Disorders of Concurrent Gsα Inactivity and Hyperactivity
Pseudohypoparathyroidism Type-Ib
Autosomal Dominant PHP1B
Sporadic Pseudohypoparathyroidism Type-1B
Pseudohypoparathyroidism Type-II
Acrodysostosis With Hormonal Resistance
Treatment
Summary
References
Chapter (58)
58. Genetic Defects in Vitamin D Metabolism and Action
Genetic Defects in Vitamin D Metabolism and Action
Overview of Vitamin D Metabolism
Rickets and Osteomalacia
Vitamin D–Deficiency Rickets, Vitamin D Hydroxylation–Deficient Rickets, and Vitamin D–Dependent Rickets
CYP2R1 Mutations
CYP27B1 Mutations
Vitamin D Receptor Mutations
Treatment OF Vitamin D-Dependent Rickets, Type 2A
Idiopathic Infantile Hypercalcemia
CYP24A1 Mutations
Future Directions
References
Chapter (59)
59. Hereditary Disorders of the Skeleton
Hereditary Disorders of the Skeleton
Dense Bone Disorders
Osteopetroses
Pycnodysostosis
Kenny–Caffey Syndrome
Infantile Cortical Hyperostosis (Caffey Disease)
Endosteal Hyperostoses
Osteopoikilosis
Osteopathia Striata
Pachydermoperiostosis
Paget Disease of Bone
Familial Expansile Osteolysis
Osteoprotegerin Deficiency
References
Chapter (60)
60. Osteoporosis
Osteoporosis
What Is Osteoporosis
Origins of Skeletal Fragility
Bone Density
Bone Quality
Falls and Frailty
Nutrition
Genetics
Epidemiology
Bone Mineral Density
Fractures
Assessing Patients at Risk of Fracture
Fracture Risk Assessment
Bone Turnover Markers
Skeletal Imaging
Other Investigations
Lifestyle
Antiresorptive Medications
Anabolic Medications
Treatment Decisions
Whom to Treat
Selection of Treatment
How Long to Treat
Follow-Up
Management of Subtypes of Osteoporosis
References
Chapter (61)
61. CKD-MBD Syndrome: Chronic Kidney Disease Produced Disorders in Skeletal, Vascular, and Cardiac Tissues and Mineral Metabolism
Vascular
CKD-MBD Syndrome: Chronic Kidney Disease Produced Disorders in Skeletal, Vascular, and Cardiac Tissues and Mineral Metabolism
61
Cardiac
Skeletal
Plasma
Pathogenesis
Pathogenic Factors in the Chronic Kidney Disease–Mineral and Bone Disorder
FGF23
Klotho
Sclerostin
Hyperphosphatemia
Calcitriol Deficiency
Hypocalcemia
Hyperparathyroidism
Hypogonadism
Other Factors
Pathology of Renal Osteodystrophy
Low-Turnover Bone Disease, Adynamic Bone Disorder
Associated Features
Osteoporosis and Osteosclerosis
Management of Osteoporosis in Chronic Kidney Disease
Clinical Manifestations
Bone Pain, Fractures, and Skeletal Deformities
Conclusion
References
Chapter (62)
62. Disorders of Mineralization
Disorders of Mineralization
62
Radiologic Features
Nutritional Osteomalacia and Rickets
Gastrointestinal Diseases
Disorders of Vitamin D Metabolism
Hypophosphatemia
FGF23-Mediated Hypophosphatemia
Non–FGF23-mediated Hypophosphatemia
Miscellaneous Causes of Impaired Mineralization
Acidosis
Fanconi Syndrome
Chronic Kidney Disease
Aluminum, Fluoride, and Heavy Metal Intoxication
Hypophosphatasia
Osteopetrosis
Fibrogenesis Imperfecta Ossium
Treatment
Conclusion
References
Chapter (63)
63. Paget Disease of Bone
Paget Disease of Bone
63
Pathophysiology
Clinical Features
Regional Manifestations
Biochemical Features
Indices of Bone Resorption
Indices of Bone Formation
Calciotropic Hormones
Systemic Complications and Associated Diseases
Primary Hyperparathyroidism, Nephrolithiasis, Hypercalciuria, Hypercalcemia
Hyperuricemia and Gout
Cardiovascular Abnormalities
Drug Treatment
Indications for Treatment
Pretreatment Laboratory Evaluation
Calcitonin
Bisphosphonates
Surgery
Causes
Animal Models of Paget Disease
References
Vol II
Chapter (64)
64. Anatomy and Development of the Thyroid
The Anatomy Of The Thyroid Gland
Gross Anatomy
Blood Supply
Lymphatics
Innervation
Anatomic Variants
Other Thyroid Cells
C Cells
Ultimobranchial Body-Derived Epithelial Cells
Thyroid Stem Cells
The Development Of The Thyroid Gland
Differentiation of C Cells
Functional Genomics of Thyroid-Enriched Transcription Factors
From Animal Models to Human Diseases
Generation of Functional Thyroid Follicles In Vitro
Phylogenesis Of The Thyroid Gland
References
Chapter (65)
65. Thyroid-Stimulating Hormone and TSH Receptor
Thyroid-Stimulating Hormone and TSH Receptor
65
Regulation of Thyroid-Stimulating Hormone Secretion
Hypothalamic Regulation of Thyroid-Stimulating Hormone Secretion
Thyrostimulin
Thyroid-Stimulating Hormone Receptor
Protein Structure
Thyroidal Actions of Thyroid-Stimulating Hormone
Regulation of Thyroid-Specific Gene Expression
Thyroid-Stimulating Hormone Receptor/Insulin-Like Growth Factor 1 Receptor Crosstalk
Regulation of Thyroid Hormone Synthesis
Regulation of Thyroid Hormone Secretion
References
Chapter (66)
66. Thyroid Hormone Transporters and Metabolism
Thyroid Hormone Transporters and Metabolism
Disorders Of Thyroid Hormone Transport
MCT8 Deficiency
Disorders Of Thyroid Hormone Metabolism
Iodothyronine Deiodinase I Deficiency
SBP2 Deficiency
Sec-tRNA[Ser]Sec
References
Chapter (67)
67. Thyroid Hormone Action
Thyroid Hormone Action
Components Of Thyroid Hormone Action
Thyroid Hormone Receptor Coregulatory Proteins
Thyroid Hormone Receptor Posttranslational Modifications
Nongenomic Thyroid Hormone Action
Thyroid Hormone Tissue-Specific Actions
Thyroid Hormone Receptor Isoform–Specific Expression
Growth
Stem Cell Proliferation
Thyroid Hormone and Somatic Growth
Brain
Heart and Blood Vessels
Skeletal Muscle
Skeletal System
Small Intestine
Metabolic Regulation and Actions in Liver
White and Brown Adipose Tissue
Skin
Resistance to Thyroid Hormone Beta
Resistance to Thyroid Hormone Alpha
References
Chapter (68)
68. Thyroid Function Testing (Thyrotropin, Triiodothyronine, and Thyroxine)
Thyroid Function Testing (Thyrotropin, Triiodothyronine, and Thyroxine)
Introduction
THYROTROPIN
Immunoassay for Thyrotropin
Thyrotropin Reference Intervals
Standardization of Thyrotropin Immunoassays
Free Thyroid Hormones
Indirect Estimation of Free Thyroid Hormones
Free Thyroid Hormones by Equilibrium Dialysis
Immunoassay of Free Thyroid Hormones
Free Thyroid Hormone Reference Intervals
Standardization of Free Thyroid Hormones
Total Thyroxine And Triiodothyronine
Future Directions
References
Chapter (69)
69. Thyroid Imaging
Indications for Sonographic Assessment
Physics of Ultrasonography
Thyroid Imaging
69
Diffuse Thyroid Disorders
Primary Thyroid Lymphoma
Subacute Thyroiditis
Sonographic Risk Stratification Systems
Korean Thyroid Imaging Reporting and Data System
Specialized Sonographic Techniques
Scintigraphy
Thyroid Nodules
Diffuse Thyroid Disorders
Congenital Hypothyroidism
Perchlorate Discharge Test
Incidentalomas
Future Directions
References
Chapter (70)
70. Pathology of the Thyroid Gland
Pathology of the Thyroid Gland
Thyroid Gland
Pathologic Assessment Of Thyroid Lesions
Pathology of Thyroid Lesions
Diffuse Enlargements of Thyroid Gland
Nodular Enlargements and Nodules
Benign Neoplasms
Malignant Neoplasms
Papillary Thyroid Carcinoma
Variants of Papillary Cancer
Follicular Carcinoma
Hürthle Cell (Oncocytic Follicular) Tumors
High-Grade Thyroid Carcinoma
Poorly Differentiated Carcinoma
Anaplastic Carcinoma
Familial Follicular-Derived Thyroid Tumors
Medullary Carcinoma
Rare Tumors of Thyroid Gland
Malignant Tumors Arising in Ectopic Thyroid Tissue
Secondary Tumors
Summary and Future Directions
References
Chapter (71)
Chapter (72)
72. Graves’ Orbitopathy
Graves’ Orbitopathy
Epidemiology
Risk Factors
Age
Gender
Ethnicity
Smoking
High Thyroid Stimulating Hormone Receptor Antibody Titer
Radioactive Iodine Therapy
Cholesterol Level and Statin Use
Pathogenesis
Key Pathological Changes in Graves’ Orbitopathy
Thyroid Stimulating Hormone Receptor as the Putative Autoantigen
Immune Dysregulation
Signaling Pathways Mediating Hyaluronan Production and Adipogenesis (Fig. 72.2)
Orbital Infiltration of CD34+ Fibrocytes
Thyroid Stimulating Hormone Receptor and Insulin-Like Growth Factor-1 Receptor Crosstalk (Fig. 72.3)
Genetic Susceptibility
Clinical Manifestations And Diagnosis
Clinical Evaluation
Thyroid Function Test
Thyroid Stimulating Hormone Receptor Antibody
Orbital Imaging
Quality of Life Assessment
Management
General Measures
Mild Graves’ Orbitopathy
Active Moderate-to-Severe Graves’ Orbitopathy
Sight-Threatening Graves’ Orbitopathy
Inactive Graves’ Orbitopathy and the Role of Rehabilitative Surgery
Novel Treatment Approaches for Immunosuppression in Graves’ Orbitopathy
Summary And Perspectives
References
Chapter (73)
73. Thyroiditis
Thyroiditis
Subtypes of Thyroiditis
Hashimoto’s Thyroiditis
Definition and Incidence
Etiopathogenesis and Physiopathologic Mechanisms in Autoimmune Thyroid Disease
Natural History and Clinical Features
Relationship With Other Autoimmune Diseases
Diagnosis
Treatment and Follow-Up
Hashimoto’s Encephalopathy
Acute/Infectious Thyroiditis
Definition and Incidence
Clinical and Diagnostic Features
Treatment and Follow-Up
Subacute Thyroiditis
Definition and Incidence
Pathology
Treatment and Follow-Up
Silent Thyroiditis
Definition and Incidence
Clinical Features
Diagnosis: Clinical, Laboratory, and Imaging Findings
Treatment
Riedel’s Thyroiditis
Definition and Incidence
Etiology
Clinical Features
Diagnosis: Laboratory and Imaging Findings
Pathology
Treatment
IgG4 Thyroiditis
Definition, Incidence, and Relationships in the Setting of Other Subtypes of Thyroiditis
Clinical Aspects
Diagnosis
Treatment and Follow-Up
Summary and Future Directions
References
Chapter (74)
74. Hypothyroidism
Hypothyroidism
Brief History
Hypothalamic-Pituitary-Thyroid Axis
Epidemiology
Clinical Manifestations
Symptoms
Signs
Etiology
Primary Hypothyroidism
Central Hypothyroidism
Peripheral Causes of Hypothyroidism
Diagnosis
Reference Intervals
Serum Thyroid-Stimulating Hormone
Log-Linear Relationship
Free Thyroxine Levels
Triiodothyronine Levels
Thyroid Antibody Testing
Detection of Central Hypothyroidism
Subclinical Versus Overt Hypothyroidism
Screening
Treatment
Levothyroxine Therapy
Therapy Other Than Levothyroxine
Summary and Areas of Future Research
References
Chapter (75)
75. Thyroid and Pregnancy
Epidemiology
Physiology
Thyroid and Pregnancy
75
Physiology During Assisted Reproduction Technology
Clinical Outcomes and Management
Maternal and Fetal Physiology in Pregnancy
Thyroid Function Tests in Pregnancy
Hyperthyroidism in Pregnancy
Diagnosis
Treatment and Monitoring
Lactation
Hypothyroidism and Hypothyroxinemia In Pregnancy
Overt Hypothyroidism
Subclinical Hypothyroidism
Isolated Hypothyroxinemia
Thyroid Autoimmunity in Pregnancy
Associated Obstetric and Fetal Outcomes
Potential Mechanisms for Associations
Implications for Therapy and Monitoring
Screening for Thyroid Dysfunction in Pregnancy
Thyroid Nodules and Cancer During Pregnancy
Thyroid Disorders in the Postpartum Period
Postpartum Thyroiditis
Considerations in Lactating Women
Summary and Future Directions
References
Chapter (76)
76. Iodine Nutrition and the Thyroid
Iodine Nutrition and the Thyroid
Dietary Sources Of Iodine
Absorption and Bioavailability of Iodine
Thyroidal Iodine Uptake
Goitrogens
Metabolism
Thyroidal Adaptation to Iodine Deficiency
Iodine Requirements
Methods To Assess Iodine Status
Urinary Iodine Concentration
Thyroid Size
Thyroid-Stimulating Hormone
Thyroglobulin
Effects of Iodine Deficiency on the Thyroid and Brain
Goiter
Pregnancy and Infancy
Childhood
Adulthood
Epidemiology of Iodine Deficiency
Treatment And Prevention Of Iodine Deficiency
Salt Fortification with Iodine
Iodine Supplementation
Iodine Excess
References
Chapter (77)
77. Euthyroid and Hyperthyroid Nodules and Goiter
Definition and Clinical Manifestation
Environment and Heredity
Euthyroid and Hyperthyroid Nodules and Goiter
77
Hot Thyroid Nodules
Cold Thyroid Nodules
Euthyroid Nodules
Iodine-Induced Hyperthyroidism
Epidemiology, Occurrence, and Natural History of Euthyroid and Hot Thyroid Nodules
Thyroid Nodule Diagnostic Pathway to Distinguish Benign and Malignant Thyroid Nodules
Clinical Examination
Laboratory Investigations
Diagnosis of Thyroid Autonomy
Malignancy Risk Stratification using Thyroid Ultrasound
Fine Needle Aspiration Cytology
Treatment of Autonomous Thyroid Nodules
Surgery
Radioiodine Therapy
Follow-Up
Treatment of Euthyroid Nodules (see Table 77.3)
Iodine Supplementation
Thyroid Hormone Treatment
Surgery
Radioiodine Therapy
Nonsurgical Thermal Ablation of Thyroid Nodules
References
Chapter (78)
78. Differentiated Thyroid Cancer – Streamlining Diagnosis and Optimizing Management
Differentiated Thyroid Cancer – Streamlining Diagnosis and Optimizing Management
Epidemiology
Pathology
Papillary Thyroid Carcinoma Variants
Follicular Thyroid Carcinoma
Hurthle Cell (Oncocytic) Tumors
Poorly Differentiated Thyroid Carcinoma
Causes
Somatic Gene Alterations
Germline Genetic Factors
Ionizing Radiation
Diagnosis, Clinical Features, And Course
Response to Therapy
Prognostic Factors
Age and Gender
Histopathological Factors
Size of the Primary Tumor and Extrathyroidal Extension
Extrathyroidal Extension
Lymph Node Metastases
Therapy And Monitoring
Radioiodine Therapy
Levothyroxine Therapy
Monitoring for Disease Recurrence
Treatment of Metastatic Disease
References
Chapter (79)
79. Medullary Thyroid Cancer
Clinical Presentation And Diagnosis
Sporadic Medullary Thyroid Cancer
Medullary Thyroid Cancer
79
Hereditary Forms (Multiple Endocrine Neoplasia Type II)
Gene Carriers
Pathology And Pathogenesis
Histology
Genetics
Initial Therapy
Postsurgical Follow-Up
Follow-Up of Cured Medullary Thyroid Cancer Patients
Follow-Up of Patients with Biochemical Persistent Disease
Follow-Up of Patients with Structural Disease
Other Therapies
Local Treatment of Recurrent or Persistent Neck Disease
Conclusions
References
Chapter (80)
80. Anaplastic (Undifferentiated) Thyroid Carcinoma
Epidemiology
Clinical Characteristics
Diagnosis
Biopsy
Histopathology Subtypes
Anaplastic (Undifferentiated) Thyroid Carcinoma
80
Differential Diagnoses
Molecular Genetics
Evaluation
Clinical and Labs
Imaging
Staging
Establish Goals of Care
Multidisciplinary Team
Prognosis
Predictors of Survival
Median and Overall Survival
Therapy
Treatment Strategies by Stage
Surgery
Radiation Therapy
Multimodal Therapy
Future Directions
Conclusions
Acknowledgments
References
Chapter (81)
81. Resistance to Thyroid Hormone and Genetic Defects of the Thyroid
Resistance to Thyroid Hormone and Genetic Defects of the Thyroid
Congenital Primary Hypothyroidism
Epidemiology and Screening
Genetic Causes of Thyroid Dysgenesis
Genetic Causes of Dyshormonogenesis
Resistance to Thyroid Hormone β
Clinical Features
Differential Diagnosis
Molecular Genetics
Management
Resistance to Thyroid Hormone Alpha
Background
Clinical Features
Molecular Genetics
Management
References
Chapter (82)
82. Surgical Management of Thyroid Disease
Surgical Management of Thyroid Disease
82
Relevant Surgical Anatomy
The Recurrent Laryngeal Nerve
The External Branch of the Superior Laryngeal Nerve
Parathyroid Glands
Lymphatics
Imaging For Surgical Planning
Ultrasound
Axial Imaging
Molecular Testing And Its Use For Surgical Planning
Indeterminate Nodules
Planning the Extent of Surgery
Diseases Of The Thyroid And Surgical Procedures To Consider
Graves Disease
Hashimoto Thyroiditis
Thyroglossal Duct Cyst and Surgical Excision
Thyroid Hemiagenesis and Agenesis
Ectopic Thyroid and Surgical Excision
Lingual Thyroid
Suprahyoid and Infrahyoid Thyroid
Substernal Goiter
Papillary Thyroid Cancer
Follicular Thyroid Cancer
Hurthle Cell Thyroid Cancer
Medullary Thyroid Cancer
Anaplastic Thyroid Cancer
Radioactive Iodine Therapy
Indications For Surgery Of The Thyroid Gland
Indications for Lobectomy versus Total Thyroidectomy
Indications for Active Surveillance
Indications for Remote Access Surgery
Indications for Prophylactic Central Neck Dissection
Indications for Therapeutic Central Neck Dissection
Indications for Lateral Neck Dissection
Transoral Approach To Thyroidectomy
Open Surgical Techniques
Lobectomy and Total Thyroidectomy
Retrograde Medial Approach to the Thyroid Dissection
Central Neck Dissection
Lateral Neck Dissection
Minimally Invasive Techniques
Radiofrequency Ablation Technique
Surgical Complications
Recurrent Laryngeal Nerve Injury
Hypoparathyroidism
Spinal Accessory Nerve Injury
Greater Auricular Nerve Injury and Sensory Cervical Rootlets
Other Cranial Neuropathies
Chyle Leak
Cosmesis
Complications Associated with Transoral Surgery
Complications Associated with Radiofrequency Ablation
References
Chapter (83)
83. Nonthyroidal Illness Syndrome
Nonthyroidal Illness Syndrome
Low Triiodothyronine States
Serum Hormone Levels
Serum Total and Free Triiodothyronine
Serum Reverse Triiodothyronine
Serum Total and Free Thyroxine
Serum Thyroid-Stimulating Hormone
Thyroid Hormone Transport
Thyroid Hormone Metabolism and Action
Hypothalamus
Pituitary
Liver
Muscle
Adipose Tissue
Neutrophils and Macrophages
Mechanism of Altered Thyroid Hormone Metabolism in Nonthyroidal Illness Syndrome
Cyrokines
Nuclear Factor κB
Alternative Mechanisms
Energy Status
Conclusion
References
Chapter (84)
84. Drugs and Thyroid
Drugs and Thyroid
84
Drugs That Enhance Thyroid Autoimmunity
Drugs Causing Direct Thyroid Damage
Drugs Affecting Protein Binding Of Thyroid Hormone
Changes in Binding Proteins
Displacement of Thyroid Hormone From Binding Proteins
Drugs Affecting Thyroid Hormone Activation, Metabolism, And Excretion
Thyroxine-to-Triiodothyronine Conversion
Thyroid Hormone Metabolism
Disposal of Thyroid Hormone
Summary And Future Directions
References
Chapter (85)
85. Adrenal Development and Homeostasis
Introduction and Historical Background
Anatomy
Adrenal Cortex
Embryonic Adrenal Development
Overview
Adrenal Fate Determination
Fetal Adrenal Development
Postnatal Adrenal Development
Fetal Zone Involution
Establishment of Adrenal Cortex Zonation
Homeostatic Renewal
Role of Renin-Angiotensin-Aldosterone System and Adrenocorticotropic Hormone/PKA Signaling in Regulation of Renewal
Sexual Dimorphism in Renewal
Adrenal Cortex Regeneration
Tissue Stress Progenitors and Adrenal Aging
Conclusion and Future Directions
References
Chapter (86)
86. Genetic Disorders of the Adrenal Cortex
Genetic Disorders of the Adrenal Cortex
Genetic Disorders of the Adrenal Cortex
Steroidogenesis
Hypoplasia
Familial Glucocorticoid Deficiency-Like (FGD-Like)
Other Causes Of Syndromic Adrenal Insufficiency
Conclusion
References
Chapter (87)
87. Enzymes and Pathways of Human Steroidogenesis
87
Cytochrome P450 Enzymes
Hydroxysteroid Dehydrogenases and Reductases
Acute Regulation of Steroidogenesis
Chronic Maintenance of the Steroidogenic Machinery
Human Steroidogenic Cytochrome P450 Enzymes
P450scc (Encoded by CYP11A1)
P450c17 (Encoded by CYP17A1)
P450c21 (Encoded by CYP21A2)
P450aro (Aromatase)
Redox Partner Proteins
Ferredoxin
Ferredoxin Reductase
P450 Oxidoreductase
Cytochrome b5
Steroidogenic Dehydrogenases and Reductases
3β-Hydroxysteroid Dehydrogenase/Δ5→Δ4-Isomerases
17β-Hydroxysteroid Dehydrogenases
Steroid 5α-Reductases
3α-Hydroxysteroid Dehydrogenases
11β-Hydroxysteroid Dehydrogenases
Steroid Sulfonation
Pathways
Adrenal Steroidogenic Pathways
Gonadal Steroidogenic Pathways
The Backdoor Pathway to Dihydrotestosterone
Pathways to 11-Oxygenated Androgens
Androgen Synthesis in Prostate Cancer
References
Chapter (88)
88. Mineralocorticoids: Physiology, Metabolism, Receptors, and Resistance
88
Sodium Homeostasis
Potassium Homeostasis
Specificity-Conferring Enzymes
11β-Hydroxysteroid Dehydrogenase Type 2
Mineralocorticoid Receptors
Evolution
Structure
Genomic Versus Nongenomic Aldosterone Actions
Sodium Transport
Epithelial Sodium Channels
Na+/K+-ATPase
Potassium Transport
Hydrogen Ion Transport
Nonepithelial Tissues
Cardiovascular System
Central Nervous System
Summary and Future Directions
References
Chapter (89)
89. Glucocorticoid Receptors: Mechanisms of Action in Health and Disease
Glucocorticoid Receptors: Mechanisms of Action in Health and Disease
Introduction
Glucocorticoid Receptor Polymorphisms
Glucocorticoid Receptor Physiology
Immune System
Cardiovascular System
Central Nervous System
Hepatic Carbohydrate and Lipid Metabolism
Glucocorticoid Receptor Resistance
Summary and Future Directions
References
Chapter (90)
90. Adrenal Androgens, Adrenarche, and Adrenopause
Adrenal Androgens, Adrenarche, and Adrenopause
Adrenarche
The Adrenal Glands
The Fetal Adrenal Gland
Clinical Facets of Adrenarche
Adrenal Steroidogenesis
Adrenopause
Epidemiology/Associations with Dehydroepiandrosterone Sulfate Concentrations, Aging, and Cardiovascular Risks
Conclusion
References
Chapter (91)
91. Adrenal Pathology
Accessory or Heterotopic Adrenal Tissue
Adrenal Pathology
91
Adrenal Myelolipoma
Ectopic Thyroid Tissue
Ovarian Thecal Metaplasia
Adrenal Amyloidosis
Adrenal Calcification
Adrenal Cysts
Adrenal Infection and Abscess
Congenital Adrenal Hyperplasia
Adrenal Cytomegaly
Inflammatory Adrenalitis
Functional Approach In Adrenal Pathology
Pathological Correlates of Primary Aldosteronism
Pathological Correlates of Adrenal Cushing Syndrome
Pathological Correlates of Virilism/Feminization
Pathological Correlates of Catecholamine Excess
Confirmation of Adrenocortical and Medullary Origin
Confirmation of Functional Sites in Primary Aldosteronism
Diagnostic and Predictive Biomarkers of Adrenocortical Carcinoma
Molecular Immunohistochemistry in Pheochromocytoma
References
Chapter (92)
92. Adrenal Gland Imaging
Adrenal Gland Imaging
Adrenal Gland Imaging
Introduction
Adrenal Gland Anatomy
Adrenal Gland Imaging
Adrenal Gland Imaging
Arteriography and Adrenal Vein Sampling
Clinical Utility
Adenoma or Metastases
Benign Adrenal Lesions
Neoplastic Adrenal Lesions
Functional Imaging in Primary Hyperaldosteronism
Summary
References
Chapter (93)
93. Adrenal Insufficiency
Adrenal Insufficiency
93
Epidemiology of Adrenal Insufficiency
Pathogenesis of Adrenal Insufficiency
Clinical Features of Adrenal Insufficiency
Etiology
Primary Adrenal Insufficiency
Diagnosis of Adrenal Insufficiency
Adrenocorticotropic Hormone Stimulation Testing
Overnight Metyrapone Test
Insulin Tolerance Test
Adrenal Autoantibody Tests
Serum 17-Hydroxyprogesterone
Very Long Chain Fatty Acids
Adrenal Imaging
Treatment of Adrenal Insufficiency
Replacement of Dehydroepiandrosterone
Quality of Life in Adrenal Insufficiency
Adrenal Suppression
Adrenal Crisis
Treatment of Adrenal Crisis
Prevention of Adrenal Crises
The Need for Novel Treatments for Adrenal Insufficiency
References
Chapter (94)
94. Defects of Adrenal Steroidogenesis
94
Virilizing Forms of Congenital Adrenal Hyperplasia
21-Hydroxylase Deficiency
11β-Hydroxylase Deficiency
P450 Oxidoreductase Deficiency
3β-Hydroxysteroid Dehydrogenase Type 2 Deficiency
Nonvirilizing Forms of Congenital Adrenal Hyperplasia
17α-Hydroxylase/17,20 Lyase Deficiency
Diagnosis of 17α-Hydroxylase/17,20 Lyase Deficiency
Other Conditions Affecting Adrenal Steroid Synthesis
Aldosterone Synthase Deficiency
Glucocorticoid-Remediable Aldosteronism
Smith–Lemli–Opitz Syndrome
Differential Diagnosis
Medical Therapy of Congenital Adrenal Hyperplasia
Glucocorticoid Therapy
Mineralocorticoid Therapy
Sex Steroid Replacement
Antihypertensive Therapy
Management of Atypical Genitalia
Future Directions and Novel Therapies
Conclusion
References
Chapter (95)
95. Adrenal Genomics II: Familial and Sporadic Neoplasia
Adrenal Genomics II: Familial and Sporadic Neoplasia
Genetic Causes Of Adrenal Neoplasia
Adrenocortical Tumors
Pheochromocytoma
Summary And Future Directions
References
Chapter (96)
96. Primary Aldosteronism
Pathogenesis And Genetics
Primary Aldosteronism
96
Familial Forms of Primary Aldosteronism
Somatic Mutations in Unilateral Primary Aldosteronism
Somatic Mutations in Bilateral Adrenal Hyperplasia
Prevalence
Clinical Diagnosis
Symptoms and Signs of Primary Aldosteronism
Diagnostic Workup for Primary Aldosteronism
Treatment
Anchor 472
References
Chapter (97)
97. Adrenocorticotropic Hormone–Independent Cushing Syndrome
Adrenocorticotropic Hormone–Independent Cushing Syndrome
Pathophysiology––Molecular Genetics and Animal Models
Molecular and Genetic Causes of Cortisol-Producing Adrenocortical Lesions
Animal Models
Clinical Manifestations
Hormonal Evaluation
Unilateral Tumors
Adrenocortical Adenoma
Adrenocortical Cancer
Bilateral Adrenocortical Tumors
Micronodular Adrenal Hyperplasia and Primary Pigmented Nodular Adrenal Disease
Primary Macronodular Adrenal Hyperplasia
Medical Treatment with Steroidogenesis Inhibitors (Table 97.5)
Surgery
Perspectives
References
Chapter (98)
98. Adrenocortical Carcinoma
Adrenocortical Carcinoma
Diagnosis
Hormonal Evaluation
Imaging
Histopathology
Staging
Therapy (Fig. 98.3)
Surgery
Radiation Therapy
Medical Therapy
Mitotane
Cytotoxic Chemotherapy
Targeted Therapies
Immunotherapy
Follow-Up
References
Chapter (99)
99. Pheochromocytoma
Pheochromocytoma
Catecholamine Production, Secretion, And Metabolism
Who to Test According to Presentation
Signs and Symptoms
Differential Diagnosis
Multiple Endocrine Neoplasia Syndromes
Von Hippel–Lindau Syndrome
Neurofibromatosis Type 1
Succinate Dehydrogenase Gene Family
Less Common Hereditary or Other Causes
Biochemical Diagnosis Of Pheochromocytoma
Preanalytics and Analytics
Interpretative Considerations
Follow-Up Biochemical Testing
Anatomic Imaging
Differential Diagnosis
Functional Imaging
Metaiodobenzylguanidine Scintigraphy
Positron Emission Tomography
Medical Therapy and Preparation for Surgery
Postoperative Management
Special Presentations And Therapeutic Problems
Multifocal and Metastatic Pheochromocytoma/Paraganglioma
Pheochromocytoma in Pregnancy
Future Directions
References
Chapter (100)
100. Adrenal Surgery
Adrenal Surgery
100
Preoperative Evaluation
Clinical
Familial History and Genetic Testing
Biochemical Evaluation
Imaging
Fine-Needle Aspiration
Disease-Specific Decision-Making For Surgery
Benign Nonfunctional Adrenal Tumors
Myelolipomas
Adrenal Cysts
Biochemically Functional Adrenal Disorders
Hypercortisolism
Congenital Adrenal Hyperplasia
Bilateral Macronodular Adrenal Hyperplasia
Primary Aldosteronism
Androgen- and Estrogen-Secreting Tumors
Pheochromocytoma
Adrenocortical Carcinoma
Metastatic Disease to the Adrenal Gland
Surgical Approaches To The Adrenal Gland
Open Anterior Transabdominal
Right
Left
Open Posterior (Lumbotomy)
Laparoscopic Anterior Transabdominal
Right
Left
Laparoscopic Lateral Transabdominal Adrenalectomy
Right
Left
Robot-Assisted Adrenalectomy
Bilateral Adrenalectomy
Partial Adrenalectomy
Surgical Complications
Intraoperative Complications
Postoperative Complications
Complications and Operative Approach
Bilateral Adrenalectomy
Nelson Syndrome
Additional Considerations
Conclusion
References
Chapter (101)
101. Differences of Sex Development
Introduction To Sexual Development
Embryology
Gonadal Development (Sex Determination)
Development of Internal and External Genitalia (Sex Differentiation)
Genetic Pathways Of Sex Development And Their Variations
Genetic Pathways
Differences Of Sex Development
46,XX Differences of Sex Development
46,XY Differences of Sex Development
Sex Chromosome Differences of Sex Development
Syndromic Differences of Sex Development
Tools in Differences of Sex Development Evaluation
Initial Gender Assignment
Management of Differences of Sex Development
Acknowledgements
REFERENCES
Chapter (102)
102. Endocrinology of Sexual Maturation and Puberty
Gonadarche
Endocrinology of Sexual Maturation and Puberty
102
Adrenarche
Control Of The Onset Of Puberty
Genetics of Pubertal Onset
Timing of Puberty
Physical Changes Of Puberty
Boys
Girls
Additional Changes During Sexual Maturation
Changes in Body Composition and Bone Mineral Density
Changes in Sleep and Brain Development
Other Changes at Puberty
Laboratory Testing During Puberty
Summary
References
Chapter (103)
103. Endocrinology of Pubertal Disorders
Precocious Puberty
Variants of Precocious Puberty
Endocrinology of Pubertal Disorders
103
Premature Thelarche
Premature Pubarche
Pathologic Precocious Puberty
Central Precocious Puberty
Peripheral Precocious Puberty
Abnormalities of G Proteins
Abnormalities of Gonadotropin Receptors
Tumors
Gonadal Tumors
Adrenal Tumors
Germ Cell Tumors
Exogenous Sex Steroids
Hypothyroidism
Delayed Puberty
Definition
Benign Variants of Delayed Puberty
Constitutional Delay of Growth and Puberty
Pathologic Delayed Puberty
Hypothalamic-Pituitary Hypogonadism
Primary Hypogonadism
Treatment of Delayed Puberty
Girls
Boys
Conclusion
References
Chapter (104)
104. Transgender Healthcare
Transgender Healthcare
Overview
Goal-Driven Approach to Hormone Therapy
Physical––Feminizing
Physical––Masculinizing
Sexuality Changes
Sexuality Changes––Feminizing
Sexuality Changes––Masculinizing
Sexuality and Gender-Affirming Hormone Therapy
Reproductive System Changes––Feminizing
Reproductive System Changes––Masculinizing
Risks
Laboratory Monitoring Considerations
Summary
References
Chapter (105)
105. Gonadotropin Regulation and Androgen and Estrogen Physiology
Regulation Of Gonadotropin
The Gonadotropins
Gonadotropin-Releasing Hormone
Feedback on Gonadotropin Secretion by Sex Steroids
Metabolic Regulation of Gonadotropins
Regulation of Gonadotropins by Stress
Seasonal Regulation of Gonadotropin Secretion
Androgen Physiology
Biosynthesis of Testosterone and Other Androgens
Structure Activity Relationship in Steroidal Androgens
The Regulation of Testosterone Production by LH
Transport and Bioavailability
Testosterone Metabolism
Mechanisms of Testosterone’s Action
Estrogen Physiology
Endogenous Estrogens
Regulation of Estradiol Production
Estrogen Transport and Bioavailability
Estrogen Metabolism
Mechanisms of Estrogen Action
References
Chapter (106)
106. Hypogonadism: Pathogenesis, Diagnosis, and Treatment
Introduction
106
Pathogenesis
Primary Hypogonadism
Klinefelter Syndrome
Other Sex Chromosome Disorders
Cryptorchidism and Spermatogenic Failure
Congenital Anorchia
Acquired Anorchia
Orchitis
Gonadotoxic Cancer Treatment
Noonan Syndrome
Myotonic Dystrophy
Autoimmune Polyglandular Syndrome
Sickle Cell Disease
Secondary Hypogonadism
Congenital Isolated Hypogonadotropic Hypogonadism
Congenital Hypogonadotropic Hypogonadism in Complex Genetic Syndromes
Congenital Combined Pituitary Hormone Deficiency
Pituitary and Nonpituitary Tumors
Nontumorous Hypothalamic-Pituitary Diseases/Injuries
Drug-induced
Diagnosis Of Hypogonadism
Clinical Diagnosis
History
Examination
Laboratory Diagnosis
Testosterone
Treatment Of Hypogonadism
Testosterone Replacement Therapy
Indications
Testosterone Preparations
Parenteral Testosterone Preparations
Transdermal Testosterone Preparations
Efficacy
Contraindications and Adverse Events
Monitoring of Treatment
Indications
Gonadotropin Treatment
. LH-like preparations can stimulate Leydig cells (Table 106.6). Recombinant LH is expensive, has a very short half-life, and ha...
Gonadotropin-Releasing Hormone Treatment
Future Directions
References
Chapter (107)
107. Testosterone Deficiency: Aging and Chronic Disease
Testosterone Deficiency: Aging and Chronic Disease
References
Chapter (108)
108. Gynecomastia
Physiologic Forms of Gynecomastia
Newborn Gynecomastia
Pubertal Gynecomastia
108
Adult and Senescent Gynecomastia
Pathologic Forms of Gynecomastia
Related to Elevated Estrogen
Related to Testosterone Deficiency
Related to Estradiol/Testosterone Imbalance
Related to Modulatory Hormones
Other Causes
Uncertain Causes
Treatment and Prevention
References
Chapter (109)
109. Erectile Dysfunction
Introduction
Guidelines
109
Epidemiology
Psychogenic Erectile Dysfunction
Organic Erectile Dysfunction
Penile Physiology
Anatomy of the Penis
Hemodynamics of Penile Erection
Innervation of the Penis
Neurotransmitters and Pharmacology of Erection
Testosterone and Male Sexual Function
Discussing Sexual Health with Patients
History
Physical Examination
Laboratory Testing
Specialized Testing for Erectile Dysfunction (Table 109.6)
Treatment Of Erectile Dysfunction
Adaptive Sexuality
Lifestyle Modification
Mental Health
Vacuum Erection Device
Medical Therapy For Erectile Dysfunction
Herbal Supplements and Complementary Medicine
Phosphodiesterase Type 5 Inhibitors
Intracavernosal Injection Therapy
Urethral Prostaglandin Suppositories
Malleable Penile Prostheses
Inflatable Penile Prostheses
Penile Vascular Surgery
Additional Conditions Contributing To Male Sexual Dysfunction
Disorders of Ejaculation, Emission, and Orgasm
Peyronie Disease
Priapism
New Pharmacotherapeutics
Stem Cell Therapy
Low-Intensity Extracorporeal Shock Wave Therapy
Platelet-Rich Plasma
Conclusions
References
Chapter (110)
110. Misuse and Abuse of Anabolic Hormones
Misuse and Abuse of Anabolic Hormones
AAS: Use, Misuse, and Abuse
Use
Misuse
Abuse
History and Epidemiology of Anabolic Steroid Abuse
History of Anabolic Steroid Abuse
Epidemiology of Anabolic Steroid Abuse
Ergogenic Potential of Anabolic Steroids
Types and Patterns of Androgen Doping
Direct Doping
Indirect Doping
Detection of Androgen Doping
Detection of Compounds Used in Direct Androgen Doping
Evaluation Process of AAS Abuse in Elite Athletes
Assessment of Men Abusing AAS in the Clinics
Administration of Epitestosterone
Masking Agents
Cardiovascular
Reproductive
Gynecomastia
Hepatic
Musculoskeletal
Renal
Dermatologic
Neuropsychiatric and Behavioral
Dependence
Elite Athletes
General Public
Conclusion
References
Chapter (111)
111. Regulation of Spermatogenesis
The Seminiferous Tubules
The Intertubular Tissue
111
Postnatal Growth
Cellular Development and Organization for Functional Control
The Spermatogenic Epithelium
Sertoli Cells
Spermatogonia and Spermatogonial Stem Cells
The Spermatogonial Stem Cell Niche
Spermatogonial Differentiation and Its Control
Meiosis
Spermiogenesis: Emergence of Spermatozoa
Germ Cell Associations and the Spermatogenic Cycle
Spermatogenic Efficiency and Germ Cell Loss
Genetic Defects and Spermatogenesis
Epigenetics in the Male Germline
The Intertubular Compartment
Leydig Cells
Other Interstitial Cells
The Immunologic Environment of the Testis
Endocrine and Local Control of Spermatogenesis
Interactions Between the Testis, Hypothalamus, and Pituitary Gland
Control of Sertoli Cell Function
Sertoli Cells During Fetal and Postnatal Development
Control of Spermatogenesis: Challenges Ahead
References
Chapter (112)
112. Prevalence and Causes of Male Infertility
Prevalence and Causes of Male Infertility
Common Causes Of Male Infertility
Hypothalamic-Pituitary Disorders
Testicular Disorders With Spermatogenesis Defects
Sperm Motility, Morphology, Function, or Genetic Incompetence—Spermatogenesis Qualitative Defects
Ductal Obstruction or Dysfunction
Idiopathic Azoospermia, Oligozoospermia, Asthenozoospermia, and Teratozoospermia
Other Possible Contributing Factors To Male Infertiliy
Obesity
Environmental Factors: Endocrine Disruptors
Cigarette Smoking
Cell Phone
Scrotal Hyperthermia
Epigenetics And Male Infertility
Summary And Future Directions
References
Chapter (113)
113. Clinical Management of Male Infertility
Clinical Management of Male Infertility
Introduction
Health Considerations For Infertile Men
Evaluation of Male Infertility
History and Physical Examination
Semen Analysis
Further Investigations and Complete Evaluation
Endocrine Evaluation
Low Semen Volume
Postejaculatory Urinalysis
Transrectal Ultrasound
Oligospermia/Asthenospermia/Teratospermia
Semen Leukocytes and Screening for Genital Infection
Antisperm Antibodies (ASA)
Genetic Testing (see Chapter 112)
Sperm DNA Fragmentation
Other Genetic Anomalies
Azoospermia
Management of Male Infertility
Lifestyle Modifications
Hormone Optimization
Ejaculatory Dysfunction
Ejaculatory Duct Obstruction
Pyospermia
Immunological Infertility
Varicocele Repair
Vasal Reconstruction
Assisted Reproductive Techniques (ART)
Sperm Retrieval
Conclusion
References
Chapter (114)
114. Male Contraception
The Need for Male Contraception
Current Methods
Withdrawal
Male Condom
114
Vas Occlusion
Male-Directed Contraceptive Methods in Development
Hormonal Male Contraception
Other New Hormonal Agents for Male Contraception
Nonhormonal Targets for Male Contraception
Men’s Attitude and Acceptability of Male Contraception
Summary and Future Directions
References
Chapter (115)
115. Testicular Dysgenesis Syndrome and Testicular Tumors
Testicular Dysgenesis Syndrome and Testicular Tumors
Testicular Dysgenesis Syndrome
Epidemiology
Biological Evidence
Cryptorchidism
Classification
Embryology
Etiology
Prevalence
Treatment
Long-Term Effects
Hypospadias
Embryology
Etiology
Prevalence
Treatment
Long-term Effects
Minipuberty
Minipuberty in Healthy Infants
Minipuberty in Various DSD and TDS Conditions
Testicular Tumors
Classification
Testicular Germ Cell Tumors
Fertility Preservation and Long-Term Effects of Testicular Cancer
Sex Cord-Stromal Tumors of the Testis
Other Testicular Tumors
Conclusion
References
Chapter (116)
116. Benign Prostatic Hyperplasia and Prostate Cancer
Introduction
Benign Prostatic Hyperplasia
Diagnosis
116
Management and Treatment of BPH
Summary and Future Research
Prostate Cancer
Diagnosis and Detection of Localized Prostate Cancer
Management and Treatment of Localized Prostate Cancer
Diagnosis and Detection of Advanced Prostate Cancer
Management and Treatment of Advanced Prostate Cancer
Summary and Future Challenges
References
Chapter (117)
117 - The Menstrual Cycle and Disorders of Ovulation
THE MENSTRUAL CYCLE: AN INTRODUCTION
Overview of the Hypothalamic-­Pituitary-­Ovarian Axis
The GnRH Pulse Generator
Anterior Pituitary Gonadotropes and Regulation of Gonadotropin Secretion
Ovarian Folliculogenesis and Steroidogenesis
Mechanisms of Ovarian Feedback Control of GnRH and Gonadotropin Secretion
Uterine Events During the Menstrual Cycle
Integrated Physiology of the Menstrual Cycle
Luteal-­Follicular Transition
Follicular Phase
Midcycle Gonadotropin Surge and Ovulation
Luteal Phase
Neuroendocrine Mechanisms of Anovulation
Physiological Anovulation
Selected Causes of Pathological Anovulation
Conclusion
References
The Menstrual Cycle: An Introduction
Overview of the Hypothalamic-­Pituitary-­Ovarian Axis
The GnRH Pulse Generator
Anterior Pituitary Gonadotropes and Regulation of Gonadotropin Secretion
Ovarian Folliculogenesis and Steroidogenesis
Mechanisms of Ovarian Feedback Control of GnRH and Gonadotropin Secretion
Uterine Events During the Menstrual Cycle
Integrated Physiology of the Menstrual Cycle
Luteal-­Follicular Transition
Follicular Phase
Midcycle Gonadotropin Surge and Ovulation
Luteal Phase
Neuroendocrine Mechanisms of Anovulation
Physiological Anovulation
Selected Causes of Pathological Anovulation
Conclusion
Chapter (118)
118 - Folliculogenesis, Ovulation, and Luteogenesis
Folliculogenesis
Folliculogenesis, Ovulation, and Luteogenesis
118
Preantral Follicles
Antral or Graafian Follicles
Oocyte Maturation Following the LH Surge
Luteinization
Luteolysis
Conclusion
References
Chapter (119)
119 - Ovarian Hormone Synthesis
Ovarian Hormone Synthesis
119
Acquisition of Cholesterol
The Cholesterol Side-­Chain Cleavage Reaction
Synthesis of Androgens
Synthesis of Estrogens
Steroid Hormone Metabolites
MicroRNA Regulation of Steroidogenic Enzymes
Peptide Hormones and Growth Factors Produced by the Ovary
Transforming Growth Factor-­β Superfamily
Relaxin
Gonadotropin Control of Ovarian Steroid Production
Follicle-­Stimulating Hormone and Luteinizing Hormone
Mechanisms of Gonadotropin Action
Other Hormones with Possible Actions in the Ovary
Intraovarian Regulators
Cholesterol Precursors
Role of Estrogens
Role of Androgens
Role of Progesterone
Transforming Growth Factor-­β Superfamily
Eicosanoids
Insulin-­Like Growth Factors and Their Binding Proteins
Other Intraovarian Regulators
Hormone Production During the Ovarian Life Cycle
The Fetal and Prepubertal Ovary
The Ovary During Reproductive Life
Endocrine Activity of the Postmenopausal Ovary
Conclusion
References
Chapter (120)
120. Estrogen and Progesterone Action
120
Nuclear Receptor Structure
Coactivators and Corepressors
Coactivators
Corepressors
Mechanisms of Estrogen Action
Estrogen Receptor Ligands
Estrogen Receptor Structure
Estrogen Receptor-Coactivator Interactions
Molecular Mechanisms of Estrogen Receptor Action
Mechanisms of Progesterone Action
Progesterone Receptor Isoforms
Molecular Mechanisms of Progesterone Action in the Endometrium and on Blastocyst Implantation
Conclusions
References
Chapter (121)
121. Contraception
Contraception
121
Drug Interactions
Medical Eligibility Criteria
High-Effectiveness Methods
Intrauterine Devices
Progestogen-Only Implant
Medium Effectiveness Methods
Progestogen-Only Injectable
Combined Hormonal Contraception
CHC Pill
CHC Patch and Vaginal Ring
Progestogen-Only Pill
Low Effectiveness Methods
Condoms
Diaphragm and Cap
Fertility Awareness-Based Methods
Lactational Amenorrhea
Sterilization
Emergency Contraception
Non-Contraceptive Benefits of Contraception
Summary and Future Directions
References
Chapter (122)
122. Menopause and Perimenopause
Menopause and Perimenopause
Staging Reproductive Aging
Late Reproductive Stage (Stage –3)
Menopausal Transition
Menopause
Postmenopause
Epidemiology (TABLE 122.1)
Age of Menopause
Population-Level Determinants of Menopause
Determinants of Early Menopause and Primary Ovarian Insufficiency
Pathophysiology Of Menopause
Ovarian Follicle Depletion—Current State of Knowledge
Follicular Growth Activation and Atresia
Ovarian and Pituitary Hormones
Clinical Presentation
The “Core Four” Symptoms: Hot Flashes, Vaginal Dryness, Adverse Mood, and Poor Sleep
Vasomotor Symptoms (Hot Flashes and Night Sweats)
Vaginal Dryness
Adverse Mood
Sleep Disturbances
Other Symptoms
Reproductive And Somatic Aging
Hypothalamic-Pituitary-Ovarian Axis
Somatotropic Axis
Thyroid
Adrenal
Bone
Cognition
Cardiovascular
Estrogen-Dependent Disorders
Diagnosis
Treatment
Hormone Therapy Overview
Vasomotor Symptoms
Urogenital Symptoms (GSM)
Sleep Disturbances
Adverse Mood
Other Common Issues
Complementary and Alternative Medicine in the Treatment of Menopausal Symptoms
Long-Term Use for Prevention of Chronic Conditions
Cancer Risks and Mitigation of Risk With Hormone Therapy
Summary
References
Chapter (123)
123. Female Infertility: Evaluation and Management
Female Infertility: Evaluation and Management
Introduction
History
Epidemiology
Pathogenesis And Clinical Features
Ovulatory Dysfunction
Anatomic Dysfunction
Ovarian Aging
Unexplained Infertility
Assessment of the Normal Menstrual Cycle
Assessment of Anatomic Dysfunction
Assessment of Cervical Mucus–Sperm Interaction
Assessment of Ovarian Aging
From Diagnosis to Prognosis
Ovarian Stimulation
Intrauterine Insemination
In Vitro Fertilization
Summary And Future Developments
References
Chapter (124)
124. Androgen Excess Disorders in Women
Androgen Excess Disorders in Women
Androgen Physiology and Pathophysiology
Androgen Biosynthesis
Regulation of Androgen Secretion
Blood Levels and Transport of Androgens
Mechanisms of Androgen Action
Clinical Manifestation of Androgen Excess
Cutaneous Manifestations
Polycystic Ovary and Polycystic Ovary Morphology
Metabolic Dysfunction
Common Androgen Excess Disorders
Polycystic Ovary Syndrome
Ovarian Neoplasms
Other Ovarian Hyperandrogenic Disorders
Congenital Adrenal Hyperplasia
Other Adrenal Hyperandrogenic Disorders
Idiopathic Hyperandrogenism
Diagnosis of Hyperandrogenism
Clinical Hyperandrogenism
Biochemical Hyperandrogenism
Treatment of Polycystic Ovary Syndrome and other Androgen Excess Disorders
Androgen Suppression
Ovulation Induction and Assisted Reproduction
Prevention of Long-Term Complications
Summary and Future Directions
References
Chapter (125)
125. Endometriosis
Pathogenesis
Endometriosis
125
Genetic Basis
Environment
Somatic Mutations
Pathophysiology
Cell Survival and Adhesion
Matrix Degradation And Invasion
Cell Growth and Neoangiogenesis
Altered Endocrine Activity
Immunity and Inflammation
Mechanisms Underlying Pain and Infertility
Diagnosis
Therapies
Medical
Surgical
Integrated Approach to the Patient With Endometriosis
Endometriosis-Associated Cancer Risk
Summary
References
Chapter (126)
126. Uterine Fibroids and Adenomyosis
Introduction
Epidemiology and Classification
Uterine Fibroids and Adenomyosis
126
Pathogenesis
Diagnosis
Therapies
Adenomyosis
Overview
Epidemiology and Classification
Pathogenesis
Diagnosis
Treatment
Summary
References
Chapter (127)
127. Hormonal Control of the Breast*
Hormonal Control of the Breast*
Adolescence
Anchor 466
The Mature Breast
Nulliparous Women
Parous Women
The Menopausal Breast
References
Chapter (128)
128. Sexual Dysfunction in the Female
Sexual Dysfunction in the Female
Normal Female Sexual Response
Neurotransmitters of Desire and Arousal
Endocrinology of Desire and Subjective Arousal
Endocrinology of Objective Arousal
Normal Vulvar and Vaginal Anatomy and Role of Hormones
Pathophysiology of Female Sexual Dysfunction
Hypoactive Sexual Desire Disorder
Sexual Arousal Disorders
Orgasmic Disorder
Sexual Pain Disorders
Treatments For Sexual Dysfunction
Hypoactive Sexual Desire Disorder
Nonhormonal Treatments
Hormonal Management of Hypoactive Sexual Desire Disorder
Genital Arousal and Sexual Pain
Persistent Genital Arousal Disorder
Conclusion
References
Chapter (129)
129. Hormonal Control of Human Pregnancy and Parturition
Preparation of the Endometrium
Embryo Competency
Hormonal Control of Human Pregnancy and Parturition
129
Decidualization of the Endometrium
Implantation and Placentation
Immune Tolerance of the Conceptus
Pregnancy Maintenance
Chorionic Gonadotropin
Gonadotropin-Releasing Hormone
Proopiomelanocortin-Derived Hormones
Corticotropin-Releasing Hormone
Placental Lactogen and Placental Growth Hormone
Modulation of Maternal Energy Homeostasis
Growth Factors and Cytokines
Steroid Hormones
Parturition and Birth Timing
Evolutionary Perspective
Fetal Maturation
Progesterone Withdrawal
Stress and Tissue-Level Inflammation
Progestin Therapy to Prevent Preterm Birth
Estrogens
Conclusion/Future Directions
References
Chapter (130)
130. Fetal and Neonatal Endocrinology
Fetal and Neonatal Endocrinology
Overview
Ectopic Fetal Hormone Production
The Hypothalamic-Pituitary Systems
Fetal Adrenal
Fetal Thyroid
The Fetal Autonomic Nervous System
Fetal Pancreas and Glucose Homeostasis
Fetal Parathryoid and Bone Metabolism
Parathyroid Development
Fetal Calcium and Phosphate Metabolism
Regulation of Calcium Homeostasis by PTH/PTHrP
Fetal Growth
Insulin-Like Growth Factors
Insulin
Fibroblast Growth Factor
Other Growth Factors and Signaling Pathways
Cortisol-Mediated Adaptations
Catecholamine-Mediated Adaptations
BAT Thermogenesis
Glucose Homeostasis
Calcium Homeostasis
Other Hormonal Adaptations
Future Directions
References
Chapter (131)
131. Hormonal Changes and Pregnancy Testing
Hormonal Changes and Pregnancy Testing
Introduction
Pituitary Gland
Hypopituitarism
Prolactin
Changes in Prolactin Physiology
Prolactinomas in Pregnancy
The Effect of Pregnancy on a Preexisting Prolactinoma
The Effect of Dopamine Agonists on a Developing Fetus
Prolactin and Antipsychotic Medication
Breastfeeding and Prolactin
Growth Hormone
Changes in GH Physiology During Pregnancy
GH Deficiency
GH Excess
Vasopressin
Thyroid Gland
Thyroid Hormones and Thyroid Regulation
Hyperthyroidism
Hypothyroidism
Adrenal Gland
Regulation of Glucocorticosteroid Synthesis
Parathyroid Glands
Regulation of Calcium During Pregnancy
Parathyroid Hormone–Related Protein
Vitamin D Deficiency
Hypercalcemia
Conclusion
References
Chapter (132)
132. Autoimmune Polyglandular Syndromes
Background
The Basis of Autoimmune Disease
The Normal Immune Response
Self-Tolerance
Central Tolerance
Peripheral Tolerance
Pathogenesis of Autoimmune Disease
Autoimmune Polyglandular Syndrome Type 1
Definition
Pathogenesis
Clinical Features
Chronic Mucocutaneous Candidiasis
Hypoparathyroidism
Adrenal Insufficiency
Gonadal Insufficiency
Other Endocrinopathies
Gastrointestinal Manifestations
Ectodermal Manifestations
Other Manifestations
Natural Course and Mortality
Diagnosis and Management
Autoimmune Polyglandular Syndrome Type 2
Definition
Pathogenesis
Clinical Features and Diagnosis
Management
References
Chapter (133)
133 - Multiple Endocrine Neoplasia Type 1
CLINICAL FINDINGS AND TREATMENT
Parathyroid Tumors
Pancreatic Tumors
Pituitary Tumors
Associated Tumors
Carcinoid Tumors
Other Clinical Considerations
MOLECULAR GENETICS
The MEN1 Gene
MEN1 Germline Mutations
MEN1 Germline Coding Variants
MEN1 Somatic Mutations
MEN1 Phenocopies and Mutations in Other Genes
MEN1 Mutational Analysis in Clinical Practice
SURVEILLANCE OF INDIVIDUALS AT RISK OF MULTIPLE ENDOCRINE NEOPLASIA TYPE 1 TUMORS
FUNCTION OF THE MULTIPLE ENDOCRINE NEOPLASIA TYPE 1 PROTEIN, MENIN, AND FUTURE TARGETED TREATMENTS
CONCLUSION
REFERENCES
Chapter (134)
134. Multiple Endocrine Neoplasia Types 2 and 3, and Medullary Thyroid Carcinoma
Multiple Endocrine Neoplasia Types 2 and 3, and Medullary Thyroid Carcinoma
Prevalence and Epidemiology
RET Structure and Function
RET Ligands
Functional Effects of RET Variants
Histology
C-Cells
C-Cell Hyperplasia
Clinical Relevance of Germline Ret Variants in Multiple Endocrine Neoplasia Type 2 and Multiple Endocrine Neoplasia Type 3
Multiple Endocrine Neoplasia Type 2 and Familial Medullary Thyroid Carcinoma
Multiple Endocrine Neoplasia Type 3
Specific Genotype-Phenotype Correlations
Clinical Presentation
Medullary Thyroid Carcinoma
Pheochromocytoma
Hyperparathyroidism
Screening in Multiple Endocrine Neoplasia Type 2 and Multiple Endocrine Neoplasia Type 3
Biochemical Screening
Genetic Screening
Management Implications of Genetic Results
Timing and Benefits of Prophylactic Thyroidectomy
Strategy and Extent of Thyroidectomy
The Role of Somatic Mutations
Sporadic Medullary Thyroid Carcinoma
Low-Penetrance Phenotypes
Hereditary Medullary Thyroid Carcinoma
Germline Screening
Sporadic Medullary Thyroid Carcinoma
Staging of Medullary Thyroid Carcinoma
Pheochromocytoma
Hyperparathyroidism
Management Of Medullary Thyroid Carcinoma
Localized Medullary Thyroid Carcinoma
Recurrent Medullary Thyroid Carcinoma
Persistent and Metastatic Medullary Thyroid Carcinoma
Management of Pheochromocytoma
Management of Hyperparathyroidism
Conclusion
References
Chapter (135)
135. Neuroendocrine Tumor Syndromes
Neuroendocrine Tumor Syndromes
Introduction
Epidemiology
Etiology
Pathologic Classification and Prognosis
Laboratory Tests and Biomarkers
Imaging
Biopsy
Clinical Features of Functional net and Their Syndromes
Insulinoma
Gastrinoma
VIPoma
Glucagonoma
Somatostatinoma
PPoma
Serotoninoma
Carcinoid Syndrome
Surgical Resection
Ablation of Primary Pancreas Neuroendocrine Tumors
Hepatic Arterial Embolization
Selective Internal Radiation Therapy
Systemic Therapies
Palliative Symptom Management
Conclusion
References
Chapter (136)
136. Ectopic Hormone Syndromes
History
Theoretical Considerations
136
Theories of the Origin of Ectopic Hormones
Hormones in Small-Cell Lung Carcinoma
Ectopic Adrenocorticotropic Hormone Syndrome
The POMC Gene
Regulation of POMC Gene Expression
Ectopic Adrenocorticotropic Hormone Syndrome
Pro-Opiomelanocortin Processing
Diagnosis
Treatment
Diagnosis
Management
Humoral Hypercalcemia of Malignancy
Parathyroid Hormone–Related Protein
Hypercalcemia in Hematologic Malignancy
Diagnosis
Treatment
Oncogenic Osteomalacia
Non–Islet Cell Tumor Hypoglycemia
Diagnosis
Management
Other Pituitary Ectopic Hormones
Gonadotropins
Ectopic Gut Hormone Syndromes
Ectopic Renin Secretion
Acknowledgments
References
Chapter (137)
137. Endocrine-Disrupting Chemicals and Human Health
Endocrine-Disrupting Chemicals and Human Health
137
Health Effects of Environmental Chemicals
The Lessons of Lead
The Lessons of PCBs
The Lessons of Diethylstilbestrol (DES)
Windows of Susceptibility
Mechanisms of EDC Actions
Dose-Response Characteristics of EDCS
Chemical Exposures in the Human Population
Disease Trends and Effects of EDCs
Cancer
Thyroid Disruption
Neurobehavior
Emerging Issues
Endocrine Disruptors, the Epigenome, and Transgenerational Effects
Increasing Exposures Worldwide
Expanded List of Diseases Related to EDCs
Mixtures
E-Waste
Green Chemistry
Conclusion and Guidance for Clinicians
References