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
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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
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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
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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
