DeGroot's Endocrinology

Basic Science and Clinical Practice

8th Edition - September 29, 2022
Imprint: Elsevier
Editor: R. Paul Robertson
Language: English
Hardback ISBN:
9 7 8 - 0 - 3 2 3 - 6 9 4 1 2 - 4
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 6 9 4 1 4 - 8
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 6 9 4 1 3 - 1

Thoroughly updated to reflect today's recent advances in adult and pediatric endocrinology, DeGroot’s Endocrinology, 8th Edition, remains the comprehensive, international reference… Read more

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Thoroughly updated to reflect today's recent advances in adult and pediatric endocrinology, DeGroot’s Endocrinology, 8th Edition, remains the comprehensive, international reference of choice for today’s endocrinologists and fellows. A full peer review of the previous edition, conducted by a largely new group of renowned editors, was used to update this trusted, two-volume resource. In-depth coverage of both basic and clinical aspects of endocrinology and up-to-date information on the treatment and management of endocrine disorders are provided by a diverse group of expert contributors from six continents. A full-color format and helpful algorithms summarize clinical decision-making and practical approaches to patient management.

Cover image
Title page
Table of Contents
Copyright
Contributors
Preface
Volume 1
Part 1. Principles of Endocrinology and Hormone Signaling
1. Principles of Endocrinology
Definition and Scope of Endocrinology
Historical Perspectives
Principles of Hormone Action
Hormone Action Through Receptors
Role of the Clinical Endocrinologist
Major Unsolved Problems
2. Principles of Endocrine Measurements
Introduction and Brief History of Endocrine Assays
Overview of General Concepts
Competitive Binding Assays
Noncompetitive Immunoassays
Free Serum/Plasma Hormone Assays
Plasma Renin Assays
Structural Assays––Mass Spectrometry
Summary and Future Directions
3. Endocrine Rhythms, the Sleep-Wake Cycle, and Biological Clocks
Introduction
Endocrine Rhythms
Cell Clocks
The Sleep-Wake Cycle
Melatonin as the Biological Maker of the Night
Consequences of Rhythm Disturbance on Metabolic Health
Novel technology for the Study of Biological Rhythms
Summary
Conclusions
Part 2. Neuroendocrinology and Pituitary Disease
4. Prolactinomas and Disorders of Prolactin Secretion
History
Epidemiology
Pathogenesis
Pathology
Differential Diagnosis of Hyperprolactinemia
Diagnosis of Prolactinomas
Treatment
5. Hypopituitarism Including Growth Hormone Deficiency
History
Etiology of Hypopituitarism
Morbidity and Mortality
Clinical Features
Diagnosis and Endocrine Evaluation
Hormone replacement Therapy
Pregnancy
Patient Care–Multidisciplinary Approach and Patient Education
6. Acromegaly
Pathogenesis
Diagnosis
Management
Integrated Treatment Approach to the Management of Acromegaly
7. Cushing Disease
Epidemiology
Etiology of Cushing Disease
Pathophysiology
Clinical Features
Biochemical Diagnosis of Cushing Syndrome
Establishing Adrenocorticotropic Hormone–Dependency of Cushing Syndrome
Differential Diagnosis of Adrenocorticotropic Hormone–Dependent Cushing Syndrome
Treatment of Cushing Disease
Prognosis For Cushing Disease: Persistent Morbidity and Mortality
Special Conditions
Future Directions
8. Clinically Nonfunctioning Sellar Masses
Types of Clinically Nonfunctioning Sellar Masses
Clinical Presentations
Diagnosis
Treatment
9. Thyroid-Stimulating Hormone–Producing Pituitary Tumors
Introduction
Epidemiology
Etiopathogenesis and Pathology
Clinical Presentation
Differential Diagnosis
Investigation
Management
Conclusions
10. Pituitary Surgery
History and Recent Developments of Transsphenoidal Surgery
Surgical Indications and Goals of Surgery
Preoperative Management
Surgical Technique
Acute postoperative Management And Early Observation Postdischarge
Outcomes After Transsphenoidal Pituitary Adenoma Surgery
Major Complications
Resection And Remission rates
Pituitary Centers Of Excellence
Conclusion
11. Craniopharyngiomas and Parasellar Masses
Types of Parasellar Masses
Craniopharyngiomas
Clinical Manifestations and Pituitary Function At Presentation
Long-Term Morbidity and Mortality
Rathke’s Cleft Cysts
Meningiomas
Chordomas
Gliomas
Germ Cell Tumors
Langerhans Cell Histiocytosis
Hamartomas
Pituitary Metastasis
12. Disorders of Sodium, Diabetes Insipidus and Hyponatremia
Introduction
Physiology of Sodium and Water Homeostasis
Diabetes Insipidus
Hyponatremia
The Syndrome of Inappropriate Antidiuresis
Treatment of Hyponatremia
Conclusions
13. Anatomy and Physiology of the Hypothalamus and Pituitary
Anatomy of the Hypothalamus
Anatomy and Histology of the Pituitary
Conclusions and Future Directions
14. Genetic Disorders of the Pituitary
Introduction
Familial Isolated Pituitary Adenoma
Syndromic Pituitary Tumors
Somatic Mutations in Pituitary Tumors
Criteria for Genetic Screening and Clinical Monitoring
Conclusion
CHAPTER 15. Aggressive Pituitary Tumors
Definitions
Epidemiology
Predictive Factors of Aggressiveness
Treatment
Conclusion
16. Radiotherapy in Pituitary Tumors
Introduction
Indications for Pituitary Radiotherapy
Radiotherapy Techniques and Fractionation
Clinical Outcomes of Pituitary Radiotherapy
Efficacy of Radiotherapy
Toxicity of Radiotherapy
Summary
Reirradiation
Conclusions and Future Directions
17. Somatic Growth and Maturation: Growth Hormone and Other Growth Factors
Introduction
Evaluation of Children With Short Stature
Evaluation of Children With Tall Stature
Endocrine Causes of Tall Stature
Conclusions
18. Growth Hormone Deficiency in Children
Introduction
Epidemiology
Pathogenesis
Clinical Features
Diagnosis Of Growth Hormone Deficiency In Childhood
Treatment
Conclusions
Part 3. Obesity and Nutrition
19. Basic and Clinical Appetite Regulation and Energy Expenditure
Introduction
Components of Eating Behavior
Components of Energy Expenditure
Body Weight Regulation
Conclusions
20. Obesity: isk, Risk Factors, and Medical Management
Prevalence of Overweight and Obesity
Social and Environmental Contributions to Obesity
Diseases Associated With Obesity
Therapy for Obesity
21. Genetic Syndromes Associated With Obesity
Introduction
Monogenic Obesity Syndromes
Pleiotropic Obesity Syndromes
Rare Variants Associated with Obesity
Conclusions
22. Regulation of Intermediary Metabolism During Fasting, Feeding, and Exercise
Postabsorptive Intermediary Metabolism
Prandial And Postprandial Intermediary Metabolism
Protein And Amino Acid Metabolism
Exercise Metabolism
Summary And Concluding Remarks
23. Adipose Tissue Function: Metabolic and Endocrine
Obesity And Its Health Consequences
Adipogenesis And Its Regulation
Immunometabolism: Its Regulation And Role In Insulin Resistance, Inflammation, And Disease
Lipid Metabolism In White Adipose Tissue
Human Brown Adipose Tissue––Brown Or Beige?
Adipose Tissue Endocrine Functions And Changes In Obesity
Adipose Tissue As A Therapeutic Target
24. Lipodystrophy Syndromes
Lipodystrophies: Definition and Diagnosis
Pathophysiology of Lipodystrophy
Classifications of Lipodystrophies and Their Clinical Manifestations
Mechanisms Responsible for Severe Insulin Resistance
Treatment of Syndromes of Lipodystrophies
Future Perspectives
25. Lipoprotein Metabolism and the Treatment of Lipid Disorders
Lipoprotein Metabolism
Disorders of Lipid Metabolism In Patients With Diabetes
Genetic Basis of Lipid Disorders
Diagnosis of Lipid Disorders
Management/Treatment
26. Metabolic Syndrome
Diagnosis and Prevalence
History
Diagnosis
Coronary Heart Disease and Type 2 Diabetes
Linkage of Metabolic Syndrome to Other Disorders
Treatment of Metabolic Syndrome
Children and Adolescents
Low Birth Weight Infants (Epigenetic Changes)
The Thrifty Genotype and the Increasing Incidence of Metabolic Syndrome
27. Bariatric Procedures and Operations
Introduction/Overview
Commonly Performed Bariatric Operations
Evolving Evidence Profile For The Use Of Endoscopic Bariatric And Metabolic Therapies In Clinical Practice
The Physiology Of Weight Loss After Bariatric Operations And Procedures
Physiologic Effects Of Bariatric Surgery On Cardiometabolic Health And Mortality
Impact Of Bariatric Surgery On Other Obesity-Related Comorbid Conditions (Table 27.1)
Complications Of Bariatric Operations And Procedures (Table 27.2)
Late and Chronic Complications
Weight Regain
Dumping Syndrome
Summary
Part 4. Diabetes Mellitus
28. Development of the Endocrine Pancreas
Pancreas Morphogenesis
Early Organ Specification And Bud Formation
Cell Type Differentiation
The Role Of Pancreatic Development In Human Diabetes
29. Regulation of Islet Hormone Synthesis and Secretion
Introduction
Hormonal Synthesis
Hormonal Secretion and Action
30. Mechanisms of Insulin Action
Introduction
Insulin
The Insulin Signaling Cascade
Heterologous Regulation of Insulin Signaling Cascades
Mouse Genetics Reveal Tissue-Integrated Insulin Signaling
Insulin Resistance and Metabolic Disease
31. Classification and Diagnosis of Diabetes Mellitus
Definition
Classification
Diagnosis
What’s New?
32. Autoimmune (Type 1) Diabetes Mellitus: Etiology, Pathogenesis, Prediction, and Prevention
Definition
Epidemiology
Inheritance
Natural History and Disease Staging
Etiology
Pathogenesis
Diagnostic Criteria
Prediction
Prevention
Primary Prevention
Secondary Prevention
Intervention
Summary and Future Directions
33. Type 2 Diabetes Mellitus: Etiology, Pathogenesis, and Natural History
Introduction
Epidemiology
Origins of the Disease: Etiologic Factors
Natural History of Diabetes as an Evolving Glucoregulatory Defect
The Pathophysiology of Insulin Resistance
The Molecular Basis of Human Insulin Resistance in Target Tissues
Cell Stress Responses, Nutrient Sensing, and Insulin Resistance
Syndromes of Severe Insulin Resistance
Natural History of Type 2 Diabetes as an End-Stage Manifestation of Cardiometabolic Disease
34. Diabetes Mellitus and Pregnancy
Diabetes and Pregnancy and the Mother
Diabetes and Pregnancy and the Offspring
Management of Diabetes in Pregnancy
Obstetric Management of Diabetes in Pregnancy
Long-Term Outcomes and Management of Gestational Diabetes
Summary and Future Directions
35. Hyperglycemia Secondary to Non-Traditional Diabetic Conditions
Hyperglycemia and Disorders of the Pancreas
Hyperglycemia Associated With Endocrinopathies
Drugs That can Cause Hyperglycemia
Lipid-Lowering Agents and New-Onset Diabetes Mellitus
Acquired Immunodeficiency Syndrome and Antiretroviral Drugs
Atypical Antipsychotic Agents
Conclusion
36. β Cell Glucose Toxicity and Oxidative Stress
Introduction
Normal Carbohydrate Biochemistry and Abnormal Glucose Metabolism Secondary to Chronic Hyperglycemia With Excess Generation of Reactive Oxygen Species
General Overview of Free Radical Biology and Antioxidants as Defense Mechanisms Against Elevated Cellular Generation of Reactive Oxygen Species
Evaluation of Oxidative Stress and Defective Endogenous Antioxidant Response In β Cells From The Points of View of the Glutathione and Thioredoxin Pathways
Brief Overview of the Contributions of Oxidative Stress to Secondary Complications of Diabetes
37. Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State
Diabetic Ketoacidosis
Hyperglycemic Hyperosmolar State
38. Hypoglycemia and Hypoglycemic Syndromes
Hypoglycemia
Physiology of Hypoglycemia
Counterregulatory Responses During Hypoglycemia
General Approach to the Patient
Hypoglycemia in Diabetes
Hypoglycemia in the Absence Of Diabetes
Hypoglycemia in Medicated or Ill Individuals
Hypoglycemia in Apparently Well Individuals
Neonatal Hypoglycemia
Conclusion and Future Directions
39. Treatment of Type 1 Diabetes Mellitus in Adults
Goals Of Management
Acute Complications
Chronic Complications
Quality Of Life
Team Approach To Management
Monitoring
Insulin Therapy
Nutrition
Other Therapies For Type 1 Diabetes
Future Perspectives
40. Clinical Management of Type 2 Diabetes Mellitus
Introduction
Diabetes Education
Nutrition
Summary
Physical Activity
Pharmacotherapy Of Type 2 Diabetes
Incretin-Based Therapies
Sodium-Glucose Cotransporter-2 Inhibitors
Insulin Therapy In Type 2 Diabetes
Practical Aspects For Managing Type 2 Diabetes
Diabetes Technology
Population Management
Conclusion
41. Pancreas and Islet Transplantation
Introduction
Pancreas Transplantation
Allogeneic Islet (Alloislet) Transplantation
Immunosuppressive Drugs
Autologous Islet (Autoislet) Transplantation
Effect of Successful Pancreas or Islet Transplantation on Complications of Diabetes
Future Directions and Conclusions
42. Diabetes and Long-Term Complications
History
Classification
Epidemiology
Pathophysiology
Role of Glucose Control in the Prevention of Diabetic Complications
Role of Glucose Control in the Prevention of Cardiovascular Disease
Can We Prevent Macrovascular Disease?
Effects of Specific Hypoglycemic Agents on Cardiovascular Disease and Renal Outcomes in Patients With Type 2 Diabetes
Conclusion
43. Diabetic Eye Disease
Pathogenesis
Natural History of Diabetic Retinopathy
Clinical Classification of Diabetic Retinopathy Severity
Epidemiology
Other Ocular Diseases Associated With Diabetes
Detection
Management
Novel Therapies
44. Diabetic Neuropathy
Definition of Diabetic Neuropathies
Classification of Diabetic Neuropathies
Distal Symmetrical Polyneuropathy
Distal Symmetric Polyneuropathy Evaluation in Clinical Research
Diabetic Autonomic Neuropathies
Atypical Neuropathies
Conclusions
45. Diabetic Kidney Disease
Epidemiology
Risk Factors
Diagnosis and Classification
Natural History
Structural Changes of the Kidney
Pathophysiology
Treatment
Summary and Future Directions
46. Diabetic Foot and Vascular Complications
Introduction
Pathophysiology
Presentation and Diagnosis
Medical Management
Surgical Management
Multidisciplinary Approach
Future Trends
Part 5. Parathyroid Gland, Calciotropic Hormones, and Bone Metabolism
47. Parathyroid Hormone and the Parathyroid Hormone Receptor Type 1 in the Regulation of Calcium and Phosphate Homeostasis and Bone Metabolism
Regulation Of Mineral Ion Homeostasis—General Considerations
Parathyroid Hormone
Parathyroid Hormone–Dependent Regulation Of Mineral Ion Homeostasis Mediated Through The Parathyroid Hormone Receptor Type-1
Molecular Properties Of The Parathyroid Hormone Receptor Type-1
The Parathyroid Hormone Receptor Type-2 And Tip39
Summary
48. Parathyroid Hormone-Related Protein
The Pthrp Gene And The Pth/Pthrp Gene Family
Posttranslational Processing Of Parathyroid Hormone-Related Protein
Parathyroid Hormone-Related Protein Receptors
Nuclear Parathyroid Hormone-Related Protein
Physiologic Functions Of Parathyroid Hormone-Related Protein
Parathyroid Hormone-Related Protein In Disease
Conclusion
49. Calcitonin
Calcitonin Synthesis, Secretion, and Cells of Origin
Calcitonin Chemistry
Calcitonin Gene
Calcitonin Receptors
Calcitonin Physiology
Peptides Related to Calcitonin
Calcitonin and its Receptors in Cancer
Calcitonin As a Therapeutic
Conclusion
50. Vitamin D: From Photosynthesis, Metabolism, and Action to Clinical Applications
Historic Overview
Origin of Vitamin D: Nutrition and Photosynthesis
Metabolism of Vitamin D
Vitamin D Transport
Action and Mode of Action
Clinical Consequences of Vitamin D Status
Clinical Use of Vitamin D
Summary
51. Bone Development and Remodeling
Mechanisms of Skeletal Development
Principles of Bone Remodeling and Skeletal Homeostasis
Cellular and Molecular Control of Skeletal Development and Bone Remodeling
Regulation of Bone Remodeling and Bone Mass
Conclusion
52. Regulation of Calcium Homeostasis and Genetic Disorders That Affect Calcium Metabolism
Regulation of Calcium Homeostasis
PTH Gene Structure and Function
Hypercalcemic Diseases
Hypocalcemic Disorders
Conclusion
53. Genetic Disorders of Phosphate Homeostasis
Regulation of Phosphate Homeostasis
Regulation of Phosphate Absorption
Fibroblast Growth Factor-23–Associated Syndromes
Possible Future Therapeutic Avenues
54. Primary Hyperparathyroidism
Introduction
Risk Factors, Pathology, and Anatomical Location
Epidemiology, Diagnosis, and Overview of Clinical Features
The Skeleton
Nephrolithiasis and Renal Function
Other Organ Involvement
Unusual Presentations
Evaluation
Natural History
Surgery
Medical Management
Hydrochlorothiazide
Summary
55. Malignancy-Associated Hypercalcemia
Introduction and History
Normal Physiology of Calcium Metabolism
Malignancy-Associated Hypercalcemia
Treatment
56. Surgical Management of Hyperparathyroidism
Primary Hyperparathyroidism
Special Circumstances in the Surgical Management of Primary Hyperparathyroidism
Secondary Hyperparathyroidism
Tertiary Hyperparathyroidism
COVID-19 and Parathyroid Surgery
Summary
57. Pseudohypoparathyroidism, Albright’s Hereditary Osteodystrophy, and Progressive Osseous Heteroplasia: Disorders Caused by GNAS Mutations that Reduce Gsα Activity
Diagnosis and Progression of Parathyroid Hormone Resistance
Pseudohypoparathyroidism Type-Ia
The Complex Gnas Locus
Clinically Distinct, Genetically Related Pseudohypoparathyroidism Variants
Pseudohypoparathyroidism Type-Ib
Pseudohypoparathyroidism Type-II
Acrodysostosis With Hormonal Resistance
Treatment
Summary
58. 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
Molecular Etiology of Vitamin D Hydroxylation–Deficient Rickets Type 1B
Treatment of Vitamin D Hydroxylation–Deficient Rickets, Type 1B
Molecular Etiology of Vitamin D Hydroxylation–Deficient Rickets Type 1A
Treatment of Vitamin D Hydroxylation–Deficient Rickets, Type 1A
Treatment OF Vitamin D-Dependent Rickets, Type 2A
Idiopathic Infantile Hypercalcemia
Treatment of Idiopathic Infantile Hypercalcemia
Future Directions
59. Hereditary Disorders of the Skeleton
Dense Bone Disorders
Osteogenesis Imperfecta and Heritable Osteoporoses
Paget Disease of Bone
Disorders of Increased RANK/OPG/RANKL/NF-ĸB Signaling
60. Osteoporosis
What Is Osteoporosis?
Origins of Skeletal Fragility
Epidemiology
Assessing Patients at Risk of Fracture
Treatment Decisions
Management of Subtypes of Osteoporosis
61. CKD-MBD Syndrome: Chronic Kidney Disease Produced Disorders in Skeletal, Vascular, and Cardiac Tissues and Mineral Metabolism
Pathobiology
Pathogenesis
Pathogenic Factors in the Chronic Kidney Disease–Mineral and Bone Disorder
Pathology of Renal Osteodystrophy
Associated Features
Conclusion
62. Disorders of Mineralization
Mineralization
Clinical Features of Rickets and Osteomalacia
Radiologic Features
Nutritional Osteomalacia and Rickets
Gastrointestinal Diseases
Disorders of Vitamin D Metabolism
Hypophosphatemia
Miscellaneous Causes of Impaired Mineralization
Treatment
Conclusion
63. Paget Disease of Bone
Incidence and Epidemiology
Pathophysiology
Clinical Features
Biochemical Features
Systemic Complications and Associated Diseases
Drug Treatment
Treatment and Posttreatment Laboratory Evaluation
Volume 2
Part 6. Thyroid
64. Anatomy and Development of the Thyroid
The Anatomy Of The Thyroid Gland
Thyroid Follicular Cells And Thyroid Follicles
Other Thyroid Cells
The Development Of The Thyroid Gland
Molecular Genetics Of Thyroid Gland Development
Phylogenesis Of The Thyroid Gland
65. Thyroid-Stimulating Hormone and TSH Receptor
Introduction
Regulation of Thyroid-Stimulating Hormone Biosynthesis
Regulation of Thyroid-Stimulating Hormone Secretion
Thyrostimulin
Thyroid-Stimulating Hormone Receptor
Thyroidal Actions of Thyroid-Stimulating Hormone
Thyroid-Stimulating Hormone Receptor/Insulin-Like Growth Factor 1 Receptor Crosstalk
Extrathyroidal Actions Mediated By Thyroid-Stimulating Hormone Receptor
66. Thyroid Hormone Transporters and Metabolism
Thyroid Hormone Transport And Metabolism
Disorders Of Thyroid Hormone Transport
Disorders Of Thyroid Hormone Metabolism
67. Thyroid Hormone Action
Components Of Thyroid Hormone Action
Regulation Of Ligand Availability In Development And The Adult
Thyroid Hormone Binding To Serum Proteins
Local Regulation Of Thyroid Hormone Availability
Thyroid Hormone Receptors And Their Response Elements
Positive And Negative Gene Regulation By Thyroid Hormone
Nongenomic Thyroid Hormone Action
Thyroid Hormone Tissue-Specific Actions
Lessons From Resistance To Thyroid Hormone Receptor Beta And Alpha
Summary And Future Directions
68. Thyroid Function Testing (Thyrotropin, Triiodothyronine, and Thyroxine)
Introduction
Thyrotropin
Free Thyroid Hormones
Total Thyroxine And Triiodothyronine
Interference In The Measurement Of Thyroid Hormones
Future Directions
69. Thyroid Imaging
Ultrasonography
Primary Thyroid Lymphoma
Scintigraphy
Computed Tomography And Magnetic Resonance Imaging
Incidentalomas
Future Directions
70. Pathology of the Thyroid Gland
Thyroid Gland
Pathologic Assessment Of Thyroid Lesions
Tumors With Thymic Or Related Branchial Pouch Differentiation
Rare Tumors of Thyroid Gland
Summary and Future Directions
71. Graves Disease
Historical Background
Etiology
Pathology
Pathogenesis
Clinical Spectrum
Diagnosis
Management
Antithyroid Drugs
Radioactive Iodine
Thyroidectomy
Perspective and Conclusion
72. Graves’ Orbitopathy
Epidemiology
Risk Factors
Pathogenesis
Clinical Manifestations And Diagnosis
Management
Brief Note On Graves Dermopathy And Thyroid Acropachy
Summary And Perspectives
73. Thyroiditis
Introduction: Concept and Definition of Thyroiditis
Subtypes of Thyroiditis
Hashimoto’s Thyroiditis
Hashimoto’s Thyroiditis and Thyroid Malignancy
Acute/Infectious Thyroiditis
Subacute Thyroiditis
Silent Thyroiditis
Riedel’s Thyroiditis
IgG4 Thyroiditis
Summary and Future Directions
74. Hypothyroidism
Brief History
Hypothalamic-Pituitary-Thyroid Axis
Thyroid Physiology and Thyroid Hormone Action
Epidemiology
Clinical Manifestations
Etiology
Diagnosis
Treatment
Summary and Areas of Future Research
75. Thyroid and Pregnancy
Thyroid Disease and Fertility
Maternal and Fetal Physiology in Pregnancy
Thyroid Function Tests in Pregnancy
Hyperthyroidism in Pregnancy
Hypothyroidism and Hypothyroxinemia In Pregnancy
Screening for Thyroid Dysfunction in Pregnancy
Thyroid Nodules and Cancer During Pregnancy
Thyroid Disorders in the Postpartum Period
Summary and Future Directions
76. Iodine Nutrition and the Thyroid
Dietary Sources Of Iodine
Metabolism
Methods To Assess Iodine Status
Effects of Iodine Deficiency on the Thyroid and Brain
Treatment And Prevention Of Iodine Deficiency
Iodine Excess
77. Euthyroid and Hyperthyroid Nodules and Goiter
Basic Aspects
Familial and Sporadic Nonautoimmune Hyperthyroidism
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
Treatment of Autonomous Thyroid Nodules
Treatment of Euthyroid Nodules (see Table 77.3)
78. Differentiated Thyroid Cancer – Streamlining Diagnosis and Optimizing Management
Epidemiology
Pathology
Follicular Thyroid Carcinoma
Hurthle Cell (Oncocytic) Tumors
Poorly Differentiated Thyroid Carcinoma
Causes
Diagnosis, Clinical Features, And Course
Staging, Risk Of Recurrence, And Response To Therapy
Prognostic Factors
Therapy And Monitoring
79. Medullary Thyroid Cancer
Introduction
Clinical Presentation And Diagnosis
Pathology And Pathogenesis
Initial Therapy
Postsurgical Follow-Up
Other Therapies
Conclusions
80. Anaplastic (Undifferentiated) Thyroid Carcinoma
Presentation
Diagnosis
Evaluation
Establish Goals of Care
Prognosis
Therapy
Future Directions
Conclusions
81. Resistance to Thyroid Hormone and Genetic Defects of the Thyroid
Thyroid Gland Development, Hormone Biosynthesis, and Action
Congenital Primary Hypothyroidism
Classification of Disorders of Thyroid Hormone Action
Differential Diagnosis of Elevated Thyroxine and/or Triiodothyronine with Nonsuppressed Thyroid-Stimulating Hormone
Resistance to Thyroid Hormone β
Resistance to Thyroid Hormone Alpha
82. Surgical Management of Thyroid Disease
History Of Thyroid Surgery
Relevant Surgical Anatomy
Imaging For Surgical Planning
Molecular Testing And Its Use For Surgical Planning
Diseases Of The Thyroid And Surgical Procedures To Consider
Developmental Abnormalities Of The Thyroid Gland And Their Surgical Management
Thyroid Cancer And The Surgical Management
Indications For Surgery Of The Thyroid Gland
Transoral Approach To Thyroidectomy
Open Surgical Techniques
Minimally Invasive Techniques
Surgical Complications
83. Nonthyroidal Illness Syndrome
Low Triiodothyronine States
Nonthyroidal Illness Syndrome with Low Serum Thyroxine
Serum Hormone Levels
Thyroid Hormone Transport
Thyroid Hormone Metabolism and Action
Tissue- and Organ-Specific Responses in Nonthyroidal Illness Syndrome
Mechanism of Altered Thyroid Hormone Metabolism in Nonthyroidal Illness Syndrome
Clinical Implications and Therapeutic Considerations
Conclusion
84. Drugs and Thyroid
Introduction
Drugs Affecting Hypothalamic-Pituitary Control Of The Thyroid
Drugs Affecting Thyroid Hormone Synthesis Or Secretion
Drugs That Enhance Thyroid Autoimmunity
Drugs Causing Direct Thyroid Damage
Drugs Affecting Protein Binding Of Thyroid Hormone
Drugs Affecting Thyroid Hormone Activation, Metabolism, And Excretion
Drugs Affecting The Absorption Of Thyroid Hormone Preparations
Drugs Causing Abnormal Thyroid Testing In Euthyroid Patients
The Effect Of Thyroid Dysfunction On Drug Metabolism
Summary And Future Directions
Part 7. Adrenal
85. Adrenal Development and Homeostasis
Introduction and Historical Background
Adrenal Structure and Function
Embryonic Adrenal Development
Postnatal Adrenal Development
Maintenance of Adult Adrenal Cortex Function by Cortical Cell Renewal
Conclusion and Future Directions
86. Genetic Disorders of the Adrenal Cortex
Primary Adrenal Insufficiency: An Overview
Genetic Disorders of the Adrenal Cortex
Conclusion
87. Enzymes and Pathways of Human Steroidogenesis
Overview of the Human Steroidogenic Enzymes and Steroidogenesis
Human Steroidogenic Cytochrome P450 Enzymes
Redox Partner Proteins
Steroidogenic Dehydrogenases and Reductases
Steroid Sulfonation
Pathways
88. Mineralocorticoids: Physiology, Metabolism, Receptors, and Resistance
Feedback Control of Aldosterone Secretion
Sodium Homeostasis
Potassium Homeostasis
Specificity-Conferring Enzymes
Mineralocorticoid Receptors
Cellular Mechanisms of Aldosterone Action
Nonepithelial Tissues
Summary and Future Directions
89. Glucocorticoid Receptorse: Mechanisms of Action in Health and Disease
Introduction
Glucocorticoid Receptor Domain Organization
Glucocorticoid Receptor Regulation of Transcription
Glucocorticoid Receptor Polymorphisms
Glucocorticoid Receptor Isoforms Derived From Single Gene
Glucocorticoid Receptor Posttranslational Modifications
Glucocorticoid Receptor Physiology
Glucocorticoid Receptor Ligands and Pulsatility
Glucocorticoid Receptor Resistance
Summary and Future Directions
90. Adrenal Androgens, Adrenarche, and Adrenopause
Adrenarche
The Adrenal Glands
The Fetal Adrenal Gland
Postnatal Adrenal Morphology and Function
Dehydroepiandrosterone and in Vitro Fertilization
Neurobiology of Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate
Conclusion
91. Adrenal Pathology
Anatomic Pathology in Developmental Abnormalities of the Adrenal Gland
Tumor-Like Lesions Of The Adrenal Gland
Functional Approach In Adrenal Pathology
Pathology In The Distinction Of Adrenocortical Carcinoma
Diagnostic And Predictive Immunohistochemical Biomarkers In Adrenal Pathology
Synoptic Reporting In Adrenocortical Carcinoma And Pheochromocytoma
92. Adrenal Gland Imaging
Introduction
Adrenal Gland Anatomy
Adrenal Gland Imaging
Clinical Utility
Summary
93. Adrenal Insufficiency
Brief Historical Perspective: the Changing Spectrum of Adrenal Insufficiency Etiology
Epidemiology of Adrenal Insufficiency
Pathogenesis of Adrenal Insufficiency
Clinical Features of Adrenal Insufficiency
Etiology
Critical Illness-Related Corticosteroid Insufficiency
Diagnosis of Adrenal Insufficiency
Treatment of Adrenal Insufficiency
Adrenal Crisis
94. Defects of Adrenal Steroidogenesis
Virilizing Forms of Congenital Adrenal Hyperplasia
Nonvirilizing Forms of Congenital Adrenal Hyperplasia
Other Conditions Affecting Adrenal Steroid Synthesis
Differential Diagnosis
Medical Therapy of Congenital Adrenal Hyperplasia
Future Directions and Novel Therapies
Conclusion
95. Adrenal Genomics II: Familial and Sporadic Neoplasia
Introduction
Genetic Causes Of Adrenal Neoplasia
Summary And Future Directions
96. Primary Aldosteronism
Pathophysiology
Pathogenesis And Genetics
Prevalence
Clinical Diagnosis
Treatment
97. Adrenocorticotropic Hormone–Independent Cushing Syndrome
Introduction
Epidemiology
Pathophysiology––Molecular Genetics and Animal Models
Diagnosis
Etiology
Management of Adrenal Cushing Syndrome
Perspectives
98. Adrenocortical Carcinoma
Epidemiology
Risk Factors And Genetics Of Adrenocortical Carcinoma
Clinical Presentation
Diagnosis
Staging
Therapy (Fig. 98.3)
Medical Therapy
Follow-Up
99. Pheochromocytoma
Introduction And History
Catecholamine Production, Secretion, And Metabolism
Clinical Presentation
Pathology
Genetics Of Pheochromocytoma
Biochemical Diagnosis Of Pheochromocytoma
Localization Of Pheochromocytoma
Management Of Pheochromocytoma
Special Presentations And Therapeutic Problems
Future Directions
100. Adrenal Surgery
Background And History
Preoperative Evaluation
Disease-Specific Decision-Making For Surgery
Surgical Approaches To The Adrenal Gland
Open Anterior Transabdominal
Open Flank–Transabdominal or Retroperitoneal
Open Posterior (Lumbotomy)
Laparoscopic Anterior Transabdominal
Laparoscopic Lateral Transabdominal Adrenalectomy
Laparoscopic Hand-Assisted Adrenalectomy
Lateral Retroperitoneoscopic Adrenalectomy
Posterior (Dorsal) Retroperitoneoscopic Adrenalectomy
Robot-Assisted Adrenalectomy
Thoracoabdominal Approach To Adrenalectomy
Disease-Specific Considerations And Decision For Extent OF Adrenalectomy
Bilateral Adrenalectomy
Partial Adrenalectomy
Disease-Specific Intraoperative Considerations
Disease-Specific Postoperative Care And Follow-Up
Conclusion
Part 8. Reproductive Endocrinology and Sexual Function
101. Differences of Sex Development
Introduction To Sexual Development
Embryology
Genetic Pathways Of Sex Development And Their Variations
Differences Of Sex Development
Evaluation And Management Of Differences Of Sex Development
Acknowledgements
102. Endocrinology of Sexual Maturation and Puberty
Endocrine Physiology Of Sexual Maturation
Control Of The Onset Of Puberty
Physical Changes Of Puberty
Pubertal Growth And The Growth Hormone/Insulin Growth Factor Axis
Additional Changes During Sexual Maturation
Laboratory Testing During Puberty
Summary
103. Endocrinology of Pubertal Disorders
Introduction
Precocious Puberty
Variants of Precocious Puberty
Pathologic Precocious Puberty
Tumors
Hypothyroidism
Delayed Puberty
Benign Variants of Delayed Puberty
Pathologic Delayed Puberty
Treatment of Delayed Puberty
Conclusion
104. Transgender Healthcare
Overview
Principles of Gender-Affirming Hormone Therapy
General Approach to Treatment––Feminizing
General Approach to Treatment––Masculinizing
Laboratory Monitoring Considerations
Summary
Part 9. Male Reproduction
105. Gonadotropin Regulation and Androgen and Estrogen Physiology
Regulation Of Gonadotropin
Androgen Physiology
Estrogen Physiology
106. Hypogonadism: Pathogenesis, Diagnosis, and Treatment
Introduction
Pathogenesis
Secondary Hypogonadism
Diagnosis Of Hypogonadism
Laboratory Diagnosis
Treatment Of Hypogonadism
Gonadotropin Induction Of Spermatogenesis And Fertility
Future Directions
107. Testosterone Deficiency: Aging and Chronic Disease
Aging
Acute and Chronic Disease
Medications
108. Gynecomastia
Physiologic Forms of Gynecomastia
Pathologic Forms of Gynecomastia
Treatment and Prevention
109. Erectile Dysfunction
Introduction
Guidelines
Epidemiology
Penile Physiology
Clinical Evaluation Of The Man With Erectile Dysfunction
Treatment Of Erectile Dysfunction
Medical Therapy For Erectile Dysfunction
Surgical Therapies For Erectile Dysfunction
Additional Conditions Contributing To Male Sexual Dysfunction
Future Directions For The Treatment Of Erectile Dysfunction
Conclusions
110. Misuse and Abuse of Anabolic Hormones
AAS: Use, Misuse, and Abuse
History and Epidemiology of Anabolic Steroid Abuse
Ergogenic Potential of Anabolic Steroids
Types and Patterns of Androgen Doping
Detection of Androgen Doping
Strategies Used by Athletes to Avoid Detection of Androgen Abuse
Health Consequences of Anabolic Steroid Abuse
Management Options of Anabolic Steroid Abuse
Conclusion
111. Regulation of Spermatogenesis
Macroscopic Organization of the Adult Human Testis
Cellular Development and Organization for Functional Control
The Intertubular Compartment
The Immunologic Environment of the Testis
Endocrine and Local Control of Spermatogenesis
Control of Sertoli Cell Function
112. Prevalence and Causes of Male Infertility
Introduction
Definition And Prevalence Of Male Infertility
Common Causes Of Male Infertility
Other Possible Contributing Factors To Male Infertiliy
Epigenetics And Male Infertility
Summary And Future Directions
113. Clinical Management of Male Infertility
Introduction
Health Considerations For Infertile Men
Management of Male Infertility
Conclusion
114. Male Contraception
The Need for Male Contraception
Current Methods
Male-Directed Contraceptive Methods in Development
Summary and Future Directions
115. Testicular Dysgenesis Syndrome and Testicular Tumors
Testicular Dysgenesis Syndrome
Cryptorchidism
Hypospadias
Minipuberty
Testicular Tumors
Conclusion
116. Benign Prostatic Hyperplasia and Prostate Cancer
Introduction
Benign Prostatic Hyperplasia
Prostate Cancer
Summary and Future Challenges
Part 10. Female Reproduction
117. The Menstrual Cycle and Disorders of Ovulation
The Menstrual Cycle: An Introduction
Overview of the Hypothalamic-Pituitary-Ovarian Axis
Integrated Physiology of the Menstrual Cycle
Neuroendocrine Mechanisms of Anovulation
Conclusion
118. Folliculogenesis, Ovulation, and Luteogenesis
Ovary Anatomy and Histology
Folliculogenesis
Ovulation
Luteogenesis
Conclusion
119. Ovarian Hormone Synthesis
Ovarian Steroid Hormone Biosynthesis
Peptide Hormones and Growth Factors Produced by the Ovary
Gonadotropin Control of Ovarian Steroid Production
Intraovarian Regulators
Hormone Production During the Ovarian Life Cycle
Conclusion
120. Estrogen and Progesterone Action
Interaction of Steroid Hormones With Target Cells
Nuclear Receptor Structure
Coactivators and Corepressors
Mechanisms of Estrogen Action
Mechanisms of Progesterone Action
Conclusions
121. Contraception
Contraceptive Use
Methods and Their Effectiveness
Drug Interactions
Medical Eligibility Criteria
Medium Effectiveness Methods
Low Effectiveness Methods
Summary and Future Directions
122. Menopause and Perimenopause
Mechanisms Of Menopause And The Transition
Staging Reproductive Aging
Epidemiology (TABLE 122.1)
Pathophysiology Of Menopause
Clinical Presentation
Reproductive And Somatic Aging
Diagnosis
Treatment
Summary
123. Female Infertility: Evaluation and Management
Introduction
History
Epidemiology
Pathogenesis And Clinical Features
Evaluation Of The Female In The Infertile Couple
Expectant Management Of The Infertile Couple
Summary And Future Developments
124. Androgen Excess Disorders in Women
Androgen Physiology and Pathophysiology
Clinical Manifestation of Androgen Excess
Common Androgen Excess Disorders
Diagnosis of Hyperandrogenism
Treatment of Polycystic Ovary Syndrome and other Androgen Excess Disorders
Summary and Future Directions
125. Endometriosis
Epidemiology
Pathogenesis
Pathophysiology
Diagnosis
Therapies
Summary
126. Uterine Fibroids and Adenomyosis
Uterine Fibroids
Adenomyosis
127. Hormonal Control of the Breast
Hypothalamic-Pituitary Influences, Ovarian Function, And Breast Development
The Mature Breast
Distribution Pattern Of Estrogen Receptor– And Progesterone Receptor–Positive And Proliferating Cells In The Mammary Gland
Stem Cells In The Normal Human Breast And Their Implications In Breast Cancer
The Menopausal Breast
128. Sexual Dysfunction in the Female
Normal Female Sexual Response
Endocrinology of Objective Arousal
Definitions and Diagnosis of Sexual Dysfunction
Pathophysiology of Female Sexual Dysfunction
Treatments For Sexual Dysfunction
Persistent Genital Arousal Disorder
Conclusion
129. Hormonal Control of Human Pregnancy and Parturition
Establishment of Pregnancy
Pregnancy Maintenance
Parturition and Birth Timing
Conclusion/Future Directions
130. Fetal and Neonatal Endocrinology
Overview
Placental Hormone Production and Transfer
Ectopic Fetal Hormone Production
Fetal Endocrine Systems
The Fetal Autonomic Nervous System
Fetal Pancreas and Glucose Homeostasis
Fetal Parathryoid and Bone Metabolism
Fetal Growth
Adaptations to Extrauterine Life
Future Directions
131. Hormonal Changes and Pregnancy Testing
Introduction
Pituitary Gland
Prolactin
Growth Hormone
Thyroid Gland
Adrenal Gland
Parathyroid Glands
Conclusion
Part 11. Multisystem Endocrine Disorders
132. Autoimmune Polyglandular Syndromes
Background
The Basis of Autoimmune Disease
Autoimmune Polyglandular Syndrome Type 1
Immumodysregulation Polyendocrinopathy Enteropathy X-Linked
Autoimmune Polyglandular Syndrome Type 2
Immune Checkpoint Inhibitor-Induced Polyendocrinopathy
133. Multiple Endocrine Neoplasia Type 1
Historical Aspects
Clinical Findings and Treatment
Molecular Genetics
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
134. Multiple Endocrine Neoplasia Types 2 and 3, and Medullary Thyroid Carcinoma
Prevalence and Epidemiology
Molecular Pathogenesis: Ret Protooncogene
Histology
Clinical Relevance of Germline Ret Variants in Multiple Endocrine Neoplasia Type 2 and Multiple Endocrine Neoplasia Type 3
Specific Genotype-Phenotype Correlations
Clinical Presentation
Screening in Multiple Endocrine Neoplasia Type 2 and Multiple Endocrine Neoplasia Type 3
Management Implications of Genetic Results
The Role of Somatic Mutations
Germline Screening
Natural Progression and Behavior of Multiple Endocrine Neoplasia Type 2 and Multiple Endocrine Neoplasia Type 3
Management Of Medullary Thyroid Carcinoma
Management of Pheochromocytoma
Management of Hyperparathyroidism
Conclusion
135. Neuroendocrine Tumor Syndromes
Introduction
Epidemiology
Etiology
Pathologic Classification and Prognosis
Diagnostic Approach and Clinical Presentation
Clinical Features of Functional net and Their Syndromes
Management Strategies for Functional Neuroendocrine Tumors
Conclusion
136. Ectopic Hormone Syndromes
History
Theoretical Considerations
Ectopic Adrenocorticotropic Hormone Syndrome
Ectopic Corticotropin-Releasing Hormone Secretion
Syndrome of Inappropriate Antidiuretic Hormone Secretion
Humoral Hypercalcemia of Malignancy
Oncogenic Osteomalacia
Ectopic Growth Hormone–Releasing Hormone
Non–Islet Cell Tumor Hypoglycemia
Other Pituitary Ectopic Hormones
Ectopic Gut Hormone Syndromes
Acknowledgments
137. Endocrine-Disrupting Chemicals and Human Health
The US Population is Less Healthy Today
Environmental Chemicals Contribute to Human Disease
Endocrine-Disrupting Chemicals are not Typical Poisons
Characteristics of Endocrine-Disrupting Chemicals
Health Effects of Environmental Chemicals
Mechanisms of EDC Actions
Dose-Response Characteristics of EDCS
Endocrine Systems: Disease Trends and Effects Of Edcs
Emerging Issues
Conclusion and Guidance for Clinicians
Index

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