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دانلود کتاب Williams Textbook of Endocrinology

دانلود کتاب کتاب غدد درون ریز ویلیامز

Williams Textbook of Endocrinology

مشخصات کتاب

Williams Textbook of Endocrinology

ویرایش: [14 ed.] 
نویسندگان: , , , ,   
سری:  
ISBN (شابک) : 0323555969, 9780323555968 
ناشر: Elsevier 
سال نشر: 2019 
تعداد صفحات: 1792
[2172] 
زبان: English 
فرمت فایل : PDF (درصورت درخواست کاربر به PDF، EPUB یا AZW3 تبدیل می شود) 
حجم فایل: 157 Mb 

قیمت کتاب (تومان) : 37,000



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توضیحاتی در مورد کتاب کتاب غدد درون ریز ویلیامز



به طور تخصصی پر کردن شکاف بین علوم پایه و اطلاعات بالینی، کتاب درسی غدد درون ریز ویلیامز، ویرایش چهاردهم، مجموعه ای برجسته از نویسندگان مشهور جهان را گرد هم می آورد تا بحث های معتبری را ارائه دهد. از طیف کامل اختلالات سیستم غدد درون ریز بزرگسالان و کودکان. فصل‌های جدید و بازنگری‌های مهم در سرتاسر شما را در جریان پیشرفت‌های اخیر در داروها، درمان‌ها، کارآزمایی‌های بالینی و موارد دیگر قرار می‌دهد. این مرجع ضروری یک منبع ضروری برای متخصصان غدد، جراحان غدد، متخصصین زنان، متخصصین داخلی، متخصصان اطفال و سایر پزشکانی است که نیاز به پوشش فعلی و جامع این حوزه چند وجهی دارند.

    . li> به روز با پیشرفت های اخیر در داروها، درمان ها و آزمایشات بالینی.
  • پوشش پیشرفته دیابت، سندرم متابولیک، اختلالات متابولیک استخوان، چاقی، بیماری تیروئید، اختلالات بیضه، جدیداً تعریف شده را ارائه می‌کند. اختلالات آدرنال و خیلی چیزهای دیگر - همه برای کمک به ارائه مراقبت مطلوب به هر بیمار طراحی شده اند.
  • شامل فصل های جدید در بار جهانی بیماری های غدد درون ریز، پیمایش است. دستورالعمل های غدد درون ریز و غدد درون ریز ترنسجندر.
  • شامل به روز رسانی های قابل توجهی در بخش دیابت، از جمله فصل جدیدی در فیزیولوژی ترشح انسولین و پوشش بیشتر دیابت نوع 2.
  • اطلاعات فعلی را در یک قالب بسیار مصور و کاربرپسند برای مرجع سریع ارائه می‌کند.
  • بهبود یافته li> نسخه کتاب الکترونیکی همراه با خرید. کتاب الکترونیکی پیشرفته شما به شما امکان می دهد به تمام متن، شکل ها و مراجع کتاب در دستگاه های مختلف دسترسی داشته باشید.

توضیحاتی درمورد کتاب به خارجی

Expertly bridging the gap between basic science and clinical information, Williams Textbook of Endocrinology, 14th Edition, brings together an outstanding collection of world-renowned authors to provide authoritative discussions of the full spectrum of adult and pediatric endocrine system disorders. New chapters and significant revisions throughout keep you up to date with recent advances in medications, therapies, clinical trials, and more. This essential reference is a must-have resource for endocrinologists, endocrine surgeons, gynecologists, internists, pediatricians, and other clinicians who need current, comprehensive coverage of this multifaceted field.

  • Up to date with recent advances in medications, therapies, and clinical trials.
  • Provides state-of-the-art coverage of diabetes, metabolic syndrome, metabolic bones disorders, obesity, thyroid disease, testicular disorders, newly defined adrenal disorders and much more - all designed to help you provide optimal care to every patient.
  • Contains new chapters on Global Burden of Endocrine Disease, Navigation of Endocrine Guidelines, and Transgender Endocrinology.
  • Includes significant updates to the Diabetes section, including a new chapter on Physiology of Insulin Secretion and greater coverage of Type 2 Diabetes.
  • Presents current information in a highly illustrated, user-friendly format for quick reference.
  • Enhanced
  • eBook version included with purchase. Your enhanced eBook allows you to access all of the text, figures, and references from the book on a variety of devices.


فهرست مطالب

Williams Textbook of Endocrinology
Copyright
Contributors
Preface
1 - Principles of Endocrinology
	The Evolutionary Perspective
	Endocrine Glands
	Transport of Hormones in Blood
	Target Cells as Active Participants
	Control of Hormone Secretion
	Hormone Measurement
	Endocrine Diseases
		Hormone Overproduction
		Hormone Underproduction
		Altered Tissue Responses to Hormones
		Tumors of Endocrine Glands
		Excessive Hormone Inactivation or Destruction
	Diagnostic and Therapeutic Uses of Hormones
	Future Perspectives
2 - Principles of Hormone Action
	Introduction to Hormone Signaling
	Ligands That Act Through Cell Surface Receptors
		Classic Peptide Hormones
		Nonpeptide Hormones That Act at Cell Surface Receptors
	Binding Properties of Cell Surface Receptors
	Cell Surface Hormone Receptors
		Ligand-Gated Ion Channels
		G Protein–Coupled Receptors
		Signaling by Heterotrimeric G Proteins
		Receptor Tyrosine Protein Kinases as Cell Surface Receptors
		Signaling by Receptor Tyrosine Protein Kinases
		Receptor Serine/Threonine Protein Kinases
		Signaling by Receptors That Associate With Enzymes
	Coupling of Cell Surface Receptors to Intracellular Signaling
		Downstream Signaling by Cyclic Adenosine Monophosphate
		Regulation by the Second Messengers Calcium and PKC
		Regulation of Protein Kinases by PI3K
		Regulation of Protein Kinases by Ras
	Disease Caused by Defective Cell Surface Receptors
		Insulin Resistance Syndromes
		Defects in Cell Surface Receptors That Control Growth
		Diseases Caused by Mutations in GPCRs and G Proteins
	Ligands That Act Through Nuclear Receptors
		General Features of Nuclear Receptor Ligands
		Subclasses of Nuclear Receptor Ligands
			Classic Hormones
			Vitamins
			Metabolic Intermediates and Products
			Endobiotics and Xenobiotics
		Orphan Receptors
		Variant Receptors
		Regulation of Ligand Levels
	Nuclear Receptor Signaling Mechanisms
		Domain Structure of Nuclear Receptors
		Nuclear Localization
		Hormone Binding
		Target Gene Recognition by Receptors
		Receptor Dimerization
	Receptor Regulation of Gene Transcription
		Ligand-Dependent Activation
		Repression of Gene Expression by Unliganded Receptor
		Ligand-Dependent Negative Regulation of Gene Expression: Transrepression
		Roles of Other Nuclear Receptor Domains
		Cross-Talk With Other Signaling Pathways
		Receptor Antagonists
		Tissue Selectivity of Ligands Interacting With Nuclear Receptors
	Nongenomic Actions of Nuclear Receptor Ligands
3 - Genetics of Endocrinology
	The Role of Genetics in Endocrinology
	Principles of Genetics
		A Brief Historical Perspective
		Heritability: An Estimate of the Importance of Genetic Factors to Disease Causation
		Human DNA Sequence Variation: Molecular Forms and Biologic Effects
		Factors Influencing the Biologic Impact of Genetic Variants in a Particular Gene
		Summary
	Genetics of Endocrine Diseases
		Mendelian Endocrine Diseases
			Genetic Architecture
			Disease Biology
			Clinical Translation
		Type 2 Diabetes
			Genetic Architecture
			Disease Biology
			Clinical Translation
		Short Stature
			Genetic Architecture
			Disease Biology
			Clinical Translation
		Lipids and Coronary Artery Disease
			Genetic Architecture
			Disease Biology
			Clinical Translation
		Considerations for Clinical Use of Genetic Information and Sequencing in Endocrinology
		Genome Screening in the General Population
		Genetic Information and Sequencing in Individual Patients
			Asymptomatic Individuals
			Symptomatic Individuals
		Avoiding Invasive Diagnostics
			Selection of Genetic Tests: Targeted Versus Genome-wide Approaches
			Limitations of Genomic Testing
		Interpretation of Identified Genetic Variants
		Using a Genetics Laboratory Report to Make Clinical Decisions
		Future Perspectives and Summary
4 - Laboratory Techniques for Recognition of Endocrine Disorders
	Laboratory Methods
		Antibody-Based Methods
			Classic Competitive Binding Immunoassays
				Antibody
				Labeled Antigen
				Unlabeled Antigen
				Separation of Reactants/Automation
				Quantitation
			Epitope-Specific Immunometric Assays
		Molecular Structure–Based Methods
			Extraction Methods
			Chromatographic Systems
			Mass Spectrometry
		Free Hormone Methods
		Nucleic Acid–Based Methods
			Hybridization Assays (Mutation Assays, Genotyping)
			Restriction Fragmentation
			Electrophoretic Separation
			Amplification
			Sequencing Methods
	Analytic Validation
		Intrinsic Performance Parameters
			Analytic Specificity
				Cross-Reactivity
				Interference
			Analytic Sensitivity
			Precision
			Accuracy
			Carryover
		Utilization Parameters
			Specimen Stability
			Reagent Stability
			Robustness (Assay Stability)
		Interpretation Parameters
			Reportable Range
			Reference Intervals
			Diagnostic Power
		Operational Parameters (Preanalytic Considerations)
			Specimen Types
				Whole Blood
				Serum
				Plasma
				Urine
				Saliva
				Fluids and Tissue From Fine-Needle Aspiration
	Quality Control
	Quality Assurance
	Classes of Assays
	Conclusion
	Acknowledgment
5 - The Global Burden of Endocrine Diseases
	Introduction
	Obesity and Excess Weight
		Prevalence and Trends
		The Burden of Excess Weight
	The Burden of Diabetes
		Prevalence, Incidence, and Mortality Trends
		Burden
	The Burden of Thyroid Diseases
	Perspectives for the Next Decade
6 - Navigating Through Clinical Practice Guidelines in Endocrinology
	Introduction
	Development of Trustworthy Clinical Practice Guidelines
		Identification of the Clinical Question
		Systematic Review of the Literature
		Evaluation of the Quality of the Evidence
		From Quality of the Evidence to Strength of Recommendation
	Clinical Practice Guidelines Recommendations
		Strong Recommendations
		Weak Recommendations (Also Called Conditional or Discretionary)
		Good Practice Statements
	Clinical Practice Guidelines in Endocrinology
	Using Clinical Practice Guidelines in Patient Care
		Case Study: Management of Gestational Diabetes Using Clinical Practice Guidelines in Patient Care
	Shortcomings of Clinical Practice Guidelines
	Guidelines as Tools That Support (Not Dictate) Care
	Disease-Specific and Context-Blind Guidelines
	Guideline Focus on Surrogate Outcomes (Not Patient-Important Outcomes)
	Quality and Trustworthiness of Clinical Practice Guidelines
	Conclusions
7 - Neuroendocrinology
	Historic Perspective
	Neural Control of Endocrine Secretion
		Neurosecretion
		Contribution of the Autonomic Nervous System to Endocrine Control
	Hypothalamic-Pituitary Unit
		Development and Differentiation of Hypothalamic Nuclei
		Anatomy of the Hypothalamic-Pituitary Unit
		The Median Eminence and Hypophysiotropic Neuronal System
	Circumventricular Organs
		Median Eminence
		Organum Vasculosum of the Lamina Terminalis and the Subfornical Organ
		Area Postrema
		Subcommissural Organ
	Pineal Gland
		The Pineal Is the Source of Melatonin
		Physiologic Roles of Melatonin
		Melatonin Receptors
		Melatonin Therapy in Humans
	Hypophysiotropic Hormones and Neuroendocrine Axes
		Feedback Concepts in Neuroendocrinology
		Endocrine Rhythms
		Thyrotropin-Releasing Hormone
			Chemistry and Evolution
			Effects on the Pituitary Gland and Mechanism of Action
			Extrapituitary Function
			Clinical Applications
			Regulation of Thyrotropin Release
			Feedback Control: Hypothalamic-Pituitary-Thyroid Axis
			Neural Control
			Circadian Rhythm
			Temperature
			Stress
			Suckling
			Starvation
			Dehydration-Induced Anorexia
			Infection and Inflammation
		Corticotropin-Releasing Hormone
			Chemistry and Evolution
			Effects on the Pituitary and Mechanism of Action
			Extrapituitary Functions
			Clinical Applications
			Feedback Control
			Neural Control
			Inflammation and Cytokines
			Other Factors Influencing Secretion of Corticotropin
				Circadian Rhythms
				Opiates
		Growth Hormone–Releasing Hormone
			Chemistry and Evolution
			Growth Hormone–Releasing Hormone Receptor
			Effects on the Pituitary and Mechanism of Action
			Extrapituitary Functions
			Growth Hormone–Releasing Peptides
			Clinical Applications
			Neuroendocrine Regulation of Growth Hormone Secretion
			Feedback Control
			Neural Control
			Other Factors Influencing Secretion of Growth Hormone
				Human Growth Hormone Rhythms
				External and Metabolic Signals
		Somatostatin
			Chemistry and Evolution
			Somatostatin Receptors
			Effects on Target Tissues and Mechanism of Action
			Clinical Applications of Somatostatin Analogues
		Prolactin-Regulating Factors
			Dopamine
			Prolactin-Releasing Factors
			Intrapituitary Regulation of Prolactin Secretion
			Neuroendocrine Regulation of Prolactin Secretion
			Feedback Control
			Neural Control
			Factors Influencing Secretion
				Circadian Rhythm
				External Stimuli
		Gonadotropin-Releasing Hormone and Control of the Reproductive Axis
			Chemistry and Evolution
			Anatomic Distribution
			Embryonic Development
			Action at the Pituitary
				Receptors
				Pulsatile Gonadotropin-Releasing Hormone Stimulation
			Regulatory Systems
			Feedback Regulation
			Regulation of the Ovarian Cycle
			Early Development and Puberty
			Reproductive Function and Stress
	Thermoregulation and Sleep-Wake Cycle
		Preoptic Area Is the Primary Hypothalamic Thermoregulatory Center
		Mechanisms for Thermoreception
		Central Circuitries Mediating Thermoregulation
		Modulators of Thermoregulatory Responses
			Thyroid Hormone
			Estrogen and Progesterone
			Neurokinin B
			Orexin-A
			Prostaglandins
			Opioids and Endocannabinoids
		Sleep-Wake Cycle
		Central Circuitries Mediating the Sleep-Wake Cycle
		Circadian Regulation of Sleep-Wake Cycle
		Somnogens
		Modifying Factors Influencing Sleep
	Neuroendocrine Disease
		Pituitary Isolation Syndrome
		Hypophysiotropic Hormone Deficiency
		Craniopharyngioma
		Hypophysiotropic Hormone Hypersecretion
		Neuroendocrine Disorders of Gonadotropin Regulation
			Precocious Puberty
				Idiopathic Sexual Precocity
				Neurogenic Precocious Puberty
				Hypothyroidism
				Tumors of the Pineal Gland
				Approach to the Patient with Precocious Puberty
				Management of Sexual Precocity
			Psychogenic Amenorrhea
			Neurogenic Hypogonadism in Males
		Neurogenic Disorders of Prolactin Regulation
		Neurogenic Disorders of Growth Hormone Secretion
			Hypothalamic Growth Failure
			Maternal Deprivation Syndrome and Psychosocial Dwarfism
			Neuroregulatory Growth Hormone Deficiency
			Neurogenic Hypersecretion of Growth Hormone
				Diencephalic Syndrome
				Growth Hormone Hypersecretion Associated With Metabolic Disturbances
				X-Linked Gigantism
		Neurogenic Disorders of Corticotropin Regulation
		Nonendocrine Manifestations of Hypothalamic Disease
		Paroxysmal Sympathetic Storms (Diencephalic Epilepsy)
		Narcolepsy
			Kleine-Levin Syndrome
			Hypothalamus and Neuropsychiatric Disorders
	Acknowledgments
8 - Pituitary Physiology and Diagnostic Evaluation
	Anatomy, Development, and Overview of Control of Hormone Secretion
		Anatomy
		Pituitary Blood Supply
		Pituitary Development
		Pituitary Transcription Factors
		Pituitary Stem Cells
		Pituitary Control
	Physiology and Disorders of Pituitary Hormone Axes
		Prolactin
			Physiology
				Lactotroph Cells
				Prolactin Structure
			Regulation
			Prolactin Secretion
			Prolactin Action
				Mammary Gland Development
				Lactation
				Reproductive Function
				Other Actions
				Prolactin Measurements
			Prolactin Deficiency
				Causes
				Manifestations
			Hyperprolactinemia
				Causes
					Physiologic Causes
						Macroprolactinemia. PRL is a 23-kDa single-chain polypeptide but may also circulate in high-molecular-weight forms. High-molecul...
					Pathologic Causes. Pathologic hyperprolactinemia may be caused by a prolactinoma, pituitary or sellar tumors that inhibit dopami...
					Drug-Induced Causes. A variety of medications cause minimal or moderate prolactin elevations. Neuroleptic drugs elevate PRL beca...
				Clinical Features
		Growth Hormone
			Somatotroph Cells
				Structure
			Regulation
				Ghrelin
			Extrapituitary GH
			Secretion
				GHRH and SRIF Interaction
				Interaction With Other Hormone Axes
			Action
				GHR Signaling
				Growth Hormone–Binding Proteins
				Metabolic Action
			Growth Hormone Assays
			Growth Hormone Deficiency
				Pathophysiology
				Presentation
				Evaluation
					Provocative Testing. The diagnosis of adult GHD is established by provocative testing of GH secretion (Table 8.7). Other hormone...
					Growth Hormone–Responsive Markers. These markers include IGF1, IGF binding protein 3 (IGFBP3), and the acid-labile subunit of th...
					Spontaneous GH Secretion. As pituitary GH secretion occurs episodically, accurate quantification of integrated GH secretion requ...
				Gene Expression Analysis
				Growth Hormone Replacement Therapy
					Growth Hormone Administration. GH secretion is greater in the young and greater in women than in men. It is recommended that the...
					Transition-Age Patients. GH treatment of the GH-deficient child normally is terminated when final height and epiphysis closure a...
					Precautions and Caveats of Treating With Human Growth Hormone. The most common side effects of hGH replacement include edema, ar...
				Investigational Uses of Growth Hormone
					Catabolic States. The anabolic actions of GH have prompted investigational use of GH in catabolic states, including surgery, tra...
					Osteoporosis. There is strong evidence that GH administered to otherwise healthy subjects with idiopathic osteoporosis improves ...
					Human Immunodeficiency Virus Infection. GH is Food and Drug Administration (FDA) approved for administration to adult patients w...
					Sports. The public policy issues of GH abuse in competitive sports have received much attention. GH has been widely abused by at...
					Aging. Disease mongering of declining GH status is rampant and spawned by unsubstantiated claims that GH is an antiaging hormone...
			GH Excess
		Adrenocorticotropic Hormone
			Physiology
				Corticotroph Cells
				Structure
			Regulation
				POMC Processing
				Extrapituitary and CNS Expression of POMC
			Melanocortin Receptors
			Adrenal Action
				Stress Response
				Circadian Periodicity
			Measurement of ACTH
			ACTH Deficiency
				Causes
				Clinical Features
				Evaluation
				Dynamic Testing for ACTH Deficiency
					Hypothalamic Testing. Insulin hypoglycemia is a potent endogenous stressor that evokes ACTH secretion as well as GH release. Ins...
					Pituitary Stimulation. Pituitary ACTH secretion is evoked by injecting either CRH or AVP. Ovine or human CRH (100 μg or 1 μg/kg)...
					Adrenal Stimulation. The acute response of the adrenal gland to a bolus ACTH injection reflects ambient ACTH concentrations to w...
				Adrenal Steroid Replacement
			ACTH Excess
				Causes
				Clinical Features
		Gonadotropins
			Physiology
				Gonadotroph Cells
				Gonadotropin Structure
			Regulation
				Gonadotropin-Releasing Hormone
				Inhibins and Activins
				Sex Steroids
			Secretion
			Action
				Female
				Male
			Gonadotropin Measurements
				α-Subunit Assays
				GnRH Stimulation Test
				Clomiphene Stimulation Test
			Gonadotropin Deficiency
				Causes
					Hypogonadotropic Hypogonadism. The genetic basis of HH was recognized over 60 years ago with the description by Kallmann of hypo...
					Kallmann Syndrome. Kallmann syndrome consists of defective GnRH neuronal development, with olfactory nerve agenesis or hypoplasi...
				Manifestations
				Management
					Evaluation. In evaluating hypogonadal patients in the absence of an obvious pituitary or gonadal disorder, the primary diagnosti...
					Sex Steroid Replacement Therapy. Estrogen or testosterone replacement is required for inducing and maintaining primary and secon...
					Fertility. In patients with HH, fertility may be achieved with gonadotropin or GnRH therapy. In males, even relatively low sperm...
		Thyroid-Stimulating Hormone
			Physiology
				Thyrotroph Cells
				Structure
			Regulation
			Secretion
				Regulatory Factors
			Action
			TSH Assays
			TSH Deficiency
				Causes
				Manifestations
				Treatment
			TSH Excess
	Developmental, Genetic, and Acquired Causes of Pituitary Failure
		Developmental Disorders
		Heritable Disorders
			HESX1, SOX2, SOX3, and OTX2
			LHX3 and LHX4
			PITX1 and PITX2
			PROP1
			POU1F1
			IGSF1
			TBX19
			NR5A1 and NR0B1
			Pituitary Stalk Interruption Syndrome
		Acquired Disorders
			Head Trauma
			Radiation
			Empty Sella Syndrome
			Clinical Features of Hypopituitarism
			Screening for Pituitary Failure
9 - Pituitary Masses and Tumors
	Pituitary Masses
		Pituitary Mass Effects
		Evaluation of Pituitary Masses
			Approach to the Patient Harboring a Pituitary Mass
			Imaging
				Receptor Imaging
			Neuro-Ophthalmologic Assessment of Pituitary Masses
				Visual Symptoms
			Clinical Signs and Approach
		Management of Pituitary Masses
			Surgical Management of Pituitary Tumors and Sellar Masses
				Goals of Surgery
				Indications for Transsphenoidal Surgery
				Side Effects
			Pituitary Radiation
				Principles
				Indications
				Side Effects
			Medical Management
	Parasellar Masses
		Types of Parasellar Masses
			Rathke Cysts
			Granular Cell Tumors
			Chordomas
			Craniopharyngiomas
			Meningiomas
			Gliomas
			Mucocele
			Parasellar Aneurysms
			Pituitary Infections
			Hematologic Malignancies
			Pituicytoma
			Sarcoidosis
			Langerhans Cell Histiocytosis
			Hereditary Iron Storage Diseases
			Idiopathic Retroperitoneal Fibrosis
			Metastases to the Pituitary Region
		Evaluation of Parasellar Lesions
		Primary Hypophysitis
			Lymphocytic Hypophysitis
				Clinical Features
				Laboratory Findings
				Treatment
			Granulomatous Hypophysitis
			Xanthomatous Hypophysitis
			Necrotizing Infundibulo-Hypophysitis
			IgG4-Related Hypophysitis
			Immune Checkpoint Inhibitor-Induced Hypophysitis
		Hemorrhage and Infarction
			Postpartum Pituitary Infarction
			Pituitary Apoplexy
				Clinical Features
				Management
		Pituitary Adenomas
			Pituitary Trophic Activity
				Benign Adenomas
				Hormonal Factors
				Genetic Factors
				Pituitary Senescence
		Familial Syndromes
			Multiple Endocrine Neoplasia Type 1
			Familial Isolated Pituitary Adenomas
			Carney Complex
			Pathogenesis
	Classification of Pituitary Tumors
		Aggressive Adenomas
			Malignant Pituitary Tumors
	Prolactin-Secreting Adenomas
		Pathology and Pathogenesis
		Clinical Features
			Hyperprolactinemia
			Tumor Mass Effects
		Evaluation
		Treatment
			Medical Treatment
				Bromocriptine
				Cabergoline
				Administration
				Adverse Effects of Dopamine Agonists
			Radiation Therapy
			Surgery
			Chemotherapy
			Pregnancy
	Nonfunctioning Pituitary Tumors
		Gonadotroph Cell Tumors
			Presentation
			Evaluation
			Treatment
				Surgery
				Postoperative Radiotherapy
				Expectant Observation for Incidentalomas
			Pregnancy
			Medications
		Silent Corticotroph Tumors
		Silent Subtype 3 Tumors
		Silent GH-Expressing Tumors
	Acromegaly
		Incidence
		Pathogenesis
			Pituitary Acromegaly
				Disordered GHRH Secretion or Action
				Disordered Somatotroph Cell Function
				McCune-Albright Syndrome
			Extrapituitary Acromegaly
				GHRH Hypersecretion
				Ectopic Pituitary Adenomas
				Peripheral Growth Hormone–Secreting Tumors
				Acromegaloidism
			Gigantism
			Clinical Features of Acromegaly
				Growth Hormone and Tumor Formation
			Endocrine Complications
			Morbidity and Mortality
		Diagnosis
			Measurement of Growth Hormone and IGF1 Levels
			Differential Diagnosis
		Treatment
			Aims
			Surgical Management
				Side Effects
			Radiation Therapy
				Side Effects
			Medical Management
				Dopamine Agonists
				SRLs
				Growth Hormone Receptor Antagonist
				SRLs and GH Receptor Antagonist Combination
			Management Approach
	ACTH-Secreting Tumors (Cushing Disease)
		Assessment of Surgical Outcome
		Medical Treatment
	Thyrotrophic Hormone-Secreting Tumors
		Pathology
		Presentation
		Evaluation
		Management
			Surgery
			Radiation Therapy
			SRLs
			Preoperative Management
		Silent TSH-Secreting Tumors
10 - Posterior Pituitary
	Anatomy
		Normal
		Ectopic Posterior Pituitary
	Synthesis and Release of Neurohypophyseal Hormones
	Physiology of Secretion of Vasopressin and Thirst
		Volume and Pressure Regulation
		Osmotic Regulation
		Thirst
		Clinical Consequences of Osmotic and Volume Regulation
		Reset Osmostat During Pregnancy
		Osmotic Regulation in Aging
	Diabetes Insipidus
		Causes of Diabetes Insipidus
			Diabetes Insipidus Due to Excess Fluid Intake (Primary Polydipsia)
			Hypothalamic/Central Diabetes Insipidus
			Diabetes Insipidus Due to Accelerated Metabolism of Vasopressin (Diabetes Insipidus of Pregnancy)
			Nephrogenic Diabetes Insipidus
		Approach to the Differential Diagnosis of Polyuric States
		Further Investigations of Diabetes Insipidus
		Treatment of Polyuric Conditions
			Central Diabetes Insipidus in Ambulatory Patients
			Central Diabetes Insipidus in Hospitalized Patients
			Central Diabetes Insipidus in Neurosurgical Patients
			Adipsic Diabetes Insipidus
		Treatment of Diabetes Insipidus in Pregnancy
		Treatment of Nephrogenic Diabetes Insipidus
			Treatment of Primary Polydipsia
		Diabetes Insipidus in Association With Other Therapeutic Decisions
			Routine Surgical Procedures
			Panhypopituitarism
			Hypertonic Encephalopathy
	The Syndrome of Inappropriate Antidiuresis
		Hypoosmolality and Hyponatremia
			Incidence
			Osmolality, Tonicity, and Serum [Na+]
		Pathogenesis of Hypoosmolality
			Solute Depletion
				Water Retention
			Adaptation to Hyponatremia: ICF and ECF Volume Regulation
			Differential Diagnosis of Hyponatremia and Hypoosmolality
				Decreased Extracellular Fluid Volume
				Increased Extracellular Fluid Volume
				Normal Extracellular Fluid Volume
		Syndrome of Inappropriate Antidiuresis
		Etiology
			Tumors
				Central Nervous System Disorders
				Drugs
				Pulmonary Disorders
				Other Causes
		Pathophysiology
			Sources of Vasopressin Secretion
				Pituitary Vasopressin Secretion—Inappropriate Versus Appropriate
				Patterns of Vasopressin Secretion
				Contribution of Natriuresis to the Hyponatremia of SIAD
				Cerebral Salt Wasting
				Renal Escape From Antidiuresis
		Hypoosmolar Symptoms, Morbidity, and Mortality
		Therapy of SIAD and Other Hypoosmolar Disorders
			General Principles
			Therapies for Treatment of Hyponatremia
				Hypertonic Saline
				Isotonic Saline
				Fluid Restriction
				Arginine Vasopressin Receptor Antagonists
				Urea
				Furosemide and NaCl
			Efficacy of Hyponatremia Treatment
			Hyponatremia Treatment Guidelines Based on Symptom Severity
			Monitoring the Serum [Na+] in Hyponatremic Patients
			Long-Term Treatment of Chronic Hyponatremia
	Oxytocin
		Lactation
		Parturition
		Behavior
11 - Thyroid Pathophysiology and Diagnostic Evaluation
	Phylogeny, Embryology, and Ontogeny
		Phylogeny
		Structural Embryology
		Functional Ontogeny
	Anatomy and Histology
	Iodine and the Synthesis and Secretion of Thyroid Hormones
		Dietary Iodine
		Iodide Metabolism by the Thyroid Cell
		Iodide Oxidation and Organification
		Iodothyronine Synthesis
		Storage and Release of Thyroid Hormone
			Deiodination of Iodotyrosines
		Role and Mechanism of Thyrotropin Effects
	Thyroid Hormones in Peripheral Tissues
		Plasma Transport
			Thyroxine-Binding Globulin
			Transthyretin
			Competition for T4 and T3 Binding to TBG and TTR by ­Therapeutic Agents
			Albumin
			Other Plasma Thyroid Hormone–Binding Proteins
		Free Thyroid Hormones
		T4 and T3 Transport Across Cell Membranes and Intracellular T3 Binding
		Iodothyronine Deiodination
			Enzymology and Regulation of the Selenodeiodinases
		Quantitative and Qualitative Aspects of Thyroid Hormone Metabolism
			Thyroid Hormone Turnover
			Sources of Intracellular T3
			Pharmacologic Agents Inhibiting Thyroid Hormone Deiodination
		Mechanism of Thyroid Hormone Action
	Regulation of Thyroid Function
		The Hypothalamic-Pituitary-Thyroid Axis
			Thyrotropin-Releasing Hormone Synthesis and Secretion
			Thyrotropin Synthesis and Secretion
		Iodine Deficiency
		Iodine Excess
			Effects of Increased Iodine Intake on Thyroid Hormone Synthesis
			Effects on Thyroid Hormone Release
		Thyroid Function in Pregnancy and in the Fetus and Newborn
			Fetal Thyroid Function
			Maternal-Fetal Interactions
			Thyroid Function in the Newborn
		Aging and the Thyroid
		Thyroid Function During Fasting or Illness
		The Thyroid Axis and Neuropsychiatric Illness
		Effects of Hormones on Thyroid Function
			Glucocorticoids
			Gonadal Steroids
			Growth Hormone
	Physical Evaluation of the Thyroid Gland
		Physical Examination
	Laboratory Assessment of Thyroid Status
		Tests of the Hypothalamic-Pituitary-Thyroid Axis
			Thyroid-Stimulating Hormone
			TSH in Patients with Thyroid Dysfunction
	Quantitation of Serum Thyroid Hormone Concentrations
		Total T4 and T3
		Concentrations of Free T4 and Free T3
		The Free T4 Index
		Causes of Abnormal TSH or Thyroid Hormone Concentrations
			Causes of a Suppressed TSH
			Causes of an Elevated TSH
		Tests That Assess the Metabolic Impact of Thyroid Hormones
			Basal Metabolic Rate
			Biochemical Markers of Altered Thyroid Status
		Serum Thyroglobulin
		Tests for Thyroid Autoantibodies
			Autoantibodies to Thyroid Peroxidase and Thyroglobulin
			Do Thyroglobulin and Thyroid Peroxidase Antibodies Have a Pathogenic Role?
			Thyroid Autoantibodies in Hashimoto Thyroiditis and Graves Disease
			Thyroid Autoantibodies in Nonautoimmune Thyroid Disorders
			Thyroid Autoantibodies in Pregnancy
			The Normal Population
		Radioiodine Uptake
			Physiologic Basis
			Radioactive Iodine Uptake
			The Perchlorate Discharge Test
			States Associated With Increased RAIU
				Hyperthyroidism
				Aberrant Hormone Synthesis
				Iodine Deficiency
				Response to Thyroid Hormone Depletion
				Excessive Hormone Losses
			States Associated With Decreased RAIU
				Exogenous Thyroid Hormone: Thyrotoxicosis Factitia
				Disorders of Hormone Storage
				Exposure to Excessive Iodine
12 - Hyperthyroid Disorders
	Clinical Manifestations of Thyrotoxicosis
		Cardiovascular System
		Protein, Carbohydrate, and Lipid Metabolism
		Sympathetic Nervous System and Catecholamines
		Nervous System
		Muscle
		Eyes
		Skin and Hair
		Respiratory System
		Alimentary System
		Skeletal System: Calcium and Phosphorus Metabolism
		Renal Function: Water and Electrolyte Metabolism
		Hematopoietic System
		Pituitary and Adrenocortical Function
		Reproductive Function
	Laboratory Diagnosis
	GRAVES DISEASE
	Graves Hyperthyroidism
		Clinical Presentation
		Pathology
		Immunopathogenesis
		TSH Receptor, the Major Autoantigen in Graves Disease
		Etiology
			Existential Factors
			Genetic Variants
			Environmental Insults
				Iodine
				Smoking
				Alcohol
				Selenium
				Stress
				Infections
				Drugs
		Diagnosis and Differential Diagnosis
		Natural History and Prognosis
			Treatment
			Antithyroid Drugs: Thionamides
				Mechanism of Action
				Adverse Effects (Table 12.4)
				Practical Use
				Other Drugs Used in Hyperthyroidism
				Radioactive Iodine
				Choice of Therapy
	Graves Orbitopathy
		Clinical Presentation
		Epidemiology
		Pathology
		Immunopathogenesis
		Genetics and Environment
		Natural History and Prognosis
		Diagnosis and Differential Diagnosis
			Ocular Symptoms and Signs
			Thyroid Autoimmunity
			Orbital Imaging
		Treatment
			General Measures
			Thyroid Treatment
			Eye Treatment
	Graves Dermopathy
	Pregnancy and the Thyroid
		Human Chorionic Gonadotropin
			Transient Gestational Thyrotoxicosis
			Abnormal Responses to Human Chorionic Gonadotropin
		Graves Disease During Pregnancy and the Postpartum Period
			Influence of Pregnancy on the Immune System
			Thyroid Antibodies in Pregnant Patients With Graves Disease
			Differential Diagnosis
			Diagnosis
			Treatment During Pregnancy
				Antithyroid Drugs in Pregnancy
				Danger of Antithyroid Drugs in Pregnancy
				Caring for the Pregnant Patient
				Iodide and Beta Blockers
				Surgery
				Consequences of Overtreatment
			Graves Disease in the Postpartum Period
				Changes in the Immune Response in the Postpartum Period
				Transient Postpartum Thyroiditis
				Presentation of Postpartum Graves Disease
				Preconception Counseling
				Nursing and Antithyroid Drugs
	Inherited Nonimmune Hyperthyroidism
	Toxic Multinodular Goiter
		Pathogenesis
		Clinical Presentation
		Laboratory Tests and Differential Diagnosis
		Treatment
			Radioiodine Therapy
			Surgery
			Additional Treatment Options
	Toxic Adenoma
		Pathogenesis
		Clinical Presentation
		Laboratory Tests
		Treatment
			Radioiodine Therapy
			Surgery
	Subclinical Hyperthyroidism
		Definition
		Diagnosis
		Treatment
	Induced Hyperthyroidism
	Amiodarone-Induced Thyrotoxicosis
		Epidemiology and Screening
		Diagnosis
		Management
		Prognosis
	Hyperthyroidism Due to Thyrotropin Secretion
		Pituitary Tumor
		Thyroid Hormone Resistance
	Tumor Chorionic Gonadotropin-Induced Hyperthyroidism
	Transient Thyrotoxicosis
		Overview
		Transient Thyrotoxicosis Due to Autoimmune (Hashimoto) Thyroiditis
			Transient Thyrotoxicosis From Painless Autoimmune Thyroiditis
			Transient Thyrotoxicosis from Painful Autoimmune Thyroiditis
		Clinical Presentation of Transient Autoimmune Thyrotoxicosis
		Diagnosis
		Natural History
		Treatment
		Subacute Thyroiditis
			Pathology
			Pathophysiology
			Clinical Picture
			Diagnosis
			Treatment
		Drug-Associated Thyroiditis
	Other Causes of Thyrotoxicosis With a Low Radioiodine Uptake
		Thyrotoxicosis Factitia
		Hamburger Thyrotoxicosis
		Thyrotoxicosis Due to Extrathyroidal Tissue
			Struma Ovarii
			Clinical Presentation
			Treatment
		Thyrotoxicosis Due to Metastatic Thyroid Carcinoma
13 - Hypothyroidism and Thyroiditis
	Hypothyroidism
		Clinical Presentation
			Skin and Appendages
			Cardiovascular System
			Respiratory System
			Alimentary System
			Central and Peripheral Nervous Systems
			Muscular System
			Skeletal System: Calcium and Phosphorus Metabolism
			Renal Function: Water and Electrolyte Metabolism
			Hematopoietic System
			Pituitary and Adrenocortical Function
			Reproductive Function
			Catecholamines
			Energy Metabolism: Protein, Carbohydrate, and Lipid Metabolism
			Current Clinical Picture
			Hypothyroidism in Infants and Children
		Laboratory Evaluation
			Primary and Central Hypothyroidism
			Differential Diagnosis
		Classification
			Immune-Mediated
				Autoimmune Hypothyroidism
				Risk Factors
				Iodine Deficiency (Endemic Goiter)
				Endemic Cretinism
				Iodide Excess
				Drugs Blocking Thyroid Hormone Synthesis or Release, Causing Goiter Formation
				Goitrogens in Foodstuffs or as Endemic Substances or Pollutants
				Cytokines
				Congenital Causes of Goiter
				Thyroid Infiltration Causing Hypothyroidism and Goiter
				Postablative Hypothyroidism
				Thyroid Agenesis or Dysplasia
				Thyroid Aplasia Due to Thyrotropin Receptor Unresponsiveness
				Transient Hypothyroidism
				Consumptive Hypothyroidism
				Defects in Conversion of Thyroxine to Triiodothyronine
				Hypothyroidism Due to Drug-Induced Thyroid Destruction
				Central Hypothyroidism
				Resistance to Thyroid Hormone
		Treatment
			Pharmacologic and Physiologic Considerations
			Institution of Replacement Therapy
				Infants and Children
				Monitoring Replacement Therapy
			Adverse Effects of Levothyroxine Therapy
			Patients With Hypothyroid Symptoms Despite Restitution of Normal Thyroid Function
		Special Aspects of Hypothyroidism
			Subclinical Hypothyroidism
			Metabolic Insufficiency
			Thyroid Function Testing in Patients Receiving Replacement Therapy for Unclear Reasons
			Emergent Surgery in the Hypothyroid Patient
		Heart Disease and Thyroid Hormone Therapy
			Coexisting Coronary Artery Disease and Hypothyroidism
			Thyroid Hormone for Compromised Cardiovascular Function
		Screening for Primary Hypothyroidism
		Myxedema Coma
	Thyroiditis
		Acute Infectious Thyroiditis
			Incidence
			Clinical Manifestations
		Riedel Thyroiditis
		Miscellaneous Causes
14 - Nontoxic Diffuse Goiter, Nodular Thyroid Disorders, and Thyroid Malignancies
	Structural and Functional Imaging of the Thyroid
		Ultrasonography
		External Scintiscanning
		Computed Tomography
		Magnetic Resonance Imaging
		Positron Emission Tomography (PET)
	Nontoxic Goiter and Thyroid Nodular Disease
		Definitions
		Epidemiology of Goiter
		Etiology and Pathophysiology of Diffuse Goiter
		Natural History of Goiter and Thyroid Nodules
		Clinical Presentation of Goiter and Nodules
		The Approach to Thyroid Nodular Disease
			The Evaluation of Patients With Nodular Disease
			Thyroid Nodule Fine-Needle Aspiration
		Management Options for Patients With Nontoxic Diffuse Goiter and Nodular Thyroid Disease
	Malignant Thyroid Disorders
		Classification and Staging of Thyroid Cancer
		Follicular Adenomas and Borderline Thyroid Lesions With Malignant Potential
		Papillary Thyroid Carcinoma
			Molecular Pathogenesis of Papillary Thyroid Carcinoma
			Presenting Features of Papillary Thyroid Carcinoma
			Risk of Papillary Thyroid Carcinoma Recurrence and Mortality
			Prediction of Papillary Thyroid Carcinoma Recurrence
		Follicular Thyroid Carcinoma
			Molecular Pathogenesis of Follicular Thyroid Carcinoma
			Hürthle Cell Carcinoma
			Presenting Features of Follicular Thyroid Carcinoma
			Risk of Follicular Thyroid Carcinoma Recurrence and Mortality
			Outcome Prediction for Follicular Thyroid Carcinoma
		Poorly Differentiated Carcinoma
		Undifferentiated (Anaplastic) Carcinoma
		Medullary Thyroid Carcinoma
			Histologic Diagnosis of Medullary Thyroid Carcinoma
			Clinical Presentation of Medullary Thyroid Carcinoma
			Prognosis for Medullary Thyroid Carcinoma
		Primary Malignant Lymphoma of the Thyroid
	The Surgical Treatment of Thyroid Malignancy
		Active Surveillance as an Alternative to Immediate Surgery in Low-Risk Differentiated Thyroid Cancer
		Selecting Total Thyroidectomy or Thyroid Lobectomy in Differentiated Thyroid Cancer: A Risk-Adapted Approach
		Determining the Extent of Initial Cervical Lymph Node Dissection in Differentiated Thyroid Cancer
		Surgical Approach to Medullary Thyroid Cancer
		Surgical Approach to Anaplastic Thyroid Cancer
	Postoperative Management of Thyroid Malignancy
		131I Administration
		External Radiotherapy
		TSH Suppressive Therapy
	Long-Term Follow-Up of Patients With Thyroid Cancer Following Initial Therapy
		Initial Follow-Up Recommendations for Differentiated Thyroid Cancer (First Year After Initial Therapy)
		Modifying Initial Follow-Up Recommendations for Differentiated Thyroid Cancer Using Response to Therapy Definitions
		Follow-Up Recommendations Based on Response to Therapy Status
		Risk-Adapted Follow-Up Recommendations for Medullary Thyroid Cancer
		Treatment of Thyroid Cancer Recurrence and Distant Disease
			Locoregional Recurrences of PTC and FTC
			Management of Distant Metastatic Disease
			Complications of Treatment With 131I
			Refractoriness to Radioactive Iodine
			Molecular Targeted Systemic Therapies
			Vandetanib
			Sorafenib
			Lenvatinib
			Therapy for Recurrence of Medullary Thyroid Carcinoma
				Vandetanib and Cabozantinib (XL184)
			Targeted Molecular Therapy
15 - The Adrenal Cortex
	The Adrenal Cortex—Historical Milestones
	Anatomy and Development
	Adrenal Steroids and Steroidogenesis
		Regulation of Adrenal Steroidogenesis: Functional Zonation of the Adrenal Cortex
		Glucocorticoid Secretion: The Hypothalamic-Pituitary-Adrenal Axis
			Pro-opiomelanocortin and ACTH
			Corticotropin-Releasing Hormone and Arginine Vasopressin
			The Stress Response and Immune-Endocrine Axis
			Circadian Rhythm
			Negative Feedback
			The ACTH Receptor and ACTH Effects on the Adrenal Gland
		Mineralocorticoid Secretion: The Renin-Angiotensin-Aldosterone Axis
		Adrenal Androgen Secretion
	Corticosteroid Hormone Action
		Receptors and Gene Transcription
		Corticosteroid-Binding Globulin and Corticosteroid Hormone Metabolism
		Effects of Glucocorticoids
			Carbohydrate, Protein, and Lipid Metabolism
			Skin, Muscle, and Connective Tissue
			Bone and Calcium Metabolism
			Salt and Water Homeostasis and Blood Pressure Control
			Anti-inflammatory Actions and the Immune System
			Central Nervous System and Mood
			Eye
			Gut
			Growth and Development
			Endocrine Effects
		Therapeutic Corticosteroids
			Administration
			Long-Term Therapy
		Adrenocortical Diseases
		Glucocorticoid Excess
			Cushing Syndrome
			Clinical Features of Cushing Syndrome
				Obesity and Weight Gain
				Reproductive Organs
				Psychiatric Features
				Bone
				Skin
				Muscle
				Cardiovascular Features
				Infections
				Metabolic and Endocrine Features
				Eye
	Classification and Pathophysiology of Cushing Syndrome
		ACTH-Dependent Causes
			Cushing Disease
			Ectopic ACTH Syndrome
			Ectopic Corticotropin-Releasing Hormone Syndrome
			Macronodular Adrenal Hyperplasia
		ACTH-Independent Causes
			Cortisol-Secreting Adrenal Adenoma and Carcinoma
			Primary Pigmented Nodular Adrenal Hyperplasia and Carney Syndrome
			McCune-Albright Syndrome
			Macronodular Hyperplasia
			Iatrogenic Cushing Syndrome
		Special Features of Cushing Syndrome
			Cyclic Cushing Syndrome
			Cushing Syndrome in Children
			Pregnancy
			Other Syndromes of Hypercortisolemia
			Alcohol
			Depression
			Obesity
		Investigation of Patients With Suspected Cushing Syndrome
			Question 1: Does This Patient Have Cushing Syndrome?
				Circadian Rhythm of Plasma Cortisol
				Salivary Cortisol
				Urinary Free Cortisol Excretion
				Low-Dose Overnight Dexamethasone Suppression Tests
				Other Causes of Hypercortisolemia: Pseudo-Cushing or True Cushing Syndrome?
				Diagnostic Guidelines
			Question 2: What Is the Cause of Cushing Syndrome in This Patient?
				Morning Plasma ACTH
				Plasma Potassium
				High-Dose Dexamethasone Suppression Test
				Corticotropin-Releasing Hormone Test
				Inferior Petrosal Sinus Sampling and Selective Venous Catheterization
			Imaging
				CT/MRI Scanning of Pituitary and Adrenal Glands
				Nuclear Medicine and Molecular Imaging Studies
		Treatment of Cushing Syndrome
			Adrenal Causes
			Pituitary-Dependent Cushing Syndrome
			Ectopic ACTH Syndrome
			Medical Treatment of Cushing Syndrome
		Prognosis of Cushing Syndrome
			Glucocorticoid Resistance
	Glucocorticoid Deficiency
		Primary and Central Hypoadrenalism
		Primary Hypoadrenalism
			Addison Disease
				Autoimmune Adrenalitis
				Infections
			Acquired Primary Adrenal Insufficiency
			Inherited Primary Adrenal Insufficiency
		Secondary Hypoadrenalism
			Inherited Central Hypoadrenalism
			ACTH Suppression by Exogenous Glucocorticoids
			Hypoadrenalism During Critical Illness
		Clinical Features of Adrenal Insufficiency
		Investigation of Hypoadrenalism
			Routine Biochemical Profile
			Mineralocorticoid Status
			Assessing Adequacy of Function of the HPA Axis
				Testing the HPA Axis During Critical Illness
				Other Tests
		Treatment of Acute Adrenal Insufficiency
		Long-Term Replacement Therapy
	Congenital Adrenal Hyperplasia
		21-Hydroxylase Deficiency
			Simple Virilizing Form
			Salt-Wasting Form
			Nonclassic or Late-Onset 21-Hydroxylase Deficiency
			Heterozygote 21-Hydroxylase Deficiency
			Molecular Genetics
			Diagnostic Criteria
			Treatment
			Long-Term Complications and Comorbid Conditions
		11β-Hydroxylase Deficiency
		17α-Hydroxylase Deficiency
		P450 Oxidoreductase Deficiency: Apparent Combined 17α-Hydroxylase and 21-Hydroxylase Deficiencies
		3β-Hydroxysteroid Dehydrogenase Deficiency
		StAR Deficiency: Congenital Lipoid Adrenal Hyperplasia
		P450 Side-Chain Cleavage Deficiency
		Cortisone Reductase Deficiency
		Mineralocorticoid Deficiency
			Primary Defects in Aldosterone Biosynthesis: Aldosterone Synthase Deficiency
			Postadrenalectomy Hypoaldosteronism
			Defects in Aldosterone Action: Pseudohypoaldosteronism
			Hyporeninemic Hypoaldosteronism
	Adrenal Adenomas, Incidentalomas, and Carcinomas
		Adenomas
		Incidentalomas
		Carcinomas
		Etiology of Adrenal Tumors
	Acknowledgments
16 - Endocrine Hypertension
	Adrenal Medulla and Catecholamines
		Catecholamine Synthesis
		Catecholamine Storage and Secretion
		Catecholamine Metabolism and Inactivation
	Pheochromocytoma and Paraganglioma
		History
		Clinical Presentation
		Syndromic Forms of Pheochromocytoma and Paraganglioma
			Multiple Endocrine Neoplasia Type 2A
			Multiple Endocrine Neoplasia Type 2B
			von Hippel-Lindau Disease
			Neurofibromatosis Type 1
			Congenital Polycythemia
			Carney Triad
		Congenital Heart Disease
		Other Genetic Forms of Pheochromocytoma and Paraganglioma
			Succinate Dehydrogenase Gene Mutations
			TMEM127 Mutations
			MAX Mutations
			FH Mutations
		Genetic Testing
		Evaluation and Monitoring of Carriers of Succinate Dehydrogenase Mutations
		Diagnostic Investigation
			Differential Diagnosis
			Case Detection
				Measurement of Fractionated Metanephrines and Catecholamines in Urine and Plasma
				Other Tests That Have Been Used to Assess for Pheochromocytoma
				Renal Failure
				Factitious Pheochromocytoma
			Localization
				Imaging Phenotype
				68Ga-DOTATATE PET/CT and 123I-MIBG Scintigraphy
				Other Localizing Procedures
		Treatment
			Preoperative Management
				α-Adrenergic Blockade
				β-Adrenergic Blockade
				Catecholamine Synthesis Inhibitor
				Calcium Channel Blockers
			Acute Hypertensive Crises
			Anesthesia and Surgery
			Long-Term Postoperative Follow-Up
		Metastatic Pheochromocytoma and Paraganglioma
		Pheochromocytoma in Pregnancy
	Renin-Angiotensin-Aldosterone System
		Renin and Angiotensin
		Aldosterone
	Primary Aldosteronism
		History
		Prevalence
		Clinical Presentation
		Diagnosis
			Case-Detection Tests
			Confirmatory Tests
				Oral Sodium Loading Test
				Intravenous Saline Infusion Test
				Fludrocortisone Suppression Test
			Subtype Studies
				Computed Tomography of the Adrenal Glands
				Adrenal Venous Sampling
				Noninvasive Alternatives to Adrenal Vein Sampling
			Familial Hyperaldosteronism
				Glucocorticoid-Remediable Aldosteronism: Familial Hyperaldosteronism Type I—CYP11B1/CYP11B2 Germline Chimeric Gene
				Familial Hyperaldosteronism Type II—CLCN2 Chloride Channel Germline Mutations
				Familial Hyperaldosteronism Type III—Germline KCNJ5 Mutations
				Familial Hyperaldosteronism Type IV—Germline CACNA1H Gene Mutations
				Primary Aldosteronism With Seizures and Neurologic Abnormalities (PASNA)—Germline CACNA1D Mutations
				Primary Aldosteronism and ARMC5 Mutations
				Somatic Mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 Genes
			Aldosterone-Producing Cell Clusters
			Cortisol Cosecretion
		Principles of Treatment
			Surgical Treatment of Aldosterone-Producing Adenoma and Unilateral Hyperplasia
			Pharmacologic Treatment
		Primary Aldosteronism in the Setting of Pregnancy
	Other Forms of Mineralocorticoid Excess or Effect
		Hyperdeoxycorticosteronism
			Congenital Adrenal Hyperplasia
				11β-Hydroxylase Deficiency
				17α-Hydroxylase Deficiency
			Deoxycorticosterone-Producing Tumor
			Primary Cortisol Resistance
		Apparent Mineralocorticoid Excess Syndrome
		Liddle Syndrome: Abnormal Renal Tubular Ionic Transport
	Other Endocrine Disorders Associated With Hypertension
		Cushing Syndrome
		Thyroid Dysfunction
			Hyperthyroidism
			Hypothyroidism
		Renin-Secreting Tumor
		Acromegaly
17 - Physiology and Pathology of the Female Reproductive Axis
	Reproductive Physiology
	Reproductive Functions of the Hypothalamus
		Gonadotropin-Releasing Hormone
		Regulation of Gonadotropin-Releasing Hormone Secretion
		Gonadotropin-Releasing Hormone Analogues
			Peptide Gonadotropin-Releasing Hormone Agonists
			Peptide Gonadotropin-Releasing Hormone Antagonists
			Nonpeptide Gonadotropin-Releasing Hormone Antagonists
	Reproductive Functions of the Anterior Pituitary
		Gonadotrophs
		Gonadotropin-Releasing Hormone Receptor
		Luteinizing Hormone and Follicle-Stimulating Hormone
		Regulation of Circulating Levels of Follicle-Stimulating Hormone and Luteinizing Hormone
	Ovary
		Genetic Determinants of Ovarian Differentiation and Folliculogenesis
		Oocytes
		Granulosa Cell Layer
		Theca Cell Layer
		Follicles
		Ovulation
			Corpus Luteum
			Ovarian Follicle-Stimulating Hormone and Luteinizing Hormone Receptors
				Role of Follicle-Stimulating Hormone in Ovarian Function
				Role of Luteinizing Hormone in Ovarian Function
		Ovarian Steroidogenesis
			Steroidogenic Genes and Their Functions in the Ovary
				C21 Steroids
				C19 Steroids
				C18 Steroids
			Two-Cell Theory for Ovarian Steroidogenesis
			Peptide Hormones Produced by the Ovary
		Overview of the Hormonal Changes During the Ovarian Cycle
		Extraovarian Steroidogenesis
	Endometrium
		Functional Anatomy of the Endometrium
		Hormone-Induced Morphologic Changes of the Endometrium
		Effects of Ovarian Steroids on Endometrium
			Estrogen Action
			Progesterone Action
		The Receptive Phase of the Endometrium for Implantation
		Control of Endometrial Function With the Use of Exogenous Hormones
		Mechanism of Menstruation
	Approach to the Woman With Reproductive Dysfunction
		History
		Physical Examination
	Disorders of the Female Reproductive System
		Chronic Anovulation
		Hypothalamic Anovulation
			Functional Hypothalamic Amenorrhea
				Diagnosis of Functional Hypothalamic Amenorrhea
				Pathophysiology of Functional Hypothalamic Anovulation
				Hypothalamic Anovulation and Exercise
				Hypothalamic Anovulation Associated With Eating Disorders
				Treatment and Management of Functional Hypothalamic Anovulation
		Chronic Anovulation Associated With Pituitary Disorders
		Chronic Anovulation Associated With Androgen Excess
			Approach to the Patient With Androgen Excess
			Origins of Androgens
			Laboratory Evaluation of Androgen Action
			Causes of Androgen Excess
			Idiopathic Hirsutism
			Androgen-Secreting Tumors of the Ovary and Adrenal
			Nonneoplastic Adrenal Disorders and Androgen Excess
			Laboratory Testing to Aid the Differential Diagnosis of Androgen Excess
			Treatment of Hirsutism
				Oral Contraceptives
				Spironolactone
				Cyproterone Acetate
				Finasteride
				Flutamide
				Metformin and Thiazolidinediones
				Lifestyle Modification
				A Comprehensive Treatment Strategy for Hirsutism
		Polycystic Ovary Syndrome
			Historical Perspective
			Diagnosis of Polycystic Ovary Syndrome and Laboratory Testing
			Gonadotropin Production in Polycystic Ovary Syndrome
			Steroid Production in Polycystic Ovary Syndrome
			Production of Sex Hormone–Binding Globulin in Polycystic Ovary Syndrome
			Follicular Fate in Polycystic Ovary Syndrome
			Ovarian Hyperthecosis
			Genetics of Polycystic Ovary Syndrome
			Insulin Resistance and Polycystic Ovary Syndrome
				Role of Obesity in Insulin Resistance and Anovulation
				Laboratory Evaluation of Metabolic Syndrome in PCOS
				Use of Antidiabetic Drugs to Treat Anovulation and Androgen Excess
			Management of Long-Term Deleterious Effects of Polycystic Ovary Syndrome
			Ovulation Induction in Polycystic Ovary Syndrome
				Clomiphene Citrate
				Aromatase Inhibitors
				Metformin
				Low-Dose Gonadotropin Therapy
		Premature Ovarian Insufficiency
			Diagnosis and Management of Premature Ovarian Insufficiency
	Diagnosis and Management of Anovulatory Uterine Bleeding
		Characteristics of Normal Menses
		Terminology Describing Abnormal Uterine Bleeding
		Uterine Bleeding in Response to Steroid Hormones
			Estrogen Withdrawal Bleeding
			Estrogen Breakthrough Bleeding
			Progesterone Withdrawal Bleeding
			Progestin Breakthrough Bleeding
		Causes of Irregular Uterine Bleeding
		Management of Anovulatory Uterine Bleeding
			Oral Contraceptives
				Oral Contraceptives and Acute Excessive Uterine Bleeding Associated With Anemia
				Oral Contraceptives and Chronic Irregular Uterine Bleeding
			Synthetic Progestins
			High-Dose Estrogen for Acute Excessive Uterine Bleeding
			Gonadotropin-Releasing Hormone Analogues for Excessive Anovulatory Uterine Bleeding
	Hormone-Dependent Benign Gynecologic Disorders
		Endometriosis
			Pathology
			Mechanism of Disease
			Diagnosis
			Treatment
		Uterine Leiomyomas
	Management of Menopause
		Consequences of Menopause
			Perimenopause Stage
			Menopause Features
			Biosynthesis of Estrogen and Other Steroids in the Postmenopausal Woman
		Postmenopausal Uterine Bleeding
		Hot Flashes
		Urogenital Atrophy
		Postmenopausal Osteoporosis
	Postmenopausal Hormone Therapy
		The Long-Term Benefits and Side Effects of Hormone Therapy
		Risks and Contraindications of Hormone Therapy
			Coronary Heart Disease
			Stroke
			Pulmonary Embolism
			Breast Cancer
			Dementia
			Hypertriglyceridemia
			Gallbladder Disease
			Urinary Incontinence
		Indications for Hormone Therapy
			Hot Flashes
			Fractures
			Diabetes
		Post-WHI Recommendations for Hormone Therapy
		Target Groups for Hormone Therapy
		Estrogen Preparations and Beneficial Dose of Estrogen
			Oral Estrogens: Combined Conjugated Equine Estrogens
			Transdermal Estrogen
			Vaginal Estrogen
		Management of Breakthrough Bleeding During Postmenopausal Hormone Therapy
		Management of Menopausal Symptoms in Breast Cancer Survivors
		Selective Estrogen Receptor Modulators and Bisphosphonates for Osteoporosis Prevention
			Tibolone for Osteoporosis Prevention
18 - Hormonal Contraception
	Choosing a Contraceptive Method
	Combined Estrogen and Progestin Contraceptives
		The Combined Oral Contraceptive Pill
			Composition and Formulations
			Mechanism of Action, Efficacy, Administration, and Effect on Pregnancy
			Noncontraceptive Health Benefits
			Side Effects
			Health Risks
				Thromboembolic Disease
				Myocardial Infarction and Thrombotic Stroke
				Breast Cancer
				Cervical Cancer
			Use of Concomitant Medications With Combined Oral Contraceptives Pills
		Contraceptive Vaginal Ring and Transdermal Patch
			Transdermal Contraceptive Patch
			Contraceptive Vaginal Ring
	Progestin-Only Contraceptive Methods
		Progestin-Only Oral Contraceptive Pill
			Mechanism of Action
			Efficacy
			Starting the Progestin-Only Pill
			Side Effects of Progestin-Only Oral Contraceptives
			Other Effects
			Progestin-Only Oral Contraceptives During Lactation
		Depot Medroxyprogesterone Acetate for Contraception
			Formulations and Pharmacology
			Administration of DMPA
				Starting Injections
				Repeat Injections
			Side Effects of DMPA
			Risks and Benefits of DMPA
				Effect on Cancer Risk
				Effect on Cardiovascular Risk
				Effect on Skeletal Health
				Effect on Sexually Transmitted Infections
				Effect on Return of Fertility
		Progestin-Releasing Intrauterine Devices
			Contraceptive Uses
			Expanding the Use of IUDs
			Abnormal Bleeding, Expulsion, and Uterine Perforation
			Upper Genital Tract Infection and Infertility
			Metabolic and Systemic Effects
			Noncontraceptive Uses of the Levonorgestrel-Releasing Intrauterine System
				Heavy Menstrual Bleeding
				Symptomatic Fibroids and Uterine Adenomyosis
				Endometriosis
				Endometrial Protection With Estrogen Replacement Therapy
				Endometrial Protection With Tamoxifen Use
				Treatment for Endometrial Hyperplasia or Carcinoma
		Contraceptive Implants
			Description and Pharmacology
			Mechanism of Action and Efficacy
			Safety and Side Effect Profile
			Patient Selection
			Insertion and Removal
	Emergency Contraception
		Emergency Contraception Regimens
		Mechanism of Action
		Efficacy
		Indications
		Side Effects
			Ongoing Contraception
	Clinical Challenges in Contraceptive Care
		Hormonal Contraception for Adolescents
			Combined Hormonal Contraceptives in Adolescents
			Injectable Contraceptives in Adolescents
		Hormonal Contraception in Postpartum and Lactating Women
		Hormonal Contraception in Women Older Than 35 Years
		Discontinuation of Hormonal Contraception at Menopause
		Contraception in Women With Underlying Medical Conditions
		Hormonal Contraception in Obese Women
		Hormonal Contraception in Women Taking Antiepileptic Drugs
		Hormonal Contraception in Women Taking Antibiotics
		Hormonal Contraception in HIV-Positive Women
		Hormonal Contraception and Chronic Hypertension
		Hormonal Contraception in Women With Diabetes
		Hormonal Contraception in Women Awaiting Surgery
		Hormonal Contraception in Women With a History of Thromboembolism
		Hormonal Contraception in Women Taking Anticoagulation Therapy
		Hormonal Contraception for Women With Migraine Headaches
		Hormonal Contraception in Women With Systemic Lupus Erythematosus
		Hormonal Contraception in Women With Sickle Cell Disease
		Hormonal Contraception in Depression
19 - Testicular Disorders
	Functional Anatomy and Histology
		The Testis
		Seminiferous Tubule
		Spermatogenesis
			Proliferative Phase
			Meiotic Phase
			Spermiogenesis
			Germ Cell Loss
			Organization of Spermatogenesis
		Sperm Transport and Fertilization
		Spermatozoa
		Interstitium
	Testis Development
		Fetal Development
		Testis Descent
		Postnatal Development
		Pubertal Development
	Adult Physiology
		Hypothalamic-Pituitary-Testicular Axis
		Central Nervous System Regulation of Gonadotropin-Releasing Hormone Secretion
		GnRH Regulation of Gonadotropin Secretion
		Gonadotropin Control of Testicular Function
			LH Regulation of Leydig Cells
			Leydig Cell Production of Testosterone and INSL3
			FSH and Testosterone Regulation of Sertoli Cells
				Maintenance of Seminiferous Tubule Structure and Compartmentalization
				Provision of Nutrients and Growth Factors to Developing Germ Cells and Spermatozoa
				Translocation, Sculpting, and Release of Developing Germ Cells
				Secretion of Seminiferous Tubule Fluid
				Production of Reproductive Hormones
			Paracrine and Autocrine Regulation of Testis Function
			Hormonal Control of Spermatogenesis
				Initiation of Spermatogenesis
				Maintenance of Spermatogenesis
		Negative Feedback Regulation of Gonadotropin Secretion
		Testosterone Transport, Metabolism, and Actions
			Circulating Testosterone
			Active Metabolism and Catabolism of Testosterone
				Aromatization of Testosterone to Estradiol
				5α-Reduction of Testosterone to DHT
				Catabolism of Testosterone
		Mechanisms of Androgen Action
		Androgen Effects at Various Stages of Sexual Development
	Male Hypogonadism
		Clinical Manifestations
			Fetal Androgen Deficiency
			Prepubertal Onset of Androgen Deficiency
			Adult Androgen Deficiency
			Isolated Impairment of Sperm Production or Function
		History and Physical Examination
		Differential Diagnosis
			Sexual Dysfunction
				Hypoactive Sexual Desire Disorder and Erectile Dysfunction
				Ejaculatory Disorders and Orgasmic Dysfunction
			Gynecomastia
				Causes of Gynecomastia
				Evaluation
				Treatment
			Infertility
				Causes of Male Infertility
				Evaluation
				Treatment
		Diagnosis of Male Hypogonadism
			Clinical Manifestations of Androgen Deficiency
			Testosterone Measurements
				Variability in Testosterone Concentrations
				Total Testosterone Assays
				Total Testosterone Affected by Alterations in SHBG
				Transient Suppression of Testosterone
			Screening and Case Finding for Androgen Deficiency
			Seminal Fluid Analysis
			Gonadotropin Measurements
				Androgen Deficiency and Impaired Sperm Production
				Isolated Impairment of Sperm Production or Function
			Further Evaluation
		Causes of Primary Hypogonadism
			Androgen Deficiency and Impairment in Sperm Production
				Congenital or Developmental Disorders
				Acquired Disorders
				Systemic Disorders
			Isolated Impairment of Sperm Production or Function
				Congenital or Developmental Disorders
				Varicocele
				Acquired Disorders
				Systemic Disorders
		Causes of Secondary Hypogonadism
			Androgen Deficiency and Impairment in Sperm Production
				Congenital or Developmental Disorders
				Acquired Disorders
				Systemic Disorders
			Isolated Impairment of Sperm Production or Function
				Congenital or Developmental Disorders
				Acquired Disorders
		Androgen Resistance Syndromes
			Congenital Disorders
			Acquired Disorders
		Treatment of Androgen Deficiency
			Functional Versus Organic Causes of Hypogonadism
			Testosterone Replacement Therapy
				Therapeutic Goals and Management
				Testosterone Formulations
				Testosterone Formulations Available Outside the United States
				Nontestosterone Therapies for Male Hypogonadism
				Monitoring Clinical Response and Testosterone Concentrations
				Risks and Adverse Effects
			Gonadotropin Therapy
20 - Sexual Dysfunction in Men and Women
	Human Sexual Response Cycle
	Physiologic Mechanisms of Human Sexual Response
		Physiology of Desire and Arousal
			Functional Brain Imaging of Sexual Arousal in Men and Women
				Neurotransmitters and Hormones Involved in Sexual Desire and Subjective Arousal
			Animal Models
			Genital Sexual Congestion and Arousal
		Physiologic Mechanisms of Penile Erection
			Penile Anatomy and Blood Flow
			Penile Innveration
			Hemodynamic Changes During Penile Erection
			Biochemical Regulation of Cavernosal Smooth Muscle Tone
				Potassium Channels
				Connexin43 Gap Junctions
				Nitric Oxide
				Cyclic Nucleotide Phosphodiesterases
				Regulation of Sensitivity to Intracellular Calcium by Rho A/Rho Kinase Signaling
		Mechanisms of Ejaculation
	Role of Testosterone in Regulating Sexual Function in Men
	Physiology of Physical Sexual Arousal in Women: Genital Congestion
	Physiology of Orgasm
	Revised Definitions of Sexual Dysfunction in Men
		Male Hypoactive Sexual Desire Disorder
		Erectile Dysfunction
			Prevalence and Incidence
			Risk Factors for Erectile Dysfunction
			Erectile Dysfunction as a Marker of Cardiovascular Disease
			Lower Urinary Tract Symptoms and ED
		Ejaculatory Disorders
		Delayed Ejaculation
		Retrograde Ejaculation
	Current Definitions of Sexual Disorders in Women
		Sexual Interest/Arousal Disorder
		Female Orgasmic Disorder
		Genitopelvic Pain/Penetration Disorder
		Persistent Genital Arousal Disorder
	Sexual Dysfunction in the Context of Endocrine Disease
		Endocrine Disorders and Sexual Dysfunction in Men
			Androgen Deficiency Syndromes
			Diabetes and Sexual Dysfunction in Men
			Sexual Dysfunction Associated With Therapies for Benign Prostatic Hypertrophy
			Hyperprolactinemia and Sexual Dysfunction
			Sexual Dysfunction in Patients With Thyroid Disease
			Sexual Dysfunction in Men With Metabolic Syndrome
		Endocrine Disorders and Sexual Dysfunction in Women
			Thyroid Disease in Women
			Hyperprolactinemia in Women
			Diabetes in Women
			Metabolic Syndrome in Women
			Polycystic Ovary Syndrome
			Congenital Adrenal Hyperplasia
			Pituitary Disease in Women
			Adrenal Insufficiency in Women
			Natural Menopause
			Surgical Menopause
			Aging-Associated Decline in Sex Hormone Precursors in Women
			Selective Estrogen Receptor Modulators
			Hormonal Contraceptives
			Androgen Insensitivity Syndrome
	Assessment of Sexual Dysfunction
		Evaluation of Men With Sexual Dysfunction
		Evaluation of Women With Sexual Dysfunction
			Physical Examination
			Laboratory Testing
	Management of Sexual Dysfunction in Men
		Treatment of Hypoactive Sexual Desire in Men
		Treatment of Erectile Dysfunction
			First-Line Therapies
				Psychosexual Counseling
				Selective Phosphodiesterase 5 Inhibitors
			Second-Line Therapies
				Vacuum Devices for Inducing Erection
				Intraurethral Therapies
				Intracavernosal Injection of Vasoactive Agents
			Third-Line Therapies
				Penile Prosthesis
				Testosterone Replacement in Androgen-Deficient Men Presenting With Erectile Dysfunction
				Therapies With Either Unproven Efficacy or Limited Efficacy Data
				Gene Therapy and Erectile Dysfunction
				Potential of Stem Cell Therapy for Erectile Dysfunction
		Management of Retrograde Ejaculation
	Management of Sexual Dysfunction in Women
		Management of Low Desire and Arousal in Women
			Psychoeducation
			Cognitive Behavioral Therapy
			Mindfulness-Based Cognitive Therapy
			Sex Therapy
			Outcome of Psychological Treatments for Women’s Sexual Dysfunctions
		Management of Women’s Orgasmic Disorder
		Management of Genitopelvic Pain/Penetration Disorder (Dyspareunia and Vaginismus)
			Management of Provoked Vestibulodynia
			Management of Phobic Reflex Pelvic Muscle Contractions Component of Genitopelvic Pain/Penetration Disorder (Vaginismus)
		Testosterone Therapy for Women With Sexual Dysfunction
			Testosterone Plus a Phosphodiesterase Inhibitor
			Limitations of Trials of Testosterone Therapy in Women
			Risks of Testosterone Therapy
			Needed Research in the Area of Testosterone Supplementation
		Oral Dehydroepiandrosterone for Sexual Dysfunction in Healthy Women
		Local Dehydroepiandrosterone Therapy for Sexual Dysfunction in Healthy Women
		Estrogen Therapy for Women With Sexual Dysfunction
			Vaginal Lubricants and Moisturizers
			Systemic Estrogen
		Approved But Not Recommended Medication for the Former DSM-IV Hypoac­tive Sexual Desire Disorder
21 - Transgender Endocrinology
	Introduction
		Definitions and Diagnosis of Gender Dysphoria
		Prevalence of Gender Nonconforming Identity
		Biological Determinants of Gender Identity
	Care of Transgender Youth
		Outcomes of Current Treatment Models for Transgender Youth and Potential Adverse Effects
			Mental Health Outcomes
			Potential Adverse Effects of Pubertal Blockers in Transgender Youth
				Skeletal Health
				Fertility
				Brain
				Body Mass Index and Body Composition
			Potential Adverse Effects of Gender-Affirming Sex Hormones in Transgender Adolescents
	Care of Transgender Adults
		Transfeminine Hormone Therapy
			Estrogen
			Testosterone-Lowering Agents
			5α-Reductase Inhibitors
			Progesterone
		Transmasculine Hormone Therapy
		Potential Adverse Effects of Gender-Affirming Sex Hormones in Transgender Adults
		Potential Risks Associated With Transfeminine Hormone Therapy
			Venous Thrombosis and Pulmonary Embolism
			Myocardial Infarction and Cerebrovascular Accidents
			Hypertriglyceridemia
			Hyperprolactinemia
			Osteoporosis
			Breast Cancer
			Liver Dysfunction
		Potential Risks Associated With Transmasculine Hormone Therapy
			Erythrocytosis
			Hyperlipidemia
			Uterine and Cervical Cancer
	Barriers to Care and Priorities for Research for Transgender Youth and Adults
	References
22 - Endocrine Changes in Pregnancy
	Placental Development
		Sex Differences in the Placenta
	Maternal Adaptations to Pregnancy
		Physiologic Adaptations
		Metabolic Adaptations
	Maternal Endocrine Alterations
		Pituitary Gland
		Thyroid Gland
			Parathyroid Glands
		Pancreas
		Adrenal Glands
		Renin-Angiotensin System
	Placental Hormone Production
		Sex Steroid Production From the Maternal-Fetal-Placental Unit
		Protein Hormones
			Human Chorionic Gonadotropin
				Chemistry
				Biosynthesis
				Metabolism
				Physiologic Functions
				Gestational Trophoblastic Disease
			Human Placental Lactogen
			Placental Growth Hormone
			Human Chorionic Corticotropin
			Hypothalamic Peptides
				Gonadotropin-Releasing Hormone
				Corticotropin-Releasing Hormone
	Endocrinology of Pregnancy and Parturition
		Roles of Estrogens and Progesterone
		Role of Prostaglandins
		Role of Oxytocin
		Use of Placental Hormones in Genetic Screening and Pregnancy Outcomes
		Noninvasive Prenatal Testing and Microchimerism
		The “Fourth Trimester” and the Parental Brain
23 - Endocrinology of Fetal Development
	Placental Transfer of Hormones
	Ectopic Fetal Hormone Production
	Fetal Endocrine Systems
		Pituitary
			Human Hypothalamic-Pituitary Development
			Anterior Pituitary and Target Organs
			Intermediate Pituitary Lobe
			Posterior Pituitary
			Hypothalamus and Pituitary Stalk
			Genes Involved in Pituitary Disease
			Growth Hormone and Prolactin
		Adrenal
			Embryology
			Transcriptional Regulation of Adrenal Development
			Signaling Pathways in Adrenal Development
			Fetal Adrenal Steroidogenesis
			Hormonal Regulation of Adrenal Development
			The Fetal-Placental Unit
			Adrenal Insufficiency
		Thyroid Development
			Embryology
			Thyroid Hormone Biosynthesis
			Thyroid Hormone Action
			Ontogeny of Thyroid Hormone Secretion
			Genetic Regulation of Thyroid Development
			Putative Contributing Mechanisms to Thyroid Morphogenesis
			Thyroid Function in Preterm Infants
			Congenital Hypothyroidism
		Gonadal Development
			Embryology
			Fetal Sex Steroid Production
			Disorders of Sex Development
		Fetal Autonomic Nervous System
			Embryology
			Functional Development of the Sympathoadrenal System
		Endocrine Pancreas: Insulin and Glucagon
			Embryology
			Functional Development of the Endocrine Pancreas
			Pancreatic Regulation of Blood Glucose
			Neonatal Diabetes
			Hyperinsulinemic Hypoglycemia of Infancy
		Parathyroid/Calcitonin System
			Embryology
			Transcription Factors Involved in Development of ­Parathyroid Glands
			Fetal and Neonatal Calcium Metabolism
			Calcium-Sensing Receptor (CaSR) and FGF23
	Fetal Growth
		Insulin-Like Growth Factors
		Insulin
		Epidermal Growth Factor/Transforming Growth Factor
		Other Factors
	Neutralization of Hormone Actions in the Fetus
		Limitation of Hormone Secretion
		Production of Inactive Hormone Metabolites
		Neutralization of Receptor Response
	Programming of Fetal Endocrine Systems
	Transition to Extrauterine Life
		Cortisol Surge
		Catecholamine Surge
		Thermogenesis in Neonatal Brown Adipose Tissue
		Calcium Homeostasis
		Glucose Homeostasis
		Other Hormonal Adaptations
	Maternal and Fetal Medicine
24 - Disorders of Sex Development
	Development of the Reproductive Systems
		Sex Determination and Sex Differentiation
			Chromosomal Sex
				The Y Chromosome
				The X Chromosome
			Gonadal Sex
				The Bipotential Gonad
				Primordial Germ Cell Migration
				Testis Determination
				Ovary Development
			Phenotypic or Anatomic Sex
				Male Sex Differentiation
				Female Sex Differentiation
			Psychosexual Development
		Development of the Hypothalamic-Pituitary-Gonadal Axis in the Fetus
		The Hypothalamic-Pituitary-Gonadal Axis in Infancy and Childhood
			Postnatal Endocrine Changes in Boys
			Postnatal Endocrine Changes in Girls
	Disorders (Differences) of Sex Development
		Nomenclature and Classification of Disorders of Sex Development
		Sex Chromosome Disorders of Sex Development
			Klinefelter Syndrome and Its Variants
			Turner Syndrome and Its Variants
			45,X/46,XY Mosaicism and Variants
			Ovotesticular Disorders of Sex Development: 46,XX/46,XY Chimerism and Variants
		46,XY Disorders of Sex Development
			Disorders of Testis Development
				Single-Gene Disorders
				Chromosomal Rearrangements Associated With Gonadal Dysgenesis
				Syndromic Causes of 46,XY Disorders of Sex Development
				Genes Involved in Central Hypogonadism
				Potential Novel Genes and Oligogenic Effects
			Disorders of Androgen Synthesis
				Cholesterol Synthesis Defects: Smith-Lemli-Opitz Syndrome
				Luteinizing Hormone Receptor Mutations
				Steroidogenic Acute Regulatory Protein Defects
				P450 Side-Chain Cleavage Enzyme Deficiency
				3β-Hydroxysteroid Dehydrogenase/Δ4,5-Isomerase Type 2 Deficiency
				17α-Hydroxylase/17,20-Lyase Deficiency
				Cytochrome b5 Deficiency
				P450 Oxidoreductase Deficiency
				3α-Reductase Type 3 and 3α-Reductase Type 1: AKR1C2 and AKR1C4
				17β-Hydroxysteroid Dehydrogenase Type 3 Deficiency
				Steroid 5α-Reductase Type 2 Deficiency
			Disorders of Androgen Action
				Complete Androgen Insensitivity Syndrome
				Partial Androgen Insensitivity Syndrome
				Minimal or Mild Androgen Insensitivity Syndrome
				Hormone Profiles in Androgen Insensitivity Syndromes
				Molecular Pathogenesis of Androgen Insensitivity Syndromes
				Androgen Insensitivity Syndromes Without an Androgen Receptor Mutation
				Management of Androgen Insensitivity Syndromes
			Other Conditions Affecting 46,XY Sex Development
				Persistent Müllerian Duct Syndrome
				Hypospadias
				Anorchia and Cryptorchidism
				Anatomic Defects of the Pelvis and Penis
				Endocrine Disruptors
		46,XX Disorders of Sex Development
			Disorders of Ovarian Development
				Ovarian Dysgenesis
				46,XX Ovotesticular and 46,XX Testicular Disorders of Sex Development
			Disorders of Androgen Excess
				3β-Hydroxysteroid Dehydrogenase Type 2 Deficiency
				21-Hydroxylase Deficiency
				Treatment of 21-Hydroxylase Deficiency
				P450 Oxidoreductase Deficiency
				11β-Hydroxylase Deficiency
				Familial Glucocorticoid Resistance
				Aromatase Deficiency
				Maternal Androgen Excess
			Other Conditions Affecting 46,XX Sex Development
	Investigation and Management of Disorders of Sex Development
		Prenatal Diagnosis
		The Newborn With Atypical Genitalia
			History and Examination
			The Initial Approach to the Baby With Atypical Genitalia
			Support for the Parents
			Sex Designation
		Investigations for DSDs
		Chromosomal DSD
		46,XX DSD
		46,XY DSD
		Genetic Testing and DSDs
		Presentation During Childhood
		Presentation During Adolescence
		Presentation During Adulthood
		Information Sharing, Transitioning, and Adult Services
		Support Groups and Information
		Tumor Risk and DSDs
		Surgery and DSDs
		Fertility/Family Building
		DSD in Resource-Limited Countries
		Outcome Studies
	Acknowledgments
25 - Normal and Aberrant Growth in Children
	Normal Growth
		Overview
		Measurement
		Growth Charts
		Body Proportions
		Parental Target Height
		Skeletal Maturation
		Phases of Normal Growth
			Crossing Linear Percentiles of Infancy
			Constitutional Delay of Growth and Development
		Secular Changes in Height
	Endocrine Regulation of Growth
		The Hypothalamic-Pituitary Axis: Embryogenesis and Anatomy
			Growth Hormone–Releasing Hormone
			Somatostatin (SST)
		Growth Hormone
			Growth Hormone Pulsatility
			Ghrelin
			Pituitary Adenylate Cyclase–Activating Polypeptide
			Growth Hormone Secretion in Humans
			Peripheral Modulators of Growth Hormone
				Glucocorticoids
				Thyroid Hormones
				Insulin and IGF1
				Free Fatty Acids
				Adipokines
				Estrogens
				The Growth Hormone Receptor and Growth Hormone–Binding Protein
				Insulin-Like Growth Factors
					Historic Background. The IGFs (somatomedins) are a family of peptides that are, in part, GH dependent and mediate many of the an...
					IGF Genes and Protein Structure. There are two IGFs circulating in humans, IGF1 and IGF2. IGF1 is a basic peptide of 70 amino ac...
				Insulin-Like Growth Factor 1
					Gene Regulation. The human IGF1 gene (IGF1) is located on the long arm of chromosome 12 and contains at least six exons (Fig. 25...
					Serum Levels. In human fetal serum, IGF1 levels are relatively low and positively correlated with gestational age.237 There is a...
				Insulin-Like Growth Factor 2
					Gene Regulation. The gene for IGF2 (IGF2) is located on the short arm of chromosome 11, adjacent to the insulin gene, and contai...
					Serum Levels. Human newborn levels of IGF2 are typically 50% of adult levels. By 1 year of age, adult levels are attained, and t...
				Insulin-Like Growth Factor Receptors
		Function-Targeted Disruption of IGF and IGF Receptor Genes
		Insulin-Like Growth Factor–Binding Proteins
			Structure of IGFBPs
			Role of IGFBPs in IGF Physiology
				IGFBPs as Carrier Proteins
				IGFBPs as Modulators of IGF Action
			IGF-Independent Actions of IGFBPs
			Characteristics of IGFBPs 1 Through 6
		Gonadal Steroids
			Thyroid Hormone
			Glucocorticoids
	Pathologic Basis of Growth Retardation
		Disorders of the GH-IGF1 Axis
			Growth Hormone Deficiency
			The Hypothalamus
				Congenital Disorders
					Holoprosencephaly. Holoprosencephaly, which is caused by abnormal midline development of the embryonic forebrain, usually result...
					Septo-Optic Dysplasia. In its complete form, the rare syndrome of septo-optic dysplasia (SOD) combines hypoplasia or absence of ...
					HESX1. The first homozygous missense mutation (N53C) has been detected within the homeobox domain of HESX1 in two siblings born ...
					OTX2. Mutations in other genes have been associated with CNS anatomic abnormalities and hypopituitarism. OTX2 is a homeobox gene...
					SOX3. A syndrome of X-linked hypopituitarism and mental retardation involving duplications of Xq26-27 encompassing SOX3 (OMIM 31...
					SOX2. Heterozygous mutations within SOX2 in males have been associated with anophthalmia or microphthalmia and anterior pituitar...
					GLI2. Heterozygous frameshift or nonsense GLI2 mutations have been reported in patients with holoprosencephaly. In addition, non...
					PROKR2. Patients with septo-optic dysplasia with CPHD have been found to have mutations in PROKR2, a known cause of isolated idi...
				Acquired Disorders
					Inflammation of the Brain or Hypothalamus. Bacterial, viral, or fungal infections may result in hypothalamic/pituitary insuffici...
					Tumors of the Brain or Hypothalamus. Brain tumors are a major cause of hypothalamic insufficiency,408 especially midline brain t...
					Trauma of the Brain or Hypothalamus. Head trauma, resulting from boxing and various injuries, can cause IGHD or multiple anterio...
					Psychosocial Dwarfism. An extreme form of failure to thrive is termed psychosocial dwarfism or emotional deprivation dwarfism.41...
			The Anterior Pituitary
				Congenital Disorders. As many as 3% to 30% of patients with GHD have an affected parent, sibling, or child.418 Inborn errors of ...
					Combined Pituitary Hormone Deficiency. During pituitary development, a series of transcription factors are expressed in a specif...
					PITX2. PITX2 (also known as RIEG) is a member of the bicoid-like homeobox transcription factor family that is closely related to...
					SOX2. Heterozygous mutations in SOX2 (sex-determining region Y box 2) have been associated with eye abnormalities (i.e., anophth...
					LHX3. LHX3 is a member of the LIM-type homeodomain protein family of transcription factors that feature two LIM domains in their...
					LHX4. LHX4 is another LIM homeodomain protein with homology to LHX3, and it is also expressed in the developing brain, including...
					SIX6. SIX6 is a member of the SIX/sine oculis family of homeobox genes that is expressed in retina, optic nerve, hypothalamus, a...
					ISL1. ISL1 is a member of the LIM homeodomain family of transcription factors, which are characterized by two tandemly repeated ...
					PROP1. Mutations in PROP1, a paired-like homeodomain transcription factor with expression restricted to the anterior pituitary d...
					POU1F1. The POU1F1 gene (chromosome 3p11, OMIM 173110) encodes Pit1, a member of a large family of transcription factors referre...
				ARNT2
				GRP161
					Isolated Growth Hormone Deficiency. The incidence of IGHD is estimated to be 1 in every 3480 to 10,000 live births.86,547–549 In...
					IGHD Type I. IGHD type IA results primarily from large deletions, with rare frameshift and nonsense mutations of the GH1 gene th...
					IGHD Type II. IGHD type II is inherited as an autosomal dominant trait. The most common cause appears to be mutations that inact...
					IGHD Type III. IGHD type III, transmitted as an X-linked trait with associated hypogammaglobulinemia (XLA),593 has not yet been ...
					SOX3. Mutations in SOX3, a member of the SOX (SRY-related high mobility group box) family of transcription factors on Xq27.1, ha...
					Bioinactive GH. Serum GH exists in multiple molecular forms, reflecting the consequences of alternative post-transcriptional or ...
				Acquired Disorders
					Craniopharyngiomas and Other Tumors. Many tumors that impair hypothalamic function also affect pituitary secretion of GH. In add...
					Histiocytosis X. The localized or generalized proliferation of mononuclear macrophages (histiocytes) characterizes Langerhans ce...
				Growth Hormone Insensitivity
					Mutations in GHR Signaling Proteins and ALS. GH insensitivity, also known as primary IGF1 deficiency, encompasses a variety of g...
					Abnormalities of IGF1 and IGF1 Receptor Signaling. Woods and colleagues656 described a 15-year-old boy with deletion of exons 4 ...
					Inactivating Mutation of the IGF1 Gene. An adult with the same phenotype as the boy with the IGF1 deletion but with markedly ele...
					Primary Defects of IGF Transport and Clearance. Siblings from two families with high IGF1 and IGF2 levels, normal to high IGFBP3...
					Primary Defects of IGF1 Receptor Production or Responsiveness. Patients with IUGR and postnatal growth failure, microcephaly, an...
		Disorders Outside the Growth Hormone–IGF Axis
			Malnutrition
			Chronic or Systemic Diseases
				Malabsorption and Gastrointestinal Diseases
				Chronic Liver Disease
				Cardiovascular Disease
				Renal Disease
				Hematologic Disorders
				Inborn Errors of Metabolism
				Pulmonary Disease
				Chronic Inflammation and Infection
			Endocrine Disorders
				Hypothyroidism
				Diabetes Mellitus
				Cushing Syndrome: Glucocorticoid Excess
				Pseudohypoparathyroidism: Albright Hereditary Osteodystrophy
				Rickets
				Hypophosphatemic Rickets
			Osteochondrodysplasias
			Chromosomal Abnormalities
				Down Syndrome
				Turner Syndrome
				Noonan Syndrome
				Prader-Willi Syndrome
				Other Syndromes
			Small for Gestational Age
				Maternal and Placental Factors
	Pathologic Basis of Excess Growth
		Statural Overgrowth in the Fetus
			Sotos Syndrome
			Beckwith-Wiedemann Syndrome
		Postnatal Statural Overgrowth
			Tall Stature
			Obesity
			Tumors
	Evaluation and Treatment of Growth Abnormalities
		Clinical Evaluation of Growth Retardation
			History and Physical Examination
		Laboratory Testing
			Screening Tests
				Bone Age
				Prediction of Adult Height
			Tests of the GH-IGF1 Axis
				Insulin-Like Growth Factor 1
				Insulin-Like Growth Factor–Binding Protein 3
				Insulin-Like Growth Factor 2
				Growth Hormone
					Assay Limitations. One of the biggest confounders in the evaluation of GH secretion is the variability of measured GH levels acr...
					Provocative Tests. Because random GH levels cannot be used to diagnose GHD, evaluation of GH secretion requires that samples be ...
					Determination of the “Subnormal” Response to Provocative Tests. GH secretion has a continuous distribution; there is not a bimod...
					Specificity of Provocative Tests for Growth Hormone Deficiency. The data that are available suggest a low specificity for the pr...
					Sex Hormone Priming. Serum GH levels rise during puberty, with GH secretion stimulated by the rise in estrogen produced from the...
					Tests of Spontaneous Growth Hormone Secretion. Another diagnostic approach to evaluate GH secretion involves measurement of spon...
					Summary. Despite the many problems associated with GH measurement methods, there continues to be value in determining GH secreto...
				Growth Hormone–Binding Protein
				IGF1 and IGFBP Generation Tests
			Interpretation of Tests
				Neonate
				Growth Hormone Deficiency
				Growth Hormone Insensitivity
				Constitutional Delay of Growth and Development
				Genetic (Familial) Short Stature
				Idiopathic Short Stature
		Treatment of Growth Failure
			Treatment of Constitutional Delay
				Androgen (Oxandrolone and Testosterone)
				Growth Hormone
				Aromatase Inhibitor
			Treatment of Growth Hormone Deficiency
				Nomenclature and Potency Estimation
				Historical Perspective
				Treatment Regimens
				Adult Height Outcomes
				Benefits of GH Treatment Other Than Improved Growth
				Combined Pituitary Hormone Deficiencies
				Monitoring Growth Hormone Therapy
				Treatment During the Transition to Adulthood and in Adulthood
			Growth Hormone Treatment of Other Forms of Short Stature
				Prader-Willi Syndrome
				Chronic Renal Disease
				Juvenile Idiopathic Arthritis
				Turner Syndrome
				Small for Gestational Age
				Osteochondrodysplasias
					SHOX Haploinsufficiency and Léri-Weill Syndrome. Patients with mutations or deletions of the SHOX gene have variable degrees of ...
					Turner Syndrome and Langer Mesomelic Dysplasia. Homozygous mutation of the SHOX gene results in the Langer type of mesomelic dwa...
				Noonan Syndrome
				Idiopathic Short Stature (Subtle Errors Throughout the Growth Axis)
				Miscellaneous Causes of Growth Failure
					Down Syndrome. The encouraging results of GH trials in TS led to studies of GH therapy in children with Down syndrome. In severa...
					Normal Aging and Other Catabolic States. Detailed consideration of the potential use of GH in normal aging is beyond the scope o...
			Adverse Effects of Growth Hormone
				Development of Leukemia and Other Malignancies
				Recurrence of Central Nervous System Tumors
				Development of Subsequent Neoplasms
				Pseudotumor Cerebri
				Slipped Capital Femoral Epiphysis
				Scoliosis
				Diabetes Mellitus
				Miscellaneous Side Effects1307,1442,1516
				The Question of Long-Term Cancer Risk
				Long-Term Mortality with GH Treatment
			IGF1 Treatment
			Other Treatments to Promote Growth
				Aromatase Inhibitors
				Oxandrolone
		Diagnosis and Treatment of Excess Growth and Tall Stature
			Diagnosis
			Treatment
26 - Physiology and Disorders of Puberty
	Puberty and Evolution
	Fetal Origins of Adult Disease
	Determinants of the Age of Puberty and Menarche
		The Secular Trend in Puberty and Menarche
			The Developed World
			The Developing World
			Factors Affecting the Age of Puberty and Menarche
				Stress and Puberty
				Genetic Effects on Puberty and Menarche
				Cancer and Age of Puberty
				Other Factors
		The Comorbid Conditions of Early Puberty
		National Trends in Pubertal Development
			Limits of Normal Pubertal Development
	Secondary Sexual Characteristics and Physical Changes of Puberty
		Female Development
			Ovarian Development
			Menarche and Teenage Pregnancy
		Male Development
			Male Testicular Development in Puberty
			Spermatogenesis
		Other Physical and Biochemical Changes of Puberty
		Adolescent Growth
			Pubertal Growth Spurt
			Bone Age
			Skeletal Density
			Body Composition
			Obesity, Puberty, and the Metabolic Syndrome
				Serum Lipids in Normal Puberty and in Obesity and the Metabolic Syndrome
				Insulin and Insulin Resistance
				Blood Pressure
		Central Nervous System Anatomy, Function, Psychology, and Electroencephalographic Rhythm in Puberty
		Sleep Patterns in Puberty
		Characteristics of Adolescence
		Behavior and Normal Puberty
			Mood and Self-Image in Puberty
			Behavior in Variations of the Normal Age at Onset of Puberty
			Risk-Taking Behavior
			Sexuality During Puberty
	Hormonal and Metabolic Changes in Puberty
		Gonadotropins
		Gonadal Steroids
			Testosterone
			Estrogens
		Protein Products of the Gonads
			Inhibin, Activin, and Follistatin
			Antimüllerian Hormone
		Adrenal Androgens
		Testosterone-Binding Globulin
		Prolactin
		Insulin-Like 3 Protein
		Prostate-Specific Antigen
		Hormonal Control of the Pubertal Growth Spurt
			Gonadal Steroids159,160
			Growth Hormone and Growth Factors
			Growth Hormone–Binding Protein
			Insulin-Like Growth Factor Type 1
			Other Hormones
	Central Nervous System and Puberty
		Pattern of Gonadotropin Secretion
			Tonic Secretion
			Pulsatile Secretion
				The GnRH Pulse Generator
					GnRH. Generation of the GnRH pulse is an intrinsic property of the GnRH neurosecretory neuronal network, and other factors modul...
					Gonadotropin-Inhibitory Hormone. Gonadotropin-inhibitory hormone (GnIH), a peptide first described in quail but now homologues o...
					Kisspeptins and KISS1R. Kisspeptins and their receptors (KISS1R or GRP54) in the CNS hypothalamic-pituitary-gonadal axis play a ...
		Ontogeny
			Human Fetus
			Sheep Fetus
			Human Neonate and Infant291,326
			Neural Control
		Timing and Onset of Puberty
			Genetic Neural Control
			Nutrition and Metabolic Control
			Mechanisms of Control
				Gonadal Steroid–Dependent Negative Feedback Mechanism
				Gonadal Steroid–Independent (Intrinsic) Central Nervous System Inhibitory Mechanism
				Interaction of the Negative Feedback Mechanism and the Intrinsic Central Nervous System Inhibitory Mechanism
				Potential Components of the Intrinsic Central Nervous System Inhibitory Mechanism
			Sleep-Associated Luteinizing Hormone Release and Onset of Puberty
			Pituitary and Gonadal Sensitivity to Tropic Stimuli
			Maturation of Positive Feedback Mechanism
			Overview of Current Concept
	Adrenal Androgens and Adrenarche
		Nature and Regulation of Adrenal Androgens
		Adrenal Androgens and Puberty
	Disorders of Puberty
		Delayed Puberty and Sexual Infantilism
			Idiopathic or Constitutional Delay in Growth and Puberty
			Hypogonadotropic Hypogonadism: Sexual Infantilism Related to Gonadotropin Deficiency
				Isolated Hypogonadal Hypogonadism
					Kallmann Syndrome. Anosmia or hyposmia resulting from agenesis or hypoplasia of the olfactory lobes or sulci is associated with ...
						KAL1. In classic, X-linked KAL1, fetal GnRH neurosecretory neurons do not migrate from the olfactory placode to the medial basal...
						KAL2. The autosomal dominant form is known as Kallmann syndrome type 2 (KAL2), and the associated gene is fibroblast growth fact...
						KAL3. Apparent autosomal recessive inheritance characterizes other kindreds with Kallmann syndrome type 3 (KAL3), for which the ...
						Other Forms of Kallmann Syndrome. The human equivalent of the mouse nasal embryonic GnRH factor gene (Nelf) is NELF; a mutation ...
					Other Forms of Isolated Hypogonadotropic Hypogonadism. Only about 15% of normosmic hypogonadotropic patients have a definable ge...
						Gonadotropin-Releasing Hormone Gene Mutations. The GnRH gene (GNRH1) would seem a likely candidate for the cause of hypogonadotr...
						Gonadotropin-Releasing Hormone Receptor Mutations. Mutations of the gene encoding the type 1 GnRH receptor (GNRHR, gene map locu...
						KISS1/KISS1R Axis Mutations. The KISS1/KISS1R axis plays a role in the increased amplitude of GnRH signaling in puberty. KISS1/K...
						X-Linked Congenital Adrenal Hypoplasia and Hypogonadotropic Hypogonadism. A rare deletion or mutation in the dosage-sensitive se...
						Isolated Luteinizing Hormone Deficiency. Isolated LH deficiency (fertile eunuch syndrome) is associated with deficient testoster...
						Isolated Follicle-Stimulating Hormone Deficiency. Homozy-gous or compound heterozygous mutations in the FSH β-subunit have been ...
						Follicle-Stimulating Hormone Receptor Mutations. Hypergonadotropic hypogonadism is noted with rare mutations in FSH receptors.54...
				Developmental Defect of the Midline
				Idiopathic Hypopituitary Dwarfism
				Miscellaneous Conditions
					Prader-Willi Syndrome. Prader-Willi syndrome is an autosomal dominant disorder that combines a tendency for intrauterine growth ...
					Laurence-Moon and Bardet-Biedl Syndromes. The Laurence-Moon syndrome and the Bardet-Biedl syndrome were previously separated as ...
					Functional Gonadotropin Deficiencies and Other Chronic Conditions. The effects of malnutrition, which can lead to functional hyp...
					Other Endocrine Conditions and Puberty. Hypothyroidism may delay the onset of puberty or menarche (except in extreme cases in wh...
					Anorexia Nervosa and Variants.580,581,990
						Anorexia Nervosa. Anorexia nervosa,582 a common cause of gonadotropin deficiency in adolescence, is a functional disorder. Preva...
						Bulimia Nervosa. Bulimia nervosa is now separated from the diagnosis of anorexia nervosa582; DSM-IV diagnostic criteria are as f...
						Exercise, Hypo-ovarianism, and Amenorrhea: The Female Athlete Triad. In 1992, the American College of Sports Medicine defined th...
				Other Causes of Delayed Puberty
				Central Nervous System Tumors
					Craniopharyngioma. Craniopharyngioma is a rare embryonic malformation of nonglial origin in childhood (0.5–2 new cases per 1 mil...
					Other Extrasellar Tumors
						Germinomas. Germinomas (i.e., pinealomas, ectopic pinealomas, atypical teratomas, or dysgerminomas) and other germ cell tumors o...
						Pituitary Adenomas. Only 2% to 6% of all surgically treated pituitary tumors occur in childhood and adolescence, with about 1 in...
					Other Central Nervous System Disorders Leading to Delayed Puberty
						Langerhans Cell Histiocytosis. Langerhans cell histiocytosis (i.e., Hand-Schüller-Christian disease or histiocytosis X) is a clo...
						Postinfectious Inflammatory Lesions of the Central Nervous System, Vascular Abnormalities, and Head Trauma. Tuberculous or sarco...
						Irradiation of the Central Nervous System. Irradiation of the CNS for treatment of tumors, leukemia, or neoplasms of the head an...
							Fröhlich Syndrome. Fröhlich syndrome or adiposodysgenesis is a constellation of endocrine abnormalities, combining findings of o...
				Hypergonadotropic Hypogonadism: Sexual Infantilism Caused by Primary Gonadal Disorders
					Boys
						Klinefelter Syndrome and Its Variants (see Chapter 24). Klinefelter syndrome (i.e., syndrome of seminiferous tubular dysgenesis)...
						Behavior and Development in Klinefelter Syndrome. Neurobehavioral abnormalities, primarily in language, speech, learning, and fr...
						Other Aspects of Klinefelter Syndrome. Conditions associated with Klinefelter syndrome include aortic valvular disease and ruptu...
						Other Forms of Primary Testicular Failure
							Cancer Survivors. Chemotherapy Chemotherapy and direct radiotherapy affect testicular function, and as more children survive wit...
						Radiation Therapy. Radiation to the gonads can cause primary testicular failure, usually resulting in azoospermia, although norm...
						Testicular Biosynthetic Defects. The 46,XY disorder of sex development is caused by 17α-hydroxylase/17,20-lyase deficiency resul...
						Luteinizing Hormone Resistance. Presumptive evidence of LH resistance caused by an LH receptor abnormality on the Leydig cell wa...
						Anorchia and Cryptorchidism. Cryptorchidism is the condition in which one or both testes have not reached the bottom of the scro...
						Small for Gestational Age. SGA predisposes males to reproductive problems and is also associated with the TDS. Males born SGA te...
					Girls
						Syndrome of Gonadal Dysgenesis and Its Variants.622. The most common form of hypergonadotropic hypogonadism in the female is the...
						45,X Turner Syndrome.993 Short stature and sexual infantilism are typical features of sex chromatin–negative 45,X gonadal dysgen...
						Behavior and Development of Turner Syndrome. Counseling and a peer support group are exceedingly important components of long-te...
						Sex Chromatin–Positive Variants of the Syndrome of Gonadal Dysgenesis. Mosaicism of 45,X/46,XX; 45,X/47,XXX; or 45,X/46,XX/47,XX...
						Sex Chromatin–Negative Variants of Gonadal Dysgenesis. These variants include 45,X/46,XY mosaicism and structural abnormalities ...
						46,XX and 46,XY Gonadal Dysgenesis. The term pure gonadal dysgenesis refers to phenotypic females with sexual infantilism and a ...
						Familial and Sporadic 46,XX Gonadal Dysgenesis and Its Variants. The usual phenotype of 46,XX gonadal dysgenesis includes normal...
						Familial and Sporadic 46,XY Gonadal Dysgenesis and Its Variants. A phenotype that includes female genitalia with or without clit...
						Other Causes of Primary Ovarian Failure. The prevalence of primary ovarian failure is increasing as a consequence of the long-te...
						Chemotherapy. Successful treatment of childhood acute lymphoblastic leukemia has become commonplace. Chemotherapy and radiation ...
						Radiation Therapy. Ovarian transposition, moving the ovaries out of the radiation field if they are not the target of therapy, b...
						Autoimmune Oophoritis. Premature menopause may occur at any age before the normal climacteric and has been reported in adolescen...
						Homozygous Galactosemia. Homozygous galactosemia due to mutation in the galactose-1-phosphate uridylyltransferase (GALT) gene is...
						Haploinsufficiency of the FOXL2 Gene. A rare autosomal dominant disorder involving eyelid dysplasia and premature ovarian failur...
						Congenital Disorders of Glycosylation-1: Carbohydrate-Deficient Glycoprotein Syndrome Type Ia. The congenital disorders of glyco...
						Follicle-Stimulating Hormone Receptor Resistance: Gene Mutations and Hypergonadotropic Hypogonadism. The FSH receptor is a membe...
						Luteinizing Hormone and Human Chorionic Gonadotropin Resistance. LH/hCG resistance due to mutations in the gene encoding the sev...
						Polycystic Ovary Syndrome. PCOS, or functional ovarian hyperandrogenism, does not delay the onset of puberty but often delays me...
						Noonan Syndrome. Individuals with Noonan syndrome (i.e., pseudo-Turner syndrome, Ullrich syndrome) have webbed neck, ptosis, dow...
						Frasier Syndrome. Germline mutations in exon 8 or 9, coding for zinc fingers 2 or 3 of the Wilms tumor suppressor gene, WT1, lea...
						Williams-Beuren Syndrome. Williams-Beuren syndrome is a microdeletion disorder, or contiguous-gene-deletion disorder caused by d...
		Diagnosis of Delayed Puberty and Sexual Infantilism
		Treatment of Delayed Puberty and Sexual Infantilism
		Sexual Precocity994
			Central Precocious Puberty: Complete Isosexual Precocity
				Idiopathic True or Central Precocious Puberty159,160,316,423,726,727
				Gain-of-Function Mutations as Cause of Central Precocious Puberty
					KISS and KISSIR/GRP54 Mutations
						KISS Mutations. Whereas inactivating mutations in the KISS1R receptor cause hypogonadotropic hypogonadism, recently the first de...
				Loss-of-Function Mutations as Cause of Central Precocious Puberty
					MKRN3. Ten different loss-of-function mutations of MKRN3, an imprinted gene located on the long arm of chromosome 15q11.2 in the...
					DLK1. Delta-like 1 homolog (DLK1) is another paternally imprinted gene recently reported to be associated with precocious pubert...
				Central Nervous System Tumors Causing True Precocious Puberty
					Hamartomas of the Tuber Cinereum. Hamartomas are congenital malformations composed of a heterotopic mass of nervous tissue conta...
					Neurofibromatosis Type 1. Neurofibromatosis type 1 (NF1 or von Recklinghausen disease) is associated with a propensity to develo...
				Other Central Nervous System Conditions
					Arachnoid Cysts. Arachnoid cysts arising de novo, after infection or after surgery, can cause premature sexual development, poss...
					Other Central Nervous System Abnormalities. Other CNS abnormalities associated with CPP but without demonstrable lesions on imag...
				Miscellaneous Causes
					Central Precocious Puberty in Children Adopted From Developing Countries. There was a 15-fold to 20-fold increased prevalence of...
					True Precocious Puberty After Virilizing Disorders. Correction of long-standing virilization may be followed by development of C...
					Marfan Syndrome. Marfan syndrome may be associated with tall stature and early PHV and menarche compared with North American ave...
				Management of Central Precocious Puberty
					Medroxyprogesterone Acetate and Cyproterone Acetate. Medroxyprogesterone and cyproterone reversed or arrested the progression of...
					Superactive Gonadotropin-Releasing Hormone Agonists. The GnRH agonists, synthetic analogues of the amino acid sequence of the na...
						Adverse Effects. Rare reactions to GnRH agonists include local and systemic allergic reactions, including asthmatic episodes whe...
					Other Treatment for Precocious Puberty. The GnRH agonists are useful in conjunction with GH in the management of organic or neur...
					Psychosocial Aspects. Psychologic management is a critical aspect of the care of children with CPP. With the advanced physical m...
			Peripheral Precocious Puberty or Incomplete Isosexual Precocity: Gonadotropin-Releasing Hormone–Independent Sexual Precocity995
				Boys
					Chorionic Gonadotropin–Secreting Tumors. Several types of germ cell tumors secrete hCG, which may cross-react in some polyclonal...
						Precocious Androgen Secretion Caused by the Adrenal Gland
							Virilizing Congenital Adrenal Hyperplasia. Virilizing CAH caused by a defect in 21-hydroxylation (CYP21 deficiency) leads to ele...
							Virilizing Adrenal Tumor. Virilizing adrenal carcinomas or adenomas secrete large amounts of DHEA and DHEAS and, on occasion, te...
							NR0B1 (DAX1) Gene Mutations. Two cases of NR0B1 frameshift mutations demonstrated adrenal failure and GISP that were suppressibl...
							Leydig Cell Tumor. Testicular tumors are rare in childhood, representing 1% to 2% of all pediatric solid tumors, and Leydig cell...
							Pituitary Gonadotropin–Independent Familial Premature Leydig Cell and Germ Cell Maturation: Familial or Sporadic Testotoxicosis....
							Gonadotropin-Independent Sexual Precocity and Pseudohypoparathyroidism Type Ia. A mutation in Gsα can constitutively activate or...
				Girls
					Autonomous Ovarian Follicular Cysts. The most common childhood estrogen-secreting ovarian mass and ovarian cause of sexual preco...
					Ovarian Tumors. Ovarian tumors are the most common genitourinary tumors of girls,847,848 accounting for about 1% of all tumors i...
					Peutz-Jeghers Syndrome. Peutz-Jeghers syndrome, an autosomal dominant syndrome, is usually caused by mutations in the gene locat...
					Adrenal Tumors. Adrenocortical tumors are rare in childhood (0.6% of all childhood tumors and 0.3% of all malignant childhood tu...
				Boys and Girls
					McCune-Albright Syndrome. McCune-Albright syn­drome846,1003 occurs about twice as often in girls than in boys; it is sporadic an...
					Juvenile Hypothyroidism. Long-standing untreated primary hypothyroidism, usually a consequence of Hashimoto thyroiditis, is an u...
					Iatrogenic Sexual Precocity and Endocrine Disruptors. Prepubertal children are remarkably sensitive to exogenous gonadal steroid...
			Diagnosis of Sexual Precocity
			Contrasexual Precocity: Feminization in Boys and Virilization in Girls
				Boys
					Aromatase Excess Syndrome. Gynecomastia in prepubertal boys can be caused by increased extraglandular aromatization of C19 stero...
					Feminizing Testicular Tumors. Feminizing testicular tumors may cause gynecomastia in boys younger than 6 years of age who have t...
				Girls
					Adrenal Causes of Virilization. CAH resulting from 21-hydroxylase or 11β-hydroxylase deficiency or from androgen-producing tumor...
					Syndrome of Glucocorticoid Resistance. The syndrome of glucocorticoid resistance has variable manifestations. Some patients demo...
					Virilizing Ovarian Tumors. Arrhenoblastoma, also called Sertoli tumor of the ovary, is the most common virilizing ovarian tumor,...
			Variations of Pubertal Development
				Premature Thelarche
				Premature Isolated Menarche
				Premature Adrenarche
				Polycystic Ovary Disease958,959
				Adolescent Gynecomastia970
				Macroorchidism
27 - Hormones and Athletic Performance
	Effect of Athletic Performance onHormonal Systems
		Catecholamines
			Fluid Homeostasis–Vasopressin–Renin-Angiotensin-Aldosterone System
		Hypothalamus-Pituitary-Adrenal Axis
			Glucocorticoids
			Response to Endurance Exercise
			Response to Resistance Exercise
			Mineralocorticoids
			Endorphins
		Hypothalamic-Pituitary-Gonadal Axis
			Male Gonadal Axis
			Female Gonadal Axis
		Prolactin
		GH/IGF1 Axis
		Hypothalamus-Pituitary-Thyroid Axis
		Insulin and Glucose Metabolism
		Erythropoietin
		Anabolic Androgenic Steroids
			Adverse Effects
			Detection
		Growth Hormone
			Adverse Effects
			Detection
		GH Secretagogues
		Insulin-like Growth Factor 1
			Adverse Effects
			Detection
		Insulin
			Adverse Effects
			Detection
		Erythropoietin and the Erythropoietin System
			Adverse Effects
			Detection
		Glucocorticosteroids
			Adverse Effects
			Detection
28 - Endocrinology and Aging
	Aging and Physical Frailty
	The Endocrinology of Aging
	Menopause
		Perimenopausal Use of Hormone Therapy
		Long-Term Hormone Replacement Therapy
		Selective Estrogen Receptor Modulators
			Androgen Replacement
		HT, SERMs, or No Treatment?
	Andropause Versus Late-Onset Hypogonadism
		Role of Testosterone During Aging
		Testosterone Replacement Therapy
			Which Elderly Men Should Be Treated?
	Adrenopause
		Role of DHEA During Aging
		DHEA Replacement Therapy
		Conclusions
	Somatopause
		Role of GH and IGF1 During Aging
		GH Therapy
		Conclusions
	The Concept of Successful Aging
29 - Hormones and Disorders of Mineral Metabolism
	Basic Biology of Mineral Metabolism: Roles of the Mineral Ions
	Parathyroid Hormone
		Parathyroid Gland Biology
			Parathyroid Hormone Biosynthesis
			Parathyroid Hormone Secretion
			Regulation of the Parathyroid Hormone Gene
			Regulation of Parathyroid Cell Number
		Parathyroid Gland Development
		Metabolism of Parathyroid Hormone
		Actions of Parathyroid Hormone
			Actions of Parathyroid Hormone on the Kidney
				Stimulation of Calcium Reabsorption
				Inhibition of Phosphate Transport
				Other Renal Effects of Parathyroid Hormone
			Actions of Parathyroid Hormone on Bone
				PTH Increases Bone Formation
				PTH Increases Bone Resorption
			Molecular Basis of Parathyroid Hormone Action
				Parathyroid Hormone and Parathyroid Hormone–Related Protein Receptors
				Functional Implications of Parathyroid Hormone Structure
				Activation of Second Messengers
				Second Messengers and Distal Effects of Parathyroid Hormone
				Target Cell Responsiveness to Parathyroid Hormone
		Parathyroid Hormone–Related Protein
			Gene and Protein Structure
			Functions of Parathyroid Hormone–Related Protein
	Calcitonin
		Synthesis and Secretion
		Calcitonin Family: Calcitonin Gene-Related Peptide, Amylin, Adrenomedullin, Calcitonin Receptor–Stimulating Peptides, and Interm...
		Calcitonin in Human Disease
		Therapeutic Uses
	Vitamin D
		Metabolism of Vitamin D
		Actions of Vitamin D
			Vitamin D Receptors
			Intestinal Calcium Absorption
				Entry Into the Enterocyte
				Transcellular Transport
				Exit From the Enterocyte
			Actions on the Parathyroid Gland
			Actions on Bone
			Other Actions of Vitamin D
		Vitamin D Analogs
	Fibroblast Growth Factor-23
		FGF23 in Human Disease
		Actions of FGF23
		Regulation of FGF23
	Calcium and Phosphate Homeostasis
	Laboratory Assessment of Mineral Metabolism
		Parathyroid Hormone
		Parathyroid Hormone–Related Protein
		Calcitonin
		Vitamin D Metabolites
		Fibroblast Growth Factor-23
	Hypercalcemic Disorders
		Parathyroid-Dependent Hypercalcemia
			Primary Hyperparathyroidism
				Classic Primary Hyperparathyroidism
				Contemporary Primary Hyperparathyroidism
				Etiology and Pathogenesis
				Inherited Primary Hyperparathyroidism
				Management of Primary Hyperparathyroidism
			Familial Hypocalciuric Hypercalcemia
			Lithium Toxicity
		Parathyroid-Independent Hypercalcemia
			Hypercalcemia of Malignancy
				Local Osteolytic Hypercalcemia
				Humoral Hypercalcemia of Malignancy
			Vitamin D Intoxication
			Sarcoidosis and Other Granulomatous Diseases
			CYP24A1 Loss of Function
			Hyperthyroidism
			Vitamin A Intoxication
			Adrenal Insufficiency
			Thiazide Diuretics
			Milk-Alkali Syndrome
			Immobilization
			Renal Failure
			Williams Syndrome
			Jansen Metaphyseal Chondrodysplasia
		Approach to the Hypercalcemic Patient
		Causes of Severe Hypercalcemia
		Clinical Features of Severe Hypercalcemia
		Management of Severe Hypercalcemia
			Volume Repletion
			Bisphosphonates
			Denosumab
			Calcitonin
			Other Approaches to Treatment of Severe Hypercalcemia
	Hypocalcemic Disorders
		Clinical Presentation
		Parathyroid-Related Disorders
			Congenital or Inherited Parathyroid Disorders
			Abnormalities in the PTH Gene
			Destruction of the Parathyroid Glands
			Impaired PTH Secretion
			Pseudohypoparathyroidism
		Vitamin D–Related Disorders
			Vitamin D Deficiency
			Accelerated Loss or Inactivation of Vitamin D
			Impaired 25-Hydroxylation of Vitamin D
			Impaired 1α-Hydroxylation of 25-Hydroxyvitamin D
			Target Organ Resistance to 1,25(OH)2D3
		Other Causes of Hypocalcemia
			Excessive Deposition Into the Skeleton
			Impaired Resorption
			Chelation
			Neonatal Hypocalcemia
		HIV
		Critical Illness
		Treatment of Hypocalcemia
	Disorders of Phosphate Metabolism
		Hyperphosphatemia
		Hypophosphatemia
			Etiology
		Continued
			Clinical Features
			Treatment
	Disorders of Magnesium Metabolism
		Hypermagnesemia
		Hypomagnesemia
			Etiology
				Intestinal Causes of Hypomagnesemia
				Renal Causes of Hypomagnesemia
				Other Causes of Hypomagnesemia
			Consequences of Hypomagnesemia
			Therapy of Hypomagnesemia
30 - Osteoporosis: Basic and Clinical Aspects
	Historical Context
	Skeletal Biology
		Structure and Function of the Skeleton
		Embryology and Anatomy
			Bone Matrix and Mineral
			Collagen Synthesis
			Mineralization
			Collagen Degradation by Osteoblasts and Osteocytes
			Bone Lining Cells, Osteoblasts, and Osteocytes
			Osteoclast Differentiation and Function
	Bone Remodeling and Its Regulation
		Overview of Remodeling
		Local Regulators of Remodeling
			Cytokines
			TGFα and Epidermal Growth Factor
			Prostaglandins
			Peptide Growth Factors
				Fibroblast Growth Factors
				Platelet-Derived Growth Factors, Vascular Endothelial Growth Factors, Hypoxia-Inducible Factors, and Reactive Oxygen Species
				Insulin-Like Growth Factors
				Transforming Growth Factor β
				BMPs and Wnt Proteins
		Systemic Hormones and Bone Remodeling
			Calcium-Regulating Hormones
				Parathyroid Hormone
				Vitamin D
				Calcitonin
			Other Systemic Hormones That Influence Remodeling
				Growth Hormone
				Glucocorticoids
				Thyroid Hormones
				Insulin
				Gonadal Hormones
	Epidemiology of Osteoporosis and Fractures
		Fractures
			Hip Fractures
			Vertebral Fractures
			Wrist Fractures
			Other Types of Fractures
		Clinical Assessments of Osteoporosis
			Dual-Energy X-Ray Absorptiometry
			Trabecular Bone Score
			Quantitative Computed Tomography
			Bone Turnover Markers
			Bone Biopsy
		Fracture Epidemiology
		Continued
			Clinical Risk Factors and Their Combination With BMD
			Prevalence of Osteoporosis and Incidence of Fractures in the Population
	Pathogenesis of Osteoporosis
		Gonadal Deficiency
			Estrogen
			Androgens
		Age-Related Bone Loss
		Secondary Osteoporosis
			Glucocorticoid-Induced Bone Loss
			Osteoporosis Associated With Diabetes Mellitus
		Factors That Impair Peak Bone Acquisition
		Genetic Factors That Determine Peak Bone Mass
	Approach to Management of Osteoporosis
		General Measures
			Diet
				Calcium
				Vitamin D
			Physical Activity
			Lifestyle
		Pharmacologic Approaches to the Treatment of Osteoporosis
			Antiresorptive Agents
				Estrogen
				Selective Estrogen Receptor Modulators
				Bisphosphonates
				Calcitonin
				Strontium Ranelate
				Denosumab
				Cathepsin K Inhibitors
			Anabolic Agents
				Parathyroid Hormone
				PTH-Related Protein
				Future Anabolic Agents
				Monoclonal Antibodies to Sclerostin
31 - Rickets and Osteomalacia
	Introduction
	Historical Perspective
		Rickets
		Osteomalacia
	Epidemiology and Demographics
	Bone Remodeling and Mineralization
		Definition and Histologic Evolution of Osteomalacia
	Pathogenesis of Rickets and Osteomalacia
		Calcium-Deficiency Rickets
		Phosphate-Deficiency/Depletion Rickets and Osteomalacia
	Clinical Manifestations of Classical Rickets and Osteomalacia
		Bone Pain
		Muscle Weakness
		Skeletal Deformities and Fractures
		Biochemical Changes
		Radiologic Imaging Features
		Bone Mineral Density
	Treatment of Nutritional Rickets and Osteomalacia
	Rickets Due to Genetic Disorders of Vitamin D Metabolism
		Vitamin D–Dependent Rickets Types 1A, 1B, and 2
		Hereditary Hypophosphatemic Rickets and Osteomalacia
			Autosomal Dominant and Recessive Rickets
			X-Linked Recessive Hypophosphatemic Rickets
			X-Linked Hypophosphatemic Rickets and Osteomalacia
		Radiologic and Biochemical Findings
		Treatment of Hereditary Hypophosphatemic Rickets and Osteomalacia
			Standard Treatments
			Novel Treatments
			Long-Term Management
	Tumor-Induced Osteomalacia
	Drug-Induced Osteomalacia
	Conditions That Resemble Rickets and Osteomalacia
	Concluding Remarks
	Acknowledgments
32 - Kidney Stones
	Epidemiology of Stone Formation
	Pathogenesis of Stone Formation
		Physiology
		Diet
		Pathogenesis of Idiopathic Hypercalciuria
			Calcium Homeostasis
			Potential Mechanisms for the Development of IH
			Human Data
			Genetic Hypercalciuric Stone-Forming Rats
			Genetics of IH in Humans
			Other Genetic Causes of Stones and Nephrocalcinosis
			X-Linked Hypercalciuric Nephrolithiasis (Dent Disease and Others)
			Bartter Syndrome
			Familial Hypomagnesemia With Hypercalciuria and Nephrocalcinosis
			Distal Renal Tubular Acidosis
			Hereditary Hypophosphatemic Rickets With Hypercalciuria
			Primary Hyperoxaluria and Cystinuria
	Clinical Presentation and Evaluation
		Metabolic Evaluation of Stone Formers
		The Basic Evaluation
			History
				Stone History
				Medical History
				Family History
			Medications
			Lifestyle and Diet
			Physical Examination
			Laboratory Tests
			Stone Analysis
			Radiologic Evaluation
		The Complete Evaluation
	Therapy
		Surgical Treatment
		Medical Expulsive Therapy
		Medical Preventative Therapy
			Nonspecific Therapy
			Specific Therapy Matched to Specific Pathogenesis
				Calcium Stones
					Hypercalciuria. Patients with persistent hypercalciuria often benefit from a thiazide diuretic. This class of drugs is inexpensi...
					Hyperoxaluria. Oxalate is produced predominantly by endogenous metabolism of glyoxylate and, to a lesser extent, by ascorbic aci...
						Dietary Oxaluria. Dietary oxaluria results in urinary oxalate levels that are mildly elevated (40–60 mg/day). Many high-oxalate ...
						Enteric Oxaluria. Enteric oxaluria results in higher urinary oxalate levels (60–100 mg/day) than dietary hyperoxaluria. GI malab...
						Primary Hyperoxaluria. Primary hyperoxaluria (PHO) leads to nephrolithiasis because of hepatic enzyme deficiencies that lead to ...
					Hyperuricosuria. Up to 15% of patients with hyperuricosuria have calcium stones. In contrast to patients with pure calcium oxala...
					Hypocitraturia. Citrate, by combining with calcium to form a soluble complex, reduces calcium oxalate and calcium phosphate prec...
					Renal Tubular Acidosis. dRTA (type 1) is a disorder in which distal tubular hydrogen ion excretion is impaired, resulting in a n...
					Nephrocalcinosis. Nephrocalcinosis is a process in which calcium is deposited in the renal parenchyma.6 There are two forms: dys...
				Uric Acid Stones
				Struvite Stones
					Urease-Producing Bacteria. The formation of struvite stones depends on the presence of both ammonium ions and an alkaline urinar...
					Therapy for Struvite Stones. To eradicate struvite stones, early and aggressive medical and urologic management is required.237 ...
				Cystine Stones
					Therapy for Cystine Stones. The aim of treatment is to lower the urinary cystine concentration below the limits of solubility (∼...
33 - Physiology of Insulin Secretion
	Introduction
	Neural Regulation of Beta-Cell Function
	Beta-Cell Mass
	Beta-Cell Insulin Content
	Insulin Secretion Versus Plasma Insulin
	Characteristics of Insulin Secretion In Vivo
	Modes of Beta-Cell Response
	Insulin Secretion in the Fasting State
	Insulin Secretory Response to Intravenous Glucose
		Various formats of intravenous glucose administration have been used to gauge beta-cell response independently of gastrointestin...
		Hyperglycemic Clamp and Biphasic Insulin Secretion
		Intravenous Glucose Tolerance Test
		Graded Glucose Infusion Test and Beta-Cell Dose Response
	Slow Beta-Cell Response Modes and Adaptation Mechanisms
	Insulin Secretory Response to Oral Stimuli
	Insulin Secretion and Insulin Sensitivity
	Genetic Influences on Insulin Secretion
	Insulin Secretion, Insulin Action, and Glucose Homeostasis
34 - Pathophysiology of Type 2 Diabetes Mellitus
	Epidemiology
	Pathogenesis
		Genetic Factors in the Development of Type 2 Diabetes Mellitus
			Monogenic Forms of Diabetes Associated With Insulin Resistance
				Mutations in the Insulin Receptor
				Lipodystrophic Diabetes
			Genetics of the Polygenic Forms of Type 2 Diabetes Mellitus
				Insulin Receptor Substrate 1 Gene
				Transcription Factor 7–Like 2 Gene
				KATP Channel Genes: KCNJ11 and ABCC8
				Peroxisome Proliferator-Activated Receptor γ Gene
				Hepatocyte Nuclear Factor 4α Gene
				Kruppel-like Factor 14 (KLF14)
			Diabetes Genes Identified by Genome-Wide Association Studies
		Epigenetic Risk of Diabetes
	Insulin Signaling
		Downstream Events After Insulin Receptor Phosphorylation
		Tissue-Specific Actions of Insulin
			Mechanisms of Insulin-Mediated Glucose Uptake in Muscle and Fat
			Insulin Regulation of Lipolysis and Lipogenesis
			Insulin Regulation of Hepatic Carbohydrate Metabolism
			Expanding Collection of Insulin-Sensitive Tissues
				Insulin Signaling in the Central Nervous System
	Insulin Resistance and the Risk of Type 2 Diabetes Mellitus
		Insulin Resistance
		Obesity and Type 2 Diabetes Mellitus
			Hyperinsulinemia and Insulin Resistance
			Nutrient Overload and Insulin Resistance
			Adipose Tissue and Insulin Resistance
			Ectopic Lipid Accumulation
			Endoplasmic Reticulum Stress/Unfolded Protein Response
			Innate Immunity
			Mitochondrial Abnormalities
		Skeletal Muscle Insulin Resistance
			Fatty Acid Metabolism in Skeletal Muscle
			Glucose Influence on Skeletal Muscle Fatty Acid Metabolism
		Circadian Rhythms, Obesity, and Insulin Resistance
		Role of the Gut Microbiome and Metabolome in Diabetes and Insulin Resistance
	Special Conditions That Induce Insulin Resistance
		Gestational Diabetes
		Drugs and Stress-Induced Insulin Resistance
			Glucocorticoid-Induced Insulin Resistance
			Post-Transplant Diabetes Mellitus
			Inflammation and Inflammatory Cytokines
			Human Immunodeficiency Virus Infection
			Statins
			Glucotoxicity, Glucosamine
			Postoperative Hyperglycemia
35 - Therapeutics of Type 2 Diabetes Mellitus
	Epidemiology
		Diagnostic Criteria
	General Approaches to Management
		Public Health Measures
		Primary Care Management
		Complex Diabetes Care
		Screening
		Interventional Study Results
		Glycemic Treatment Targets
		Monitoring of Glucose During Treatment
			Hemoglobin A1c
			Self-Monitoring of Blood Glucose
			Continuous Glucose Monitoring
			Hypoglycemia
		Lifestyle Interventions
		Diabetes Self-Management Education and Support
			Medical Nutrition Therapy
			Physical Activity and Exercise
			Addressing Psychosocial Needs
	Glucose-Lowering Pharmacotherapy
		Oral Agents
			Biguanides
			Insulin Secretagogues
			Sulfonylureas
			Glinides
			Thiazolidinediones
			DPP4 Inhibitors
			α-Glucosidase Inhibitors
			Sodium-Glucose Transporter Inhibitors
			Colesevelam
			Bromocriptine
		Glucose-Lowering Agents Requiring Injection
			Insulins
				Long-Acting Insulins
				Short-Acting Insulins
				Premixed Insulins
				Human Versus Analogue Insulins
			Insulin Delivery Devices
			GLP1 Receptor Agonists
				Short-Acting GLP1 Agonists
				Long-Acting GLP1 Agonists
			Amylin Receptor Agonists
	Practical Aspects of Treatment
		A Team Approach
		Identifying Pathophysiologic Subgroups
			Latent Autoimmune Diabetes of Adulthood
			Pancreatic Diabetes
			Monogenic Diabetes
			Standardized Versus Personalized Tactics
		A Standardized Initial Therapeutic Approach
			Metformin
			Stepwise Combination Therapy
	Considerations in Personalizing Therapy
		Oral Agents and Injected Therapies Other than Insulin
			Basal Insulin
			Treating Postprandial Hyperglycemia
		Examples of Personalized Choices of Therapy
			Minimizing Cardiovascular Risks
			Minimizing Hypoglycemia
			Minimizing Weight Gain
			Minimizing Costs
	Special Situations in Clinical Management
		Severe Hyperglycemia at Diagnosis
		Youth-Onset T2DM
		Pregnancy
	Preventing Type 2 Diabetes Mellitus
	Future Directions
36 - Type 1 Diabetes Mellitus
	Diagnosis
	Animal Models
		Nonobese Diabetic Mouse Model
		Induced Models of T1DM
	Histopathology
		Mechanisms of Beta-Cell Death in T1DM
	Natural History of T1DM—Historical Concepts
		Natural History of T1DM From Long-Term Family and Population Studies
	Genetics
		Overview of Disease Prevalence
		Twin Studies
		The Major Histocompatibility Complex
		Other Loci
		Genetic and Immunologic Heterogeneity by Age of Onset
		Monogenic Forms of Diabetes
			Neonatal Diabetes
			Maturity-Onset Diabetes of the Young
			Autoimmune Polyendocrine Syndrome Type I (AIRE Gene Mutations)
			X-Linked Polyendocrinopathy, Immune Dysfunction, and Diarrhea (Scurfy Gene)
		The Genetic Risk Score
	Environmental Factors
		Models to Explain the Influence of Environment
		Candidate Environmental Factors
			Infection
			Vaccines
			Dietary Factors
	Natural History of T1DM—Emerging Concepts
		Beta-Cell Mass Is Not Equal in All Individuals
		Pancreatic Exocrine Abnormalities in T1DM
		Metabolic Progression Before Hyperglycemia
		C-Peptide Loss After Hyperglycemia
		Transient Hyperglycemia
		Emerging Biomarkers of T1DM Natural History and Diagnosis
		Stages in the Natural History of T1DM
	Immunotherapy for the Prevention and Reversal of T1DM
		Immunosuppression
		Immunologic Vaccination
		Therapeutic Targeting for Mechanisms of Beta-Cell Death
	Pancreas and Islet Cell Transplantation
		Stem Cell or Xenogeneic Islet Cell Transplantation
	Disorders Associated With Immunity to Insulin/Insulin Receptor
		Insulin Autoimmune Syndrome
		Insulin Allergy
		Anti-Insulin Receptor Autoantibodies
	Clinical Presentation
		Laboratory Findings at Presentation
	Treatment
		Principles of T1DM Management
		Glycemic Targets
		Lifestyle Management: Nutrition and Exercise
		Nutrition Therapy
		Physical Activity and Exercise
		Insulin Therapy
			Background
			Insulin Preparations
			Initial Management of Newly Diagnosed T1DM
			Initiation of Insulin Therapy
			Insulin Dose Determination
			Other Insulin Regimen Options
		Blood Glucose Monitoring
		Continuous Glucose Monitoring
		Continuous Subcutaneous Insulin Infusion
		AID: “The Artificial Pancreas”
		Proportional Integral Derivative AID
		Fuzzy Logic AID
		Model Predictive Control AID
		Decision Support Systems
		Use of Adjunctive Drugs in T1DM
			Pramlintide
			Metformin
			Incretin-Based Therapies
			SGTL1 and SGLT2 Inhibitors
		Outcomes Beyond HbA1c
		Transition in Care From Pediatric to Adult Health Care Settings and Beyond
	Acute Diabetic Emergencies
		Diabetic Ketoacidosis
			Pathophysiology of DKA
			Epidemiology and Risk Factors for DKA
			Prevention of DKA /Sick Day Management
				Insulin Dosing During Sick Days
				Prevention/Treatment of Dehydration During Sick Days
				Mini-Dose Glucagon
				Education
			Treatment of DKA
		Other Complications
		Comorbidities
			Thyroid Disease
			Celiac Disease
37 - Complications of Diabetes Mellitus
	Biochemistry and Molecular Cell Biology
		Clinical Overview
		Physiologic Reactive Oxygen Species Production Is Essential for Normal Intracellular Signaling and Cellular Homeostasis
		Mechanisms of Hyperglycemia-Induced Damage
			Increased Aldose Reductase Substrate Conversion
			Increased Intracellular Formation of the Major Advanced Glycation End Products—Precursor Methylglyoxal
			Activation of Protein Kinase C β, δ, and θ
			Increased Protein Modification by O-GlcNAc
			Increased Soluble Epoxide Hydrolase
			Reduced Pyruvate Kinase M2 Activity
			Different Hyperglycemia-Induced Pathogenic Mechanisms Reflect a Single Upstream Process: Mitochondrial Overproduction of ROS
		Insulin Resistance Increases Fatty Acid Oxidation, Causing Mitochondrial Overproduction of ROS
		Diabetes Reduces Activity of Nuclear Erythroid-Related Factor 2, the Master Regulator of Antioxidant Gene Expression
		Diabetes Activates the NLR Family Pyrin Domain Containing 3 Inflammasome
		Diabetes Activates the Transcription Factor NFAT
		Diabetes Increases Neutrophil Extracellular Traps
		Nonresolving Inflammation in Metabolic Syndrome, Diabetes, and Atherosclerosis
		Diabetes Alters Mitochondrial Dynamics
		Genetic Determinants of Susceptibility to Microvascular Complications
		Noncoding RNAs and Diabetic Complications
		Molecular Basis for Metabolic Memory
		Epidemiology and Impact of Proliferative Diabetic Retinopathy and Diabetic Macular Edema
		Pathophysiology of Diabetic Retinopathy
		Clinical Features of Diabetic Retinopathy
			Risk Factors
			Clinical Findings
			Classification Systems
				Classification of Diabetic Retinopathy
				Classification of Diabetic Macular Edema
				International Classification of Diabetic Retinopathy and Diabetic Macular Edema
			Other Ocular Manifestations of Diabetes
		Monitoring and Treatment of Diabetic Retinopathy
			Comprehensive Eye Examination
			Initial Ophthalmic Evaluation
			Follow-Up Ophthalmic Examination
			Evaluation and Treatment of Proliferative Diabetic Retinopathy
				Treatment of Nonproliferative Diabetic Retinopathy
			Treatment of Diabetic Macular Edema
				The pathogenesis of DME is highly complex, and a variable response to treatment modalities has been observed in many patients. I...
			Control of Systemic Disorders and Effect of Systemic Medications
	Diabetic Nephropathy
		Natural History of Nephropathy in Type 1 Diabetes
			Stage 1: Hyperfiltration
			Stage 2: The Silent Stage
			Stage 3: Microalbuminuria
			Stage 4: Macroalbuminuria
			Stage 5: Uremia
		Natural History of Nephropathy in Type 2 Diabetes
		Pathogenesis of Diabetic Nephropathy
		Pathology of Diabetic Renal Disease
		Other Renal Manifestations of Diabetes
			Renal Artery Stenosis
			Renal Papillary Necrosis
			Renal Tubular Acidosis
			Contrast-Induced Nephropathy
		Management of Diabetic Kidney Disease
			Glycemic Control in Diabetic Kidney Disease
			Blood Pressure Control in Diabetic Kidney Disease
		Evaluation of Additional Approaches to the Management of Diabetic Kidney Disease
		Treatment of the Diabetic Uremic Patient
		The Burden of Nephropathy
	Diabetic Neuropathies
		Epidemiology and Impact of Diabetic Neuropathies
		Pathophysiology of Diabetic Neuropathies
		Clinical Features of Diabetic Distal Symmetrical Polyneuropathy
			Clinical Symptoms
			Clinical Signs of Diabetic Neuropathy
			Differential Diagnosis of Diabetic Neuropathy
			Classification of Diabetic DSPN
			Graded Scores for the Classification of DSPN
			Treatment of DSPN
			Disease-Modifying Therapy in DSPN
			Treatment of Painful Neuropathy
		Other Diabetic Somatic Neuropathies: Clinical Features and Treatment Paradigms
		Clinical Features of Diabetic Autonomic Neuropathy
	Diabetic Heart Disease
		Coronary Artery Disease
			Effect of Diabetes on Risk of Coronary Heart Disease (CHD)
			Aggregation of Traditional CHD Risk Factors in Diabetes
			Insulin Resistance, Plasma Glucose, and Excess CHD Risk in Diabetes
		Cardiovascular Disease in Patients With Metabolic Syndrome
			Definitions and Diagnosis
			Cardiovascular Consequences of Metabolic Syndrome
		The Role of Glycemic Control in Improving Cardiovascular Outcomes
		Studies Using Insulin-Sensitizer Medications
		Studies Using Newer Antidiabetic Medications: A New Era?
			Dipeptidyl Peptidase 4 Inhibitors and Cardiovascular Disease
			GLP1RAs and Cardiovascular Disease
			SGLT2 Inhibitors and Cardiovascular Disease
		Characteristic Features and Treatment of Dyslipidemia in Diabetic Patients
		Characteristic Features and Treatment of Hypertension in Diabetic Patients
		Acute Coronary Syndromes in Diabetes Mellitus
		Cardiomyopathy in Patients With Diabetes Mellitus
	The Diabetic Foot
		Epidemiology of Diabetic Foot Ulceration
		Pathogenesis of Foot Ulceration
			Diabetic Neuropathy and the Foot Ulcer
			Callus, Deformity, and High Foot Pressures
			Peripheral Vascular Disease, Diabetic Foot Ulcers, and Amputation Risk
		Prevention of Foot Ulceration and Amputation
		The Diabetic Foot Care Team
		Classification of Foot Ulcers
		Management of Diabetic Foot Ulcers
			Neuropathic Foot Ulcer Without Osteomyelitis (Wagner Grades 1, 2; University of Texas Grades 1a, 1b, 2a, 2b)
			Neuroischemic Ulcers (Wagner Grades 1, 2; University of Texas Grades 1c, 1d)
			Osteomyelitis (Wagner Grade 3; University of Texas Grades 3b, 3d)
			Gangrene (Wagner Grades 4, 5)
		Charcot Neuroarthropathy
		Adjunct Treatments for Foot Ulcers
			Tissue-Engineered Skin and Platelet-Derived Growth Factors
			Negative-Pressure Wound Therapy (NPWT)
			Achilles Tendon Lengthening Procedures
			SGLT2 Inhibitors and Diabetic Foot Disease
38 - Hypoglycemia
	Physiology of Defense Against Hypoglycemia
		Glucose Metabolism
		Systemic Glucose Balance
		Responses to Hypoglycemia
		Clinical Manifestations of Hypoglycemia
		Maintenance of Systemic Glucose Balance
	Clinical Hypoglycemia
		Definition and Diagnosis
		Clinical Classification of Hypoglycemia
	Hypoglycemia in Persons With Diabetes
		The Clinical Problem of Hypoglycemia in Diabetes
			Frequency of Hypoglycemia in Diabetes
			Impact of Hypoglycemia in Diabetes
			Clinical Definition and Classification of Hypoglycemia in Diabetes
		Pathophysiology of Glucose Counterregulation in Diabetes
			Insulin Excess
			Defective Glucose Counterregulation and Hypoglycemia Unawareness
			HAAF in Diabetes
		Risk Factors for Hypoglycemia in Diabetes
			Absolute or Relative Insulin Excess
			Risk Factors for HAAF
		Prevention of Hypoglycemia in Diabetes
			Acknowledge the Problem
			Apply the Principles of Aggressive Glycemic Therapy
			Consider the Conventional Risk Factors
			Consider the Risk Factors for HAAF
		Treatment of Hypoglycemia in Diabetes
	Hypoglycemia in Persons Without Diabetes
		The Decision to Evaluate for Hypoglycemia
		Clinical Classification of Hypoglycemic Disorders
			Ill or Medicated Individual
			Seemingly Well Individual
		Diagnostic Approach
		Treatment of Hypoglycemia Disorders
	Hypoglycemia in Infancy and Childhood
		Intolerance of Fasting
		Hyperinsulinism
		Inborn Errors of Metabolism (Enzyme Deficiencies)
	Acknowledgments
	Disclosures
39 - Neuroendocrine Control of Energy Stores
	The Biologic Control of Energy Balance
		Leptin Signals the Repletion of Adipose Stores
	The Hypothalamic Melanocortin System
	Hypothalamic Systems and Signals That Regulate Energy Balance
		Leptin-Regulated Hypothalamic Circuits
		Roles for NPY/AGRP Neurons in Energy Balance
			Ghrelin
			Roles for the Paraventricular Nucleus in Energy Balance
			Specific Roles of Paraventricular Nucleus Neuronal Subsets in Metabolic Homeostasis
		Role for the Ventromedial Nucleus in Energy Balance
		Serotonergic Control of Energy Balance
		The Role of Insulin and Glucose in the Regulation of Energy Homeostasis
		Estrogen
	Central Nervous System Control of Thermogenesis
	Control of Glucose Homeostasis by the Brain
		Ventromedial Nucleus Control of Glucose and Energy Homeostasis
		POMC Neurons Sense Changes in Glucose Concentration
			Glucose-Inhibited Neurons of the Arcuate Nucleus and Lateral Hypothalamic Area
	Intersection of Energy Balance and Reward Circuits
		The Lateral Hypothalamic Area Links Food Intake Control and Arousal
	Brainstem Circuits That Regulate Energy Balance
		Gut Peptides Involved in Satiety and Hunger
			GLP1 Action in the Central Nervous System
			Peptide YY (PYY)
			Cholecystokinin (CKK)
			Amylin
			GDF15
			Bariatric Surgery
40 - Obesity
	Definition of Obesity
		Body Mass Index
		Body Fat Distribution
	Physiology of Energy Balance
		Central Nervous System Regulation of Appetite
		Signals From the Periphery Regulating Appetite
	Energy Expenditure
		Body Weight Set-Point
	Pathogenesis of Obesity: Genes and Environment
		Environmental Effects in High-Risk Populations
		Influences of Childhood and Parental Obesity
		Genetics and Obesity
			Monogenic Causes of Obesity
				Prohormone Convertase 1 Gene Mutation
				Mutation of the Neurotrophin Receptor TrkB
				Single-Minded Homolog 1 (SIM1) Gene Mutation
				Src Homology 2B 1 (SH2B1) Deficiency
			Obesity Syndromes
				Prader-Willi Syndrome
				Bardet-Biedl Syndrome
			Polygenic Causes of Obesity
	Adipose Tissue as an Endocrine and Immune Organ
		Leptin
		Resistin
		Adiponectin
		Estrogens
		Selected Cytokines
			Tumor Necrosis Factor α
			Interleukin 6
		Brown Adipose Tissue
	Metabolically Normal Obesity
	Adverse Consequences of Obesity
		Obesity as a Disease Risk Factor
			Metabolic Syndrome
			Type 2 Diabetes
			Dyslipidemia
			Hypertension
			Cardiovascular Disease
			Liver Disease
			Obstructive Sleep Apnea
			Musculoskeletal Disease
			Cancer
			Diagnostic and Therapeutic Approach
			Benefits of Intentional Weight Loss
		Dietary Intervention
			Caloric Restriction
			Macronutrient Composition
			Physical Activity
			Behavior Modification
			Pharmacotherapy
		Endoscopic Gastric Therapies
		Bariatric Surgery
41 - Disorders of Lipid Metabolism
	Lipid Biochemistry and Metabolism
		Simple and Complex Lipid Structure
			Fatty Acids
			Triglycerides
			Phospholipids
			Cholesterol
		Fatty Acid Metabolism
			Fatty Acid Biosynthesis
			Fatty Acid Oxidation
		Triglyceride and Phospholipid Metabolism
			Triglyceride Synthesis
			Phospholipid Synthesis
			Lipolysis of Triglyceride Stores in Adipose Tissue
			Lipoprotein Lipase
		Cholesterol Metabolism
			Cholesterol Absorption, Synthesis, and Excretion
				Nuclear Receptors and Lipid Metabolism
				Plasma Lipoproteins, Apolipoproteins, Receptors, and Other Proteins
		Major Lipoproteins
		Major Apolipoproteins
			Apolipoproteins AI, AII, AIV, and AV
			Apolipoprotein B
			Apolipoproteins CI, CII, and CIII
			Apolipoprotein E
		Major Receptors Involved in Lipid Metabolism
			LDL Receptor Gene Family
				LDL Receptor
				LDL Receptor–Related Protein 1
			Pattern Recognition Receptors
				Scavenger Receptors
				Toll-Like Receptors
		Other Enzymes and Transfer Proteins Mediating Lipid Metabolism
			Hepatic Lipase
			Endothelial Lipase
			Proprotein Convertase Subtilisin/Kexin Type 9
			Lipoprotein-Associated Phospholipase A2
			Cholesteryl Ester Transfer Protein
			Lecithin:Cholesterol Acyltransferase
	Integrative Physiology of Lipid Metabolism
		Exogenous Lipid Transport
		Endogenous Lipid Transport
		Reverse Cholesterol Transport and Dysfunctional HDL
	Overview of Hyperlipidemia, Dyslipidemia, and Atherogenesis
	Hypertriglyceridemia
		Fasting Hyperchylomicronemia
		LPL Deficiency
		Postprandial Hyperlipidemia
		Diagnostic Evaluation of Severe Hypertriglyceridemia
			Moderate Fasting Hypertriglyceridemia Due to Elevated VLDL
			Secondary Causes of Hypertriglyceridemia
				Diabetes Mellitus
				Renal Failure
				Drugs
				Diet and Alcohol
		Diagnostic Evaluation of Moderate Hypertriglyceridemia
	Hypercholesterolemia Without Hypertriglyceridemia
		Polygenic Hypercholesterolemia
		Genetic FH
		Familial Defective Apolipoprotein B100
		Rare Mutations Associated With Elevated LDL Levels
		Elevated Plasma Lp(a)
		Lipoprotein(X)
		Sitosterolemia
		Cerebrotendinous Xanthomatosis
		Hypothyroidism and Elevated Cholesterol
		Diagnostic Evaluation of Isolated Hypercholesterolemia
		Increased HDL
			Genetic Disorders Causing Increased HDL
	Elevated Triglycerides and Cholesterol
		Combined Hyperlipidemia
		Familial Dysbetalipoproteinemia
		Hepatic Lipase Deficiency
		Nephrotic Syndrome
		Protease Inhibitor Use in Human Immunodeficiency Virus Infection
		Immunosuppressive Regimens
		Diagnostic Evaluation of Elevated Triglycerides and Cholesterol
	Hypocholesterolemia
		Familial Hypobetalipoproteinemia
		Abetalipoproteinemia
		Chylomicron Retention Syndrome
		Familial Hypoalphalipoproteinemia
			Apolipoprotein AI Mutations
			Lecithin: Cholesterol Acyltransferase Deficiency
			ABCA1 Deficiency
	Treatment of Lipid Disorders
		Evidence Supporting Treatment of Lipid Disorders: Cholesterol and Cardiovascular Disease
		Measurement of Plasma Lipids
		Treatment of High LDL
		Hyperchylomicronemia-Induced Pancreatitis
			Screening for Secondary Disorders
			Patient Selection and Treatment Goals
		Specific Therapies
			Lifestyle Treatment
			Drug Treatment
				HMG-CoA Reductase Inhibitors (Statins)
				Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors
				Ezetimibe
				Bile Acid Sequestrants
				Fibrates
				Omega-3 Fatty Acids
				Niacin
		Combination Therapies
			Combination Therapy for Other Hyperlipidemias
				Statin Plus Fibrate
				Other Combinations
				Treatment for Chylomicronemia Syndrome
				Treatment of FH
				Treatment of Familial Combined Hyperlipidemia
				Treatment of Metabolic Syndrome
				Treatment of Dysbetalipoproteinemia
				Treatment for Elevated Plasma Lp(a)
				Treatment for Low Levels of HDL
		Summary of Treatment of Lipid Disorders
42 - Multiple Endocrine Neoplasia
	Introduction to Multiple Endocrine Neoplasia Syndromes
	MEN Type 1
		Clinical Features and Management
			Parathyroid Tumors
				Clinical Features
				Treatment
			Pancreatic NETs
			Gastrinoma
				Clinical Features
				Treatment
			Insulinoma
				Clinical Features
				Treatment
			Glucagonoma
				Clinical Features
				Treatment
			VIPoma
				Clinical Features
				Treatment
			NF Pancreatic NETs
				Clinical Features
				Treatment
			Somatostatinoma
			GHRHoma
			Pituitary Tumors
				Clinical Features
				Treatment
			Adrenal Tumors
				Clinical Features
				Treatment
			Carcinoid Tumors
				Thymic Carcinoids
				Bronchial Carcinoids
				Gastric Carcinoids
			Other Tumors
				Central Nervous System Tumors
				Lipomas
				Facial Angiofibromas and Collagenomas
				Thyroid Tumors
				Breast Cancer
		Molecular Genetics
			MEN1 Gene
			Germline MEN1 Mutations
			MEN1 Polymorphisms
			MEN1 Phenocopies and Mutations in Other Genes
			Somatic MEN1 Mutations
			Functions of the Menin Protein and Insights Into ­Mechanisms of Tumorigenesis
		Animal Models
			Conventional Men1 Mouse Knockout Models
			Conditional Men1 Mouse Knockout Models
			Nonendocrine Phenotypes in Men1 Mouse Knockout Models
			Preclinical Evaluation of Drug Therapies in Men1 Mouse Models
		Genetic Testing, Tumor Surveillance, and Organization of Care
			Clinical Utility of MEN1 Mutational Analysis
			Surveillance of “At-Risk” Individuals
	MEN Types 2 and 3
		Clinical Features and Management
			Medullary Thyroid Carcinoma
				Clinical Features
				Treatment
			Prophylactic Thyroidectomy in MEN2
			Postoperative Evaluation and Management of Patients With MTC
			Management of Advanced Disease
			Targeted Therapies for MEN2-Associated MTC
			Pheochromocytoma
				Clinical Features
				Treatment
			Primary Hyperparathyroidism
				Clinical Features
				Treatment
			Additional Clinical Features Associated With MEN2A ­Variant Disorders
				Familial MTC-Only
				MEN2 With CLA
				MEN2 With HSCR
			Additional Clinical Manifestations Associated With MEN3
		Molecular Genetics
			The RET Proto-Oncogene
			Germline RET Mutations
			Somatic RET Mutations and Rearrangements
			RET Polymorphisms
			RET Structure and Function
			RET Mutations and Receptor Function
		Animal Models
		Genetic Testing, Tumor Surveillance, and Organization of Care
			Clinical Utility of Genetic Testing for MEN2 and MEN3
			Screening and Intervention in RET Mutation Carriers
	MEN Type 4
		Clinical Features and Management
		Molecular Genetics and Animal Models
		Genetic Testing, Tumor Surveillance, and Organization of Care
	Future Directions and Concluding Remarks
	Acknowledgments
43 - The Immunoendocrinopathy Syndromes
	Autoimmunity Primer
	Natural History of Autoimmune Disorders
		Genetic Associations
		Environmental Triggers
		Development of Organ-Specific Autoimmunity
		Failure of Gland
	Autoimmune Polyendocrine Syndrome Type I
		Clinical Features
		Genetics
		Diagnosis
		Therapy and Follow-Up
	Autoimmune Polyendocrine Syndrome Type II
		Clinical Features
		Diagnosis
		Therapy
	Other Polyendocrine Deficiency Autoimmune Syndromes
		Immunodysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome
		CTLA4, STAT3, and LRBA Mutations
		Anti–Insulin Receptor Autoantibodies
		POEMS Syndrome
		Kearns-Sayre Syndrome
		Thymic Tumors
		Wolfram Syndrome
		Omenn Syndrome
		Chromosomal Disorders
	Conclusion
44 - Endocrinology of HIV/AIDS
	Adrenal Function
		Adrenal Insufficiency
		Glucocorticoid Excess: Adrenal Shunting and Cortisol Resistance
		Medication Effects
		Clinical Assessment
	Gonadal Function
		Male Gonadal Dysfunction
		Female Gonadal Dysfunction
	Thyroid Function
	Fluid Balance and Electrolytes
		Sodium
		Potassium
	Calcium Homeostasis and Bone Changes
		Calcium Homeostasis
		Bone Loss: Prevalence, Etiologic Factors, and Treatment Strategies
		Bone Metabolism in HIV-Infected Children
		Avascular Necrosis of Bone
	The GH/IGF1 Axis
	Glucose Homeostasis and Pancreatic Function
	Metabolic and Body Composition Changes in HIV-Infected Patients
		The AIDS Wasting Syndrome and Loss of Lean Body Mass
		Changes in Fat Mass and Distribution
		Lipid Abnormalities
		Hyperglycemia and Insulin Resistance
		Treatment of Metabolic and Body Composition Changes in HIV-Infected Patients
			Treatment of AIDS Wasting and Loss of Lean Body Mass
			Strategies for Treating Lipoatrophy and Subcutaneous Fat Loss
			Treatments for Visceral Fat Accumulation
			Insulin-Sensitizing Strategies
			Leptin Treatment for Metabolic Dysregulation Among HIV-Infected Patients With Lipoatrophy
			Lipid Management
	CVD in HIV-Infected Patients
		Strategies for Hyperlipidemia Among HIV-Infected Patients
		Anti-Inflammatory Strategies for CVD in HIV
45 - Neuroendocrine Tumors and Related Disorders
	Phylogenesis and Embryology
	Molecular Genetics
	Classification
	Biochemistry
	Clinical Presentation
		The Carcinoid Syndrome
			Flushing
			Diarrhea
			Carcinoid Heart Disease
			Bronchial Constriction
			Other Manifestations of the Carcinoid Syndrome
		Carcinoid Crisis
		Other Clinical Manifestations of Carcinoid Tumors
	Diagnosis
		Histopathologic Diagnosis
		Biochemical Diagnosis
		Localization Procedures
	Treatment
		Somatostatin Analogues
		Interferons
		Chemotherapy
		Other Agents
		Surgery
		Irradiation
	Prognosis
	Other Flushing Disorders
		Medullary Thyroid Carcinoma and VIPoma
		Mastocytosis and Related Disorders
46 - Managing Reproductive Disorders in Cancer
	What Is Oncofertility, and Why Is It Important?
		Scope of the Problem
		Reproductive Health Concerns During Cancer Treatment
			Fertility
			Contraception During Cancer Therapy
			Gonadal Dysfunction
				Women With Cancer
				Men With Cancer
			Physical Changes Related to Cancer Therapy
	Logistics of Fertility Preservation
		Importance of Fertility Preservation and Restoration
		Fertility Loss, Preservation, and Restoration in Female Cancer Patients
			Epidemiology of Cancer in Young Female Patients
			Risks of Gonadotoxicity and Fertility Loss in Young Female Patients
			Fertility Preservation and Restoration Options for Young Female Patients
			Established Options for Fertility Preservation in Women and Girls
				Embryo Freezing
				Egg Freezing
			Debatable Options for Fertility Preservation in Women and Girls
				GnRH Analogues and Hormonal Suppression
				Oophoropexy
				Gonadal Shielding
				Fractionated Chemotherapy and Radiotherapy
			Experimental Options for Fertility Preservation in Women and Girls
				Ovarian Tissue Freezing and Autotransplantation
				IVM of Oocytes
				Artificial Ovary
				Stem Cells
				Neoadjuvant Cytoprotective Pharmacotherapy
		Fertility Loss, Preservation, and Restoration in Male Patients With Cancer
			Epidemiology of Cancer in Young Male Patients
			Risks of Gonadotoxicity and Fertility Loss in Young Male Patients
			Fertility Preservation and Restoration Options in Young Male Patients
			Established Options for Fertility Preservation in Men and Boys
				Sperm Freezing
			Debatable Options for Fertility Preservation in Men and Boys
				GnRH Analogues and Hormonal Suppression
				Gonadal Shielding
				Fractionated Chemotherapy and Radiotherapy
			Experimental Options for Fertility Preservation in Men and Boys
				Testicular Tissue Freezing
				Stem Cells
				Neoadjuvant Cytoprotective Pharmacotherapy
				Other Experimental Options
		Decision-Making Strategies for Young Female and Male Patients With Cancer
	Challenges of Fertility Preservation
		Factors That Prohibit Oncofertility Support
		Special Patient Populations
		Financial and Ethical Considerations
		Methods for Addressing Challenges
			Providing Personalized Risk Assessment
			Practice Management, Knowledge, and Access Barriers to Clinical Care
			Inclusion of Psychological Support Is Critical to Oncofertility Clinical Care Models
			Access and Affordability
			Public Awareness
			Distinguishing Between Oncofertility, Infertility, and Social Egg Freezing
	Summary and Next Steps




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