Endocrinology of Aging

Front-Matter_2021_Endocrinology-of-Aging
	Front matter
Copyright_2021_Endocrinology-of-Aging
	Copyright
Contributors_2021_Endocrinology-of-Aging
	Contributors
Preface_2021_Endocrinology-of-Aging
	Preface
Acknowledgments_2021_Endocrinology-of-Aging
	Acknowledgments
Chapter-1---Basic-Principles-of-the-Aging-Process-with-Endoc_2021_Endocrinol
	BASIC PRINCIPLES OF THE AGING PROCESS WITH ENDOCRINE AND NUTRITIONAL IMPLICATIONS, AGING AND DISEASE IN ENDOCR ...
		Introduction
			What Is Aging?
			Senescent Cells and Senolysis
		Basic Principles of the Aging Process With Endocrine and Nutritional Implication
		Growth Velocity as Determinant of Lifespan Potential
		Nutritional Influence on the Rate of Aging
		Wear and Regulation: Two Mechanisms That Determine the Aging Process
			Importance of Endocrine System
			Wear Regulation. Its Importance for the Course of Aging
		Problems and Risks of Hormonal Treatment of the Aging Process
		The Fallacy of Hormonal ``Replacement´´ as ``Antiaging Medicine´´
		Aging and Disease in Endocrinology
		Summary of Physiological Aging and Endocrine system
		Endocrinopathies in Advanced Age. Characteristics and Considerations for Diagnosis and Therapy
		SELECTED REFERENCES
		Further Fundamental Reading
			Senescent Cells And Senolysis
			Basic Principles of the Aging Process with Endocrine and Nutritional Implication
			Aging and Disease in Endocrinology
Chapter-2---Physiology-and-Diseases-of-the-Hypothalamic-_2021_Endocrinology-
	Physiology and Diseases of the Hypothalamic-Pituitary Axis in the Elderly
		Chapter Outline
		Hypothalamic-Pituitary Axis and Aging
		Changes of Prolactin With Age
		Changes of GH and IGF-1 With AGE
		Possible Mechanisms
		Pituitary Diseases in the Elderly
			Pituitary Tumors
				Prevalence and Anatomical Pathology
				Clinical Presentation at Diagnosis
				Pituitary Apoplexy
		Treatment1717Fleseriu M et al. Hormonal replacement in hypopituitarism in adults: an Endocrine Society clinical practice guide
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				Neuroradiologic Diagnosis
				Neuroradiological Stages
				Functional Diagnostic Features of Hypopituitarism (see Chapters 10, 11: Male Hypogonadism in Advanced Age)
		Water Deprivation: Interpretation
		Arginine-Vasopressine Test
		Interpretation
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				Hypopituitarism. Functional Diagnosis: Endocrine Society Practice Guidelines, 201617
		Central hypothyroidism (CH)
		Hyperprolactinemia
		Central adrenal insufficiency (AI)17
		GH deficiency
		Central hypogonadism in men
		Central hypogonadism in women2323In premenopausal women, determine estradiol (E2) and serum FSH/LH, if there is oligomenorrhea
		Central DI
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				Pituitary Incidentaloma: Endocrine Society Clinical Practice Guidelines, 2011
		Incidentaloma Evaluation and Recommendations for Surgery2525Freda P et al. Pituitary incidentaloma Endocrine Society guideline
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				Transsphenoidal Surgery
			Secretory Pituitary Tumors
				Acromegaly
		Prognosis
		Causes of Death
		Complications30,3535Pivonello R et al. Pituitary 20: 46-62, 2017.
		Functional Diagnosis
		Transsphenoidal Surgery
		Medical Treatment
		Somatostatin Analogs
		Long-Acting Somatostatin Analogues: Formulations
		Long-Acting Somatostatin Analogues: Adverse Events
		Pegvisomant
		Cabergoline
		Evaluation Postsurgical
		ACOMEGALY FOLLOW UP
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				Prolactinoma
					Diagnosis
					Hyperprolactinemia
						Diagnostic algorithm
						Hyperprolactinemia caused by drugs
						Hyperprolactinemia due to disinhibition of PRL secretion
					Specifics of Therapy in Older Patients
					Treatment With Dopaminergic Agonists
		Microprolactinomas: Indication and Progression
		Macroprolactinomas: Indication and Progression
		Discontinuation of DA
		Microprolactinomas
		Macroprolactinomas
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					Treatment of Nontumoral Hyperprolactinemia
		Idiopathic Hyperprolactinemia
		Antipsychotic Drugs
		Renal Insufficiency in Terminal Stages
		Primary Hypothyroidism
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					Diagnosis & Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline48
				ACTH Secreting Adenomas
			Pituitary Tumors. Radiotherapy
		Hypopituitarism: Treatment
			Hypocortisolism
			Central Hypothyroidism
			GH Replacement Therapy
		Arguments in Favor6,5959Kokshoorn NE et al. Eur J Endocrinol 164: 657-665, 2011.,6060Snyder PJ. Growth hormone deficienc
		Arguments Against6,13,59,60,6161Filipsson H, Johannsson G. Eur J Endocrinol 161: S85-S95, 2009.,6262Veldhuis JD. Nat Rev
			Replacement With Sex Steroids: Testosterone Replacement Therapy in Men
		In men: Testosterone Replacement Therapy (TRT)
		TRT: Contraindications
		TRT: Formulations and monitoring2,13,20,64,8585Snyder PJ. Approach to older men with low testosterone. Uptodate. 2020.
			Central Diabetes Insipidus
		Endocrine Society clinical practice guideline (2016)17
			Drugs and Replacement Doses
		Endocrine Society clinical practice guideline (2016)17
		Selected References
		Further Fundamental Reading
			Hypothalamus-Hypophysis in Advanced Age
				Hypothalamic-Pituitary Axis and Aging
				Pituitary Tumors
				Secretory Pituitary Tumors
				Hypopituitarism: Treatment
Chapter-3---Physiology-and-Diseases-of-the-Parathyroid-_2021_Endocrinology-o
	Physiology and Diseases of the Parathyroid Glands in the Elderly
		Chapter Outline
		Parathyroid Glands in the Elderly
			Changes in Calciotropic Hormones and Calcium Balance in the Elderly
			Physiological Changes of the Bone Composition in the Elderly
		Hypoparathyroidism and Hypocalcemia in the Elderly
			Introduction
			Differential Pathogenic Diagnosis of Hypocalcemia
			Symptoms and Signs of Hypocalcemia
		Neuromuscular
		Dermatologic
		Cardiac
		Psychiatric
		Ocular
		Other
			Diagnosis
		Laboratory Tests
			Acute Hypocalcemia: Treatment
			Chronic Treatment
				Goals9
				Chronic Treatment With Calcium and Calcitriol
		Follow-Up9
		Limitations and Side Effects of Calcium and Calcitriol Replacement
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				Chronic Replacement With Recombinant Human Parathyroid Hormone
		Indications1818Authorized use in any etiology of hypoparathyroidism except in autosomal-dominant hypocalcemia types 1 and 2,
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				Magnesium Supplementation. Hypomagnesemia Treatment
		Hypercalcemia in the Elderly
			Clinical Presentation
			Diagnosis
			Differential Diagnosis
		Primary Hyperparathyroidism in the Elderly
			Considerations
			Summary of Recommended Diagnostic Tests
			Localization
			Surgery
				General Considerations
				Rationale
				Surgical Benefits in the Elderly
				PHPT Criteria for Surgical Indication44
		To Be Performed by an Expert Parathyroid Surgeon
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				Surgical Approaches and Indications
					Images on Surgical Approaches and Indications
		Indications of a MIP30,36,45
		Advantages of the MIP30,36,45,68
		Disadvantages of MIP
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				Parathyroidectomy: Complications
				Postoperative Follow-Up
					Hungry Bone Syndrome
					Cure, Recurrence, and Persistence
					Postoperative Normocalcemic Elevation of PTH After Curative Parathyroidectomy
			Medical Follow-Up in Nonsurgical Patients35,44
		Monitoring in nonsurgical patients35,37,44
			Medical Treatment in Nonsurgical Patients
		Drugs to Minimize Bone Mass Loss35,37,116116Shakaran S et al. J Clin Endocrinol Metab 95: 1653-1662, 2010.,117117Marcocc
		Drugs to Normalize Calcium Level: Cinacalcet35,117,119119Cinacalcet. Summary of product characteristics.www.ema.europa.eu/docs
			Normocalcemic Primary Hyperparathyroidism
		Selected References: Parathyroid And Age–HP
		FURTHER FUNDAMENTAL READING
		Parathyroid and age. Hypoparathyroidism
		Hyperparathyroidism
Chapter-4---Vitamin-D-and-Calcium-Deficiency-in-the_2021_Endocrinology-of-Ag
	Vitamin D and Calcium Deficiency in the Elderly
		Chapter Outline
		Synthesis, Metabolism, and Effects of Vitamin D
		Vitamin D Sources
		Vitamin D and Metabolites: Pharmacological Differences
		Secondary Hyperparathyroidism in the Elderly
		Prevalence of Vitamin D Deficiency in the Elderly
		Causes of Vitamin D Deficiency
		Pathogenic Mechanisms of Vitamin D Deficiency
		Optimal Vitamin D Concentrations
		Deficiency of Vitamin D in the Elderly. Clinical Manifestations7
		Vitamin D Deficiency and Muscle Function
		Physiologic Basis
		Extraskeletal Actions of Vitamin D
		Vitamin D Deficiency, Depression, and Cognitive Status
		Vitamin D Deficiency and Mortality Risk
		Vitamin D Deficiency Screening With 25(OH)D
		Evaluation of Vitamin D Deficiency in the Elderly
		Prevention of Vitamin D Deficiency in the Elderly
		Vitamin D Requirements: Preventive Doses8,10,15,35,36,63,6464Ish-Shalom S et al. J Clin Endocrinol Metab 93: 3430-3435,
		Prevention of Calcium Deficiency in the Elderly
		Calcium and Vitamin D Supplementation in Osteoporosis
		Vitamin D Deficiency in the Elderly: Treatment
			First Line Therapy
		The required cholecalciferol (D3)7474Cholecalciferol 25,000 I.U. Oral solution. doses are highly variable depending on:
			Insufficiency of Vitamin D
			Deficiency of Vitamin D
			Controversy About Dosage
			Monitoring and Safety10,16,63
			Calcidiol
			Calcitriol63
		Selected Bibliographic References
		Further Fundamental Reading
Chapter-5---Senile-and-Postmenopausal-Osteoporosis--Patho_2021_Endocrinology
	Senile and Postmenopausal Osteoporosis: Pathophysiology, Diagnosis, and Treatment
		Introduction
			Skeleton Compartments
			Composition of Bone Mineral Matrix
			Physiologic Bone Modeling and Remodeling
		Senile Osteoporosis
			Definitions
			Differential Characteristics
			Development as an Expression of Bone Aging
		Bone Changes With Aging
			Cortical and Trabecular Bone Loss With Aging According to Sex
		Bone Loss and Aging in Men
		Age-Related Changes of GH and Testosterone on Bone Heath
		Mechanisms of Aging Bone Loss
			Oxidative Stress
			Oxidative Stress and Cytokines1,8,19
			Increased Adipogenesis and Decreased Osteogenesis
			Calcium and Vitamin D
		Pathogenic Role of GH/IGF/IGFBPS in Osteoporosis
		Bone Loss During Menopause
			Pathogenesis of Postmenopausal Osteoporosis
		Effects of Estrogen on the Bone Cells
		Estrogen Deficiency Summary
		Epidemiology of Osteoporosis and Fractures
		Risk Factors for Osteoporosis
			Genetic Factors8
			Exercise19,44
			Bone Cells Respond to Mechanical Stimuli
			Calcium Intake
			Vitamin D and PTH
			Tobacco
			Alcohol
		Diagnosis of Osteoporosis
			Clinical diagnosis
			Osteoporosis Diagnostic Tools
			Dual Energy X-Ray Absorptiometry
			WHO Osteoporosis Classification
			Trabecular Bone Score
			Vertebral Fracture Assessment
			Bone Turnover Markers
			Fracture Risk Assessment
		Senile Osteoporosis and Glucocorticoids
		Effects on Bone Cells
			Prevalence and Clinical Relevance
			Diagnosis
			Assessing Fracture Risk Using FRAX
			Prevention and Treatment
			Indications for Pharmacological Treatment
		Senile Osteoporosis and Obesity
		Senile Osteoporosis and Diabetes Mellitus
			Treatment
		Senile Osteoporosis and Sarcopenia
		Treatment of Osteoporosis in the Elderly
			Whom to Treat. Recommendations
			Physical Exercise
			Calcium and Vitamin D
			Prevention of Falls67
		Pharmacological Intervention in Osteoporosis
			Introduction
			Bisphosphonates General Concepts
			Alendronate
			Alendronate Studies
			Risedronate
			Risedronate Studies
			Zoledronic Acid
			Zoledronic Acid Studies
			Denosumab
			Denosumab Studies
			Teriparatide
			Teriparatide Studies
			Abaloparatide
			Abaloparatide Studies
			Romosozumab
				Romosozumab Studies
		Efficacy of Treatments for Postmenopausal Osteoporosis
		Combination or Sequential Therapy
		Treatment Monitoring
		Drug Holiday
		Atypical Femur Fracture
		Osteonecrosis of the Jaw
		Selected References
		Further Fundamental Reading
Chapter-6---Physiology-and-Diseases-of-the-Thyroid-Gland-in-_2021_Endocrinol
	Physiology and Diseases of the Thyroid Gland in the Elderly: Physiological Changes, Hypothyroidism, and Hypert ...
		Chapter Outline
		Thyroid Changes With Aging
			Introduction
			Thyroid Function Modifications
				Thyrotropin (TSH)
				Thyroxine (T4)
				Triiodothyronine (T3)
		Primary Hypothyroidism in the Elderly
			Special Clinical Characteristics
			Epidemiology
			Etiology
			Effects of Drugs on the Thyroid
			Clinical Manifestations
				Symptoms
				Signs
			Laboratory Diagnosis
		ATA/AACE 2012 Adult Hypothyroidism Guidelines2222Garber JR et al. Clinical practice guidelines for hypothyroidism in adults:
			Diagnosis: Other Complementary Tests
		Hypothyroidism in the Elderly: Treatment
			American Thyroid Association 2014 Guidelines
			Sodium Levothyroxine Treatment
			Special Considerations
			Parameters to Consider in Optimizing Therapy
		Central Hypothyroidism in the Elderly: Differentiation from Primary Hypothyroidism
		Hypothyroidism in the Elderly: Myxedema Coma
		Subclinical Hypothyroidism in the Elderly
			Diagnostic Criteria
			Causes41
			Clinical Relevance
				CV disease or mortality
				Other cardiac evaluation parameters and CV risk factors
			Treatment With Levothyroxine
				Effects of L-Thyroxine (LT4) Replacement Therapy
		Hypothyroidism Screening
		Hyperthyroidism in the Elderly
			Prevalence and Etiology
			Hyperfunctioning Multinodular Goiter: Etiopathogenesis
			Differentiating Clinical Manifestations
			Diagnostic Characteristics
			Hyperfunctioning Multinodular Goiter: Diagnosis74
			Graves' Disease: Diagnosis74
			Hyperfunctioning Thyroid Nodule (Toxic Adenoma): Diagnosis
			Subacute Thyroiditis
				Clinical Stages: Presentation Is Tri-Phasic
				Diagnosis
			Treatment
				Thionamides
					Monitoring
					Side effects
				Beta Blockers74
				Radioiodine Therapy74
				Surgery81
				Types
					Subtotal Thyroidectomy
					Total Thyroidectomy (C)
		Subclinical Hyperthyroidism in the Elderly
			Definition and Prevalence
			Etiology
			Natural History
			Diagnostic Criteria74,89
			Risks
			Treatment Recommendations74,88,89
		Appendices
		Selected References
		Further Fundamental Reading
			Hypothyroidism
			Hyperthyroidism in the Elderly
Chapter-7---Physiology-and-Diseases-of-the-Thyroid-Gland-in_2021_Endocrinolo
	Physiology and Diseases of the Thyroid Gland in the Elderly: Thyroid Nodules, and Simple Goiter
		Chapter Outline
		Thyroid Nodules in the Elderly
			Epidemiology
			Diagnosis and Treatment: Considerations
			Initial Diagnostic Algorithm3,5,9
			The 2017 Bethesda System for Reporting Thyroid Cytopathology: Recommended Diagnostic Categories
			Clinical Management and Malignity Risk of the Bethesda System in Each Diagnostic Category5
			Molecular Markers in FNA Aspirate: Fundamentals
			FNA Aspirate and Panels for Diagnostic Use
			Other Markers for Malignancy
			Indeterminate Thyroid Nodules: Diagnostic Decisions
		IMAGES OF THYROID NODULES
		Simple (Nontoxic) Goiter in the Elderly
			Simple Goiter Concept and Etiology
			Anatomical-Clinical Correlation
			Epidemiology
			Pathogenesis
			Clinical Manifestations
			Diagnosis
			Intrathoracic or Substernal Goiter
				Considerations on the Thyroid Growth
				Physical Examination
				Complementary Tests
				Images of Intrathoracic Goiters
			Treatment
				Considerations
				Surgery
				Radioiodine
				Treatment With Radioiodine After rhTSH
				Safety of Radioiodine Treatment24,31
				TSH Suppression Therapy With L-T4
		Suppressive thyroxine dosage
		APPENDICES
			Thyroid Ultrasound Report Format
			Nontoxic Multinodular Goiter And Benign Normal-functioning Thyroid Nodule. Follow-up Recommendations5,24,31
			Thyroid Volume. Normal Values
		Selected References
		Further Fundamental Reading
			Thyroid Nodules
			Simple Goiter
Chapter-8---Physiology-and-Diseases-of-the-Thyroid-Gland_2021_Endocrinology-
	Physiology and Diseases of the Thyroid Gland in the Elderly: Thyroid Cancer
		Thyroid Cancer in the Elderly
			Epidemiology
			Pathological Anatomy
		Differentiated Thyroid Cancer (DTC)
			Particulars of Treatment in the Elderly
			DTC Treatment
				Preoperative Staging
				DTC Treatment Directed to the Thyroid
		Proper Surgical Terminology is Recommended23
		Surgical Recommendations18,27
		Hemithyroidectomy18,23
		Total/Near Total Thyroidectomy18,23
		Head and neck lymphatic drainage
			Lymphadenectomy
				Lymphatic Involvement in DTC
				Types of Lymphadenectomy
				Therapeutic Lymphadenectomy-Central and Lateral
				Prophylactic Central Neck Dissection
		Risk factors to be considered to perform a prophylactic central neck dissection23,42
			Sentinel Lymph Nodes
			Biological Markers
		BRAFV600E
		TERTC228T/C250T
		RAS
			Prophylactic Lateral Lymphadenectomy
			Images of DTC Recurrences and Lymphadenectomy
			Clinicopathologic Staging
			Dynamic Risk Stratification (ATA 2015)
			Staging Based on Mortality Risk
		Risk Stages: European Thyroid Association (2006)
			Influence of Age on Prognosis
			Prognostic Factors
			Radioiodine
				Objectives and Considerations
				Preparation
				Consensus for Postoperative I-131 Ablation or Treatment
			Serum thyroglobulin: Diagnostic value and recommendations
			Follow-Up
				Low-risk DTC algorithm with negative anti-thyroglobulin antibodies
				Algorithm for posoperative radioiodine administration. Initial management
				Criteria for Disease-Free Remission
			TSH suppression with levothyroxine
			Management of Suspected Recurrent or Metastatic Disease
			Recurrent or Metastatic Disease Management
		Chemotherapy
			Differentiated Thyroid Cancers Images
			Papillary Microcarcinoma in the Elderly
		Factors Increasing the Risk of Progression
		Experience With Active Surveillance13,118,1191,120
			Follicular Thyroid Cancer in the Elderly Particularities
		Medullary Thyroid Cancer in Advanced Age
			Peculiarities in Advanced Age
			Clinicopathologic Tumor Staging
			Diagnosis
				Initial Evaluation125,129
				Serum Calcitonin. Diagnostic value
			Treatment: Focus on Thyroid And Lymph Nodes
			Residual Disease: Persistently High Calcitonin129
			Images of The Medullary Thyroid Cancer
		Anaplastic Thyroid Cancer (ATC)
			Diagnosis
			Gene Mutations in Anaplastic Thyroid Cancer and Therapy
		Thyroid Lymphoma
			General Considerations
			Presentation and Diagnosis
			Treatment
			Prognosis
		Selected References
		Further Fundamental Reading
			Differentiated Thyroid Cancer
			Papillary Microcarcinoma
			Medullary Thyroid Cancer
			Anaplastic Thyroid Cancer
			Thyroid Lymphoma
Chapter-9---Physiology-and-Diseases-of-the-Adrenal-Gla_2021_Endocrinology-of
	Physiology and Diseases of the Adrenal Glands in the Elderly
		Chapter Outline
		Physiological Age-Related Changes
			Adrenal Function in Advanced Age (Diagram)
			Hypothalamic-Pituitary-Adrenal Axis Changes With Aging: Possible Clinical Implications
			Changes in Adrenocortical Function With Aging
			Changes in Adrenomedullary Function With Aging
			Acute Stress and the Adrenal Medulla2
		Primary Adrenal Insufficiency in Advanced Age
			Etiology
			Clinical Manifestations
			Diagnostic Algorithm
			Functional Diagnosis
			Etiologic Diagnosis
		CT scan of adrenal glands
			Treatment
			Adrenal Crisis
		Preventive Measures: GC Adjustments5
		Identification/Awareness of the Condition
		Education of Patients and Relatives
		Adrenal Incidentaloma in Advanced Age
			Definition, Prevalence, Evaluation of Malignancy, and Functional Evaluation
			Evaluation and Monitoring
			Radiologic Diagnosis
			Radiological Features of Adrenal Cancer (AC) and Adrenal Metastasis (AM)
			Management
			Follow-Up
		Hypercortisolism in Advanced Age
			Cushings Syndrome
			Aging and Accuracy of Diagnostic Tests
			Subclinical Cushings Syndrome
			Consequences of glucocorticoid treatment in the Elderly
		Adrenocortical Carcinoma
			Overview and Tumor Staging
			Diagnostic Work-Up
			Imaging and Pathology
			Treatment6,7
				Mitotane Adjuvant Therapy
		Mineralocorticoid Excess
		Primary Hyperaldosteronism in Advanced Age
			Prevalence and Etiology
			Clinical Manifestations
			Diagnosis
			Algorithm for Management
			Differential Diagnosis of Arterial Hypertension and Hypokalemia
			Treatment
		Pheochromocytoma in Advanced Age
			Prevalence
			Clinical Presentation and Diagnosis
			Biochemical Diagnosis
			Imaging Diagnosis
			Principles of Treatment
			Pathology
		Adrenalectomy
			Minimally Invasive Techniques: Main principles
			Surgical Techniques
			Laparoscopic Transabdominal Approach
			Robotic-Assisted Adrenalectomy
			Single-Access Retroperitoneoscopic Adrenalectomy
			Surgical Pieces of Excised Adrenal Masses by Laparoscopic Surgery
			Partial Adrenalectomy
		Selected References
		Further Fundamental Reading
			Adrenocortical Function and Aging
			Adrenal Insufficiency
			Adrenal Incidentaloma
			Hypercortisolism
			Adrenocortical Carcinoma
			Primary Hyperaldosteronism
			Pheocromocytoma
			Adrenal Laparoscopic Surgery
			Partial Adrenalectomy
Chapter-10---Male-Hypogonadism-in-Advanced-Age--Physiology--_2021_Endocrinol
	Male Hypogonadism in ADVANCED Age: Physiology, Etiology, Diagnosis, and Functional Hypogonadism in the Elderly
		Chapter Outline
		Summary of Testosterone Physiology
		Hypothalamic-Pituitary-Testicular Axis, Changes With Aging
		Testicular Function and Male Hypogonadism in Advanced Age. Andropause
			Total T and Free T Index According to Age in 890 Men in the BLSA
			Linear Segments Per Decade. Longitudinal Effect of Aging on the Adjusted Results of Total T and Free T Index
			Percentage of Healthy Men With Hypogonadism Criteria by Decade of Life in the BLSA
		Male Hypogonadism in Advanced Age. General Concepts
			Definition6,25,26
			Causes
			Symptoms and Signs of Androgen Deficiency
		Late Onset or Functional Hypogonadism
			Prevalence
			Clinical Characteristics
			Interactions With Body Composition, Obesity, and the Metabolic Syndrome
			Interactions With Type 2 Diabetes
			Association With Other Comorbidities
			Association among Serum T Levels, Cardiovascular Events, and Mortality
		Effects of T Treatment in Advanced Age
			Preliminary Studies
			T Trials Study
				Design
				Results I
		T treatment for 1year in older men with low serum T:
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				Results II
		T treatment for 1year in older men with low serum T
		Adverse Effects70,76
		Conclusions70,76
			The Testosterone Effects on Atherosclerosis in Aging Men (TEAAM) Study
				Progression of Coronary CIMT
				Progression of CAC
				Lean Body Mass and Muscle Function Testing
				Fitness Measured as VO2, Work Rate, and Heart Rate
				Summary of TEAAM Results
		In elderly men treated for 36months with transdermal T to physiological levels of total plasma T vs age-matched men given pl
		Diagnosis
			Challenges for Defining and Confirming Diagnosis
			Initial Test: Total T6,21,25
			Conditions with Frequent Occurrence of Low Serum T
		Hypogonadism Due to Klinefelters Syndrome Characteristics in Advanced Age
		Treatment of Functional Hypogonadism
			Treatment Basis6,25
			Therapeutic Measures
				Weight Loss6,25
				Exercise
				Optimization of Chronic Disease Control6,25
				HIV Infection and Male Hypogonadism in Advanced Age
			Specific Treatment of Erectile Dysfunction
			Specific Treatment of Osteoporosis (See Chapter 5: Osteoporosis)
		Selected References
		Further Fundamental Reading
Chapter-11---Male-Hypogonadism-in-Advanced-Age--Therapeutic-Cons_2021_Endocr
	Male Hypogonadism in Advanced Age (Therapeutic Considerations), Gynecomastia in Advanced Age, Benign Prostati ...
		Chapter Outline
		Male Hypogonadism in Advanced Age: Treatment
			Testosterone Treatment
				Basis of Replacement/Treatment1
				Principles
				Main Testoterone Formulations
		T Implants
		T Esters
		Transdermal Route99Arver S et al. Andrology 6: 396-407, 2018.
		Buccal, Bioadhesive T Tablets
		Nasal T Gel
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				Principal Undesirable Effects1,2,3
				Contraindications
				Monitoring1
				Other Potential Adverse Effects
			Testosterone Treatment in Advanced Age and Cardiovascular Risk
				Studies Without Evidence of Increased CV Events in Older Men Treated With T
				Meta-Analysis of T Treatment and Cardiovascular Risk
				Favorable Effects of T Administration on Cardiac Function in Older Men
				Subclinical Atherosclerosis in Older Men Treated With T
			Messages to be Remembered
		Gynecomastia in Advanced Age. Characteristics
			Definition and Etiopathogenesis
			Prevalence
			Diagnostic Laboratory Evaluation
			Laboratory Evaluation. Measure HCG, LH, T, E2
			Therapeutic Management
		Benign Prostatic Hypertrophy and Prostate Cancer: Endocrinological Aspects of Development and Treatment
			Benign Prostatic Hypertrophy and Prostate Cancer: Introduction
			Benign Prostatic Hypertrophy: Pathogenesis and Therapeutic Considerations
				The Following are Pathogenic Areas Under Investigation
				Treatment Considerations of BPH
			Prostate Cancer
			Advanced Age and Prostate Cancer
				Pathogenesis and Therapeutic Considerations
				Hormonal Treatment
		Selected References
		Further Fundamental Reading
			Male Hypogonadism in the Advanced Age: Treatment
			Gynecomastia in Advanced Age
			Benign Prostatic Hypertrophy and Prostatic Cancer
Chapter-12---Menopause-as-a-Manifestation-of-Agin_2021_Endocrinology-of-Agin
	Menopause as a Manifestation of Aging
		Chapter Outline
		Transection of Menopause With Aging
			``Somatic´´ Aging
			Reproductive Aging
		The Menopause Transition
			Early and Late Transition
		Stages of Female Ovarian Function
			Reproductive, Menopause Transition, Menopause/Postmenopause
		Cardiovascular Aging Process
		Reproductive Cardiovascular Aging
			Ovarian Hormone-Mediated
		Aging and Hormone Trials
			Women's Health Initiative (WHI)
			Heart and Estrogen/Progestin Replacement Study (HERS)
		HERS Trial Design1515Huley S et al. JAMA 1280: 605-613, 1998.
			Kronos Early Estrogen Prevention Study (KEEPS)
		KEEPS Trial Design
			Early Versus Late Intervention Trial With Estradiol (ELITE Study)
		ELITE Trial Design1818Hodis HN et al. N Engl J Med 374: 1221-1231, 2016.
			Conclusion
		Metabolism Aging Process
		Reproductive Metabolic Aging
			Is BMI a Valid Measure of Obesity in Postmenopausal Women?
		Bone Aging Process
		Reproductive Bone Aging
			Ovarian Hormone-Mediated
		Sex Steroid Hormones and Bone Mineral Density Over the Menopause Transition
		Reproductive Genitourinary and Libido Aging
		Genitourinary
		Libido
		Neurocircuitry of Desire: Malfunctioning of Reward Pathways
		Prevalence of Female Sexual Problems Associated With Distress and Determinants of Treatment Seeking (Preside)
		Reproductive Brain Aging
			Hot Flashes
			Mood
			Cognition
		Hormonal Therapies
			Effectiveness and Safety
		Effectiveness
		Safety
			Estrogen Only Derivatives
			Estrogen+Progestin Derivatives
			Genitourinary Symptoms of Menopause
		Nonhormonal Therapies
			For Those in Whom Hormonal Therapy is Contraindicated
		Nonpharmacologic Therapies
			Have Yet to Show Significant Benefit in Large Clinical Trials
		Selected references
		Further Fundamental Reading
Chapter-13---Endocrine-Surgery-in-Elderly-Patient_2021_Endocrinology-of-Agin
	Endocrine Surgery in Elderly Patients
		Chapter Outline
		General Concepts
		Alteration of Physiological Functions With Aging
			Overview
			Cardiovascular System
				Morphological Changes
				Functional Changes
				Usefulness of Perioperative Beta-Blockers in Patients at Risk of Cardiac Risk
			Respiratory System
			Renal Function
			Relationship Between Body Composition and Renal Function
			Lower Urinary Tract
			Hepatobiliar Function
			Immune Function
			Homeostasis of Glucose
		Preoperative Assessment
			Overview
			Comorbidities
			Functional Status
			Nutritional Status
			Cognitive Status
		Management of Frequent Use Drugs in the Medical Period of the Elderly
		Endocrine Surgery in the Elderly
			General Principles for Thyroid Surgery
			General Principles for Parathyroid Surgery
			General Principles for Adrenal Surgery
			General Principles for Pituitary Surgery
		Selected References
		Further Fundamental Reading
Chapter-14---Body-Composition-and-Metabolic-Changes-_2021_Endocrinology-of-A
	Body Composition and Metabolic Changes With Aging
		Chapter Outline
		Assessment of Body Composition in Adults
			General Considerations
			Clinical Utility
			Body Compartmentalization
		Both simplistic and advanced methods for body composition analysis exist and are based on the methods by which the body is par
			Anthropometric Measurements
			Research Methods
			MRI
				Ultrasonography
		Changes in Body Composition With Aging
			Lean Body Mass and Fat Mass
			Central Obesity: Pathophysiological Consequences
			Sarcopenia
			Summary of the Standards for DXA, CT, MRI, and US for the Detection of Metabolic Dysfunction in the Elderly
			Relationships Among Body Composition, Hormones, and CV Changes With Age
			Hormonal Interventions-GH/IGF-I, T, DHEA
		Metabolic Changes From Adulthood to Old Age
			Summary
			Metabolic Changes. Biochemical MarkersKanters SD et al. Diabetes Care 24: 323-327, 2001.Procollagen III PeptideThe amino-te ...
				Procollagen III Peptide
				Plasma cAMP
				Glomerular Filtration Rate
				Serum Albumin
		Aging Changes of Glucose Homeostasis and Insulin Regulation
			General Principles
			Changes in Blood Glucose
			Changes in Insulin, C-Peptide, and Glucagon
		Effects of Aging on Insulin Resistance
			Hepatic Production and Muscle Utilization of Glucose
			Age-Related Cellular Mechanisms of Insulin Resistance
			Genetic and Environmental Factors
			Factors Contributing to Age-Related Insulin Resistance23,25,28,29
				Summary
				Lifestyle Changes: Diet Composition and Exercise
				Brown Adipose Tissue24,29
		Effects of Comorbidities and Medications on Insulin Sensitivity and Secretion in the Elderly
		Effects of Aging on Insulin Resistance, Insulin Sensitivity, and Longevity
		Interactions Between Insulin Secretion and Insulin Resistance in Aging
		Effects of Aging on Insulin Secretion. Secretory Insulin Defect
		Pathophysiological defects in type 2 diabetes mellitus
		Selected References
		Further Fundamental Reading
Chapter-15---Obesity--A-Condition-That-Mimics-Premat_2021_Endocrinology-of-A
	Obesity, A Condition That Mimics Premature Aging
		Chapter Outline
		Introduction
		Obesity Prevalence Worldwide
		Overweight/Obesity Incidence Trends in World Regions
		Obesity Prevalence Peaks in Older Population
		Modulatory Factors Affecting the Caloric Balance
		Pathogenic Mechanisms of Obesity
		Acquired, Behavioral Causes of Obesity
		Dietary Patterns that Contribute to Obesity
		Major Co-morbidities in Obesity
		Obesity: Pathophysiologic Definition
		Types of Fat Distribution in Obesity
		Anthropometric Methods to Evaluate Obesity
		Obesity and Morbi-Mortality
		Pathogenic Role of Visceral Obesity in the Metabolic Syndrome
		Common Molecular Mechanisms in Obesity and Aging
			Cellular and Molecular Hallmarks of Aging
			Common Mechanisms Linking Obesity to Aging
			Diabesity and Vascular Aging
			Adipokines Can Directly Contribute to Vascular Aging1,2
		Obesity in the Elderly: Leading Questions
			Body Composition and Energy Metabolism in Aging
			Sarcopenic Obesity
			Obesity Paradox: Myth or Reality?
		Weight Loss Treatment in Elderly
			Benefits of Losing Weight in Older Adults
			Cautions in Losing Weight in Older Adults
			Lifestyle Modifications (Diet and Physical Exercise)
			Pharmacotherapy of Obesity
		Available pharmacotherapy for obesity
			Bariatric Surgery
				Main Contemporary Procedures
					Sleeve (Tubular) Gastrectomy
					Biliopancreatic Diversion (BPD)
					Roux-en-Y Gastric Bypass
		Conclusions
		Selected References
		Further Fundamental Reading
Chapter-16---Relationships-Among-Frailty--Sarcopenia-and-the-E_2021_Endocrin
	Relationships Among Frailty, Sarcopenia and the Endocrine-Metabolic Changes of Advanced Age: Pathophysiology, Prevention, Diagnosis, and Treatment
		Chapter Outline
		Introduction
		Frailty: Definition
		Frailty: Epidemiology
		Frailty: Consequences
		Frailty: Multimorbidity and Dependency
		Pathophysiology of Frailty
			Muscle System: Sarcopenia
				Mechanisms
		Specific mechanisms underlying sarcopenia are not completely clear and are currently under investigation. They can be classif
			Outline placeholder
				Alteration in Muscle Structure and Function
				Aging-Induced Muscle Structure and Function
				Muscle Stem Cells
				Chronic Inflammation
				Oxidative Stress
		Increased production of reactive oxygen species (ROS) or reactive nitrogen species
		Decreased capacity of antioxidant system defense
		Oxidative Stress, Mitochondrial Dysfunction
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				Chronic Inflammation and Oxidative Stress
			Cardiovascular System
			Sarcopenia and Frailty: Interaction With Metabolic and Hormonal Changes
			Hormonal Systems Summary
			Endocrine System
				GH and IGF-I
				Testosterone
				DHEA/DHEAS
				Cortisol
				Vitamin D
			Contribution of Chronic Diseases
			Summary
		Frailty: Clinical Management
			Manifestations
			Prevention
			Diagnosis
				Diagnosis Is a Two-Step Process
			Frailty and Sarcopenia
				Sarcopenia. Diagnosis
			Treatment
			Future Perspectives for Treatment
		Components to Be Adopted by Healthcare Systems to Manage Frailty
		Selected References
		Further Fundamental Reading
Chapter-17---Diabetes-Mellitus-in-the-Elderly_2021_Endocrinology-of-Aging
	Diabetes Mellitus in the Elderly
		Chapter Outline
		Epidemiology of Diabetes in Older Adults
		Prevalence of diabetes mellitus by the year 2030 by world regions:
		Duration of Diabetes
		Consequences of Diabetes in the Elderly
		DM doubles the risk of functional deterioration, especially in frail elderly and noncontrol older patients:
		Characteristics of Diabetes in the Advanced Age Pathophysiology, Clinical Presentation, Diagnosis, and Treatment
			Pathophysiology of Hyperglycemia: Summary
			Difficulty in Diagnosis and Treatment
			Recommendations for Diagnosis
			Clinical Presentation2
			Particulars in Treatment
		Assessment of Elderly Patients With Diabetes
			Care Approach of the Elderly With Diabetes
			Objectives of the Geriatric Integral Assessment
			Integral Functional Evaluation
				Overall Health
			Clinical Assessment and Care
			Comorbidities and Nutritional Status
			Cognitive Impairment
			Dementia
			Cognitive Status: Dementia and Glycemic Control
			Emotional Assessment: Depression2
			Frailty and Sarcopenia1,2
			Cardiovascular Risk Assessment
		Treatment of Hyperglycemia in Older Adults
			Pretreatment Considerations
			Quality of Life and General Objectives
			Expected Benefits of Glycemic Control
			Specific Objectives of Glycemic Control1,8
			Individualized Treatment Plan
			Risk of Hypoglycemia
				Importance of Avoiding Hypoglycemia
				Clinical Spectrum1,8
			Glucose Monitoring
		Glycemic Control Monitoring: HbA1c1,8
		Capillary Blood Glucose Monitoring1,8
			Targets for Glycemia and CV Risk Factors
			Lifestyle Intervention Diet and Exercise1,2,8
			Pharmacologic Treatment
				General Principles1,7,8,14
				Drug Effects, Limitations, and Safety1,8
				Treatment of Type 2 Diabetes in Older Adults, Algorithm
				Drug Therapy
					Metformin
					Sulfonylureas
					Glinides (Repaglinide)
					Tiazolindiones (Pioglitazone)
					Glucosidase Inhibitors (Acarbose, Miglitol)
					DPP-4 Inhibitors
					iDPP-4 Approved Indications
					GLP-1 Receptor Agonists
					SGLT2 Inhibitors
					Insulin Therapy
		Managing Complications in Older Adults With Diabetes
			Introduction
			Macrovascular Disease
				Prevention of CV Complications
				Treatment of Arterial Hypertension
			Microvascular Disease
				Eye Complications1,8
				Chronic Kidney Disease (CKD)
				CKD Classification Based Upon GFR and Albuminuria
				Diabetic Neuropathy
				Diabetic Foot18
			Patients with Diabetes Mellitus and Liver Dysfunction
		Diabetes Education in Older Adults
		Selected references
		Further fundamental reading
Chapter-18---Diabetes-Mellitus-as-a-Risk-Factor-for_2021_Endocrinology-of-Ag
	Diabetes Mellitus as a Risk Factor for Aging
		Chapter Outline
		Diabetes Mellitus Is Associated With Premature Aging
		Higher Prevalence of Diabetes Mellitus With Age
			Global Diabetes Trend From 1980 to 2014
				751 Population Studies With 4.4 million Participants
			The Global Prevalence of DM in Older Adults Will Increase Over the Next 25years
		Diabetes Mellitus Complications Increase With AgeData from: Lipska KJ et al. JAMA Intern Med volume 174: 1116-1124, 2014.Un ...
		Pathophysiology of Type 2 Diabetes
		Pathophysiological Particularities of Diabetes Mellitus in Older Adults
		Impaired Beta-Cell Function in Human Aging
			Insulin Secretion Defects in Advanced Age
		Insulin Resistance in Human Aging
		Insulin Secretion and Resistance in the Advanced Age: Summary
		Comorbidities Affecting Insulin Sensitivity and Secretion in Older Adults7,9,18
		Manifestations of Premature Aging of Diabetes Mellitus
			Diabetes Is a Proaging State30
			Cardiovascular
			Mechanisms of Cardiovascular Aging
			Cognitive Function
			Microangiopathy
			Other Processes28,30,31
		Mechanisms of Premature Aging of Diabetes
			Consequences of Aging According to Specific Phenotypes
			Potential Mechanisms of Premature Aging in Diabetes Mellitus
			Telomere Shortening
			Cellular Senescence Contribution
		Aging as a Therapeutic Target in Diabetes Mellitus
			The Geroscience Hypothesis
			Senescence-Associated Secretory Phenotype (SASP)29,35
			Metformin as a Tool to Target Aging
				Metformin Targets Multiple Pathways of Aging
				Effects on Macrobiota
				TAME (Target Aging with Metformin) Trial38
		New Model of Dysglycemia-Based Chronic Disease
		Selected References
		Further Fundamental Reading
Chapter-19---Dyslipidemia-in-the-Elderly_2021_Endocrinology-of-Aging
	Dyslipidemia in the Elderly
		Chapter Outline
		Lipids and lipoproteins physiology
			Digestion, absorption and Homeostasis
				Cholesterol: Digestion and Absorption
		Absorption Features
			Outline placeholder
				Cholesterol Homeostasis
			Lipoproteins
			Lipid Metabolism: Exogenous and Endogenous Pathways
			HDL Metabolism
			Atherosclerosis: Phases and Risk Factors
			Dyslipidemia: Definition
			Changes of Total and LDL-Cholesterol With Age
		Dyslipidemia. Association with coronary risk
			Principles
			Major Risk Factors of Atherosclerotic Cardiovascular Disease (ASCVD)
			Cholesterol
			ASCVD Risk Categories and LDL-C Treatment Goals
		Dyslipidemia. Association with ASCVD risk
			Oxidized LDL-C and Atherosclerosis
			LDL-C: Particle Size
			HDL Cholesterol
				HDL-C: Independent Prognostic Factor for CAD Risk
			Triglycerides
			Lipid Triad
		Hyperlipidemia
			Fredrikson Phenotypic Classification
			Diagnosis
				History
			Clinical Manifestations
			Secondary Hyperlipidemia: Causes
			Cardiovascular Risk Estimation in the Elderly
		Dyslipidemia in the Elderly
			Basic Principles33,34
			Burden of ASCVD33,34
			Dyslipidemia in The Elderly and ASCVD Risk
		Treatment of dyslipidemia in the elderly
			Why Treat? Summary
			Treatment Approach: Outline
			Diet Treatment14
			Drugs for Hypercholesterolemia: Summary
			Drug Treatment of Dyslipidemia in the Elderly: Statins
				Efficacy in the Elderly
				Basic Pharmacology and Dosage48,49
				Dosage
				For Primary and Secondary Prevention. Initial Statements and Clinical Trials
		Initial Statements33,34
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				Clinical Trials
				Statins and secondary prevention
				Statins and primary prevention
				Cholesterol: The Lower the Better58,59
				Safety: Statin induced-myopathy and other side effects
		Therapy Approach
		Other Side Effects
			Outline placeholder
				Outline placeholder
					Risk of  Transaminases According to Increasing Dosage
			Dyslipidemias in the Elderly Without Diabetes
				Who to Treat?
				ASCVD Prevention
				Secondary Prevention34
				Primary Prevention
				Intensity of Statin Therapy
				Summary of Primary Prevention in the Elderly
			ASCVD Prevention in Older Adults With Diabetes
		Prevention of Cardiovascular (CV) Complications6767Standards of Medical Care-2020 American Diabetes Association. Older adult
			Drugs That Act on Cholesterol Absorption
				Ionic Exchange Resins48
				Ezetimibe
			PCSK9 Inhibitors (Alirocumab and Evolocumab)
			Fibrates48,49
			Treatment of TG/HDL-C Disorders
				HDL Cholesterol: Nonpharmacological Measures
			Hypertriglyceridemia
				Non-pharmacological Measures
				New Guidelines
				Pharmacological Measures
				Marine Omega-3 Fatty Acids. Eicosapentaenoic Acid
				Drug Combinations
		Selected References
		Further Fundamental Reading
Chapter-20---Assessment-of-Nutritional-Status-in-the-Elderl_2021_Endocrinolo
	Assessment of Nutritional Status in the Elderly, Causes and Management of Malnutrition in the Elderly
		Chapter Outline
		Introduction
			Noncommunicable Diseases Risk Factors
		Fruit and vegetable consumption
			Major Causes of Death in the Elderly
			Quality of Life Factors in Aging
		Age-related changes
			Physiological Changes
			Pathological Changes
			Anorexia
			Changes in Gut Microbiome
		Specific Nutritional Needs in the Elderly
			Micronutrients/Vitamins and Minerals
				Vitamins
				Minerals
			Energy Requirement
			Nutrient Needs Change with Aging
		Assessment of Nutritional Status
			Anthropometric Assessment
				Standard Indices
				Alternative Indicators
				Body Composition
			Biochemical/Laboratory Assessment
			Clinical Assessment
			Clinical Signs of Nutritional Deficiencies10
			Comprehensive Geriatric Assessment
			Dietary Assessment
			Model of Nutrition in the Elderly
		Undernutrition or Malnutrition
			Definition
			Global Nutrition Report 2018 WHO
			Risk Factors and Causes of Malnutrition in the Elderly
			Polypharmacy: A Specific Risk and Cause of Malnutrition in the Elderly
			Drug-Nutrient Interactions in the Elderly
			Diagnostic Criteria
			Malnutrition Screening Tools
			Malnutrition and Prognosis of Mortality Risks
			Malnutrition and ICD
			Malnutrition. Consequences in the Elderly
			Malnutrition: Cachexia12
			Malnutrition: Failure to Thrive (FTT)
			Malnutrition: Management in the Elderly
			Treatment of Malnutrition in the Elderly
				Symptom Management
				Issues to Consider
			Adequate Nutrition
			Prevention of Malnutrition in the Elderly
				Food Variety
				Nutrient Density
				Phytochemical Density
		Overnutrition in the Elderly
		Selected References
		Further Fundamental Reading
Index_2021_Endocrinology-of-Aging
	Index