Endocrine Hypertension: From Basic Science to Clinical Practice

Front Cover
Endocrine Hypertension
Endocrine Hypertension
Copyright
Foreword
Contents
Contributors
Editors' brief resumes
Invited senior authors' profiles
Preface
1 - Endocrine hypertension—an overview
Graphical Abstract
Introduction
Primary hypertension versus secondary hypertension
Individual chapters
Catecholamines and blood pressure regulation
Adrenocortical hormones and BP regulation
Hypothalamic–pituitary–adrenal axis and blood pressure regulation
Renin-angiotensin–aldosterone system and blood pressure regulation
Monogenic hypertension: an overview
Primary aldosteronism (Conn's syndrome)
Familial hyperaldosteronism
Congenital adrenal hyperplasia and hypertension
Endocrine hypertension: discovering the inherited causes
Pheochromocytomas and hypertension
Paragangliomas and hypertension
ACTH-dependent Cushing syndrome
Adrenal Cushing's syndrome
Hypertension in growth hormone excess (acromegaly) and deficiency
Hypertension in thyroid disease and hyperparathyroidism
Obesity, insulin resistance, and obstructive sleep apnea
Endocrine hypertension in children
Endocrine hypertension in pregnant woman
Imaging for patients with endocrine hypertension
Systematic approach for the diagnosis and management of endocrine hypertension
Recent trends/emerging concepts
Genetic testing for familial PPGL
Genetic testing for familial hyperparathyroidism
Genetic testing for familial hyperaldosteronism especially GRA
Conclusions
References
2 - Catecholamines and blood pressure regulation
Graphical Abstract
Introduction
Catecholamines and autonomic physiology
The synthesis, storage, and regulation of catecholamines
Metabolism of catecholamines
Adrenoceptors, subtypes, and associated second messenger systems
Neuroendocrine effects of catecholamines on blood pressure
Metabolic regulation by catecholamines
Biologic effects
Summarizing the net effect of catecholamines on vascular hemodynamics
PPGLs and excess catecholamine states
Deleterious cardiac effects of excess catecholamines: CICMP
Stress cardiomyopathy: impaired adrenoceptor and second messenger signaling
Hypertrophic cardiomyopathy: load-dependent and nonload-dependent remodeling
Dilated cardiomyopathy: cardiotoxic effects of catecholamines
Deleterious vascular effects of catecholamines
Catecholamines and alterations in renal physiology
Catecholamines and other organs
Catecholamines and autonomic failure
Summary and conclusions
Learning points
References
3 - Adrenal cortical hormones and blood pressure regulation
Graphical Abstract
Introduction
Physiological aspects
An overview of adrenal steroid synthetic pathways
Regulation of steroidogenesis: cholesterol, StAR, and p450scc
Aldosterone synthesis in the zona glomerulosa
Cortisol synthesis in the zona fasciculata
Adrenal androgen synthesis and regulation in the zona reticularis
Glucocorticoids, receptors, and cardiovascular system effects
The glucocorticoid receptor (GR)
Glucocorticoid receptor and blood pressure regulation
Mineralocorticoids, receptors, and effects on the cardiovascular system
The mineralocorticoid receptor
MR and blood pressure regulation: genomic effects
MR and blood pressure: non-genomic actions
Androgens, receptors, and cardiovascular system effects
Pathophysiological alterations in adrenocortical hormones and effects on cardiovascular homeostasis
Glucocorticoid excess states (including non-neoplastic Cushing's)
Mineralocorticoid excess states: primary aldosteronism (PA) and familial hyperaldosteronism
Apparent mineralocorticoid excess
Androgen deficiency/excess states (including congenital disorders such as CAH)
Androgen deficiency and blood pressure
Androgen excess and blood pressure
Emerging research questions
Summary and conclusions
Learning points
References
4 - Hypothalamic–pituitary–adrenal axis and blood pressure regulation
Graphical Abstract
Introduction
Physiology of blood pressure regulation and HPA axis
POMC (pro-opiomelanocortin): its role in metabolism and energy balance
CRH (corticotropin-releasing hormone) and AVP (arginine vasopressin) control the expression of POMC (pro-opiomelanocortin)
Pathophysiology of hypertension and HPA axis
HPA axis and autonomic nervous system (in relation to BP)
HPA axis, adrenal hormones, and blood pressure
HPA axis and metabolic syndrome
HPA axis, various hormonal disorders, and hypertension
Summary and conclusions
Learning points
References
5 - Renin–angiotensin–aldosterone system and blood pressure regulation
Graphical Abstract
Introduction
Physiological aspects of RAAS
RAAS, inflammation, and remodeling
RAAS blocking agents and cardiovascular protection in hypertension
ACE inhibitors
ARBs
Direct renin inhibitors
Dual RAAS inhibition
ACEI versus ARBs
Mineralocorticoid receptor antagonists
Conclusions
Learning points
References
6 - Monogenic hypertension: an overview
Graphical Abstract
Introduction
Genetics of monogenic hypertension
Monogenic hypertension with hypokalemic alkalosis, low renin, and raised aldosterone
Monogenic hypertension with hypokalemic alkalosis, low renin, and reduced aldosterone
Monogenic hypertension with hyperkalemic acidosis, low renin, and variable aldosterone
Monogenic hypertension with normokalemia and normal renin and aldosterone levels
Summary
Learning points
References
7 - Primary aldosteronism (Conn's syndrome)
Graphical Abstract
Introduction
The renin–angiotensin–aldosterone system
Who should be screened? (The epidemiology of primary aldosteronism)
Aldosterone–renin ratio as screening test
Confirmatory test after positive ARR
Subtyping in primary aldosteronism: adrenal vein sampling or imaging?
Laparoscopic surgery and peri-operative management
Medical therapy of primary aldosteronism
Familial forms of primary aldosteronism
Conclusions
Learning points
References
8 - Familial hyperaldosteronism
Graphical Abstract
Introduction
Pathophysiology of familial hyperaldosteronism
Subtypes of familial hyperaldosteronism
Familial hyperaldosteronism type 1
Familial hyperaldosteronism type 2
Familial hyperaldosteronism type 3
Familial hyperaldosteronism type 4
PASNA syndrome
Emerging research questions/future research
Summary and conclusions
Learning points
References
9 - Congenital adrenal hyperplasia and hypertension
Graphical Abstract
Introduction
Genetics of CAH (in general—all forms)
Pathophysiology of hypertension in CAH
11β-hydroxylase deficiency
Clinical presentations
Diagnostic approach for 11β-hydroxylase deficiency
Management algorithm
Therapeutic targets
17α-hydroxylase deficiency
Clinical presentation
Diagnostic approach
Management algorithm
Therapeutic targets
Overtreatment of CAH
When to suspect of CAH in patients with hypertension
Future research
Summary and conclusions
Learning points
References
10 - Endocrine hypertension: discovering the inherited causes
Graphical Abstract
Introduction
Inherited disorders of endocrine hypertension
Monogenic hypertension associated with suppressed PAC and PRA
Liddle syndrome
Epidemiology
Pathophysiology
Genetics
Clinical features
Investigations
Management
Congenital adrenal hyperplasia (CAH)
Epidemiology
Pathophysiology
Genetics
Clinical features
Investigation
Management
Apparent mineralocorticoid excess (AME)
Epidemiology
Pathophysiology
Genetics
Clinical features
Investigation
Management
Geller syndrome
Epidemiology
Pathophysiology
Genetics
Clinical features
Investigation
Management
Monogenic hypertension associated with normal PAC and low PRA
Pseudohypoaldosteronism type II (Gordon syndrome)
Epidemiology
Pathophysiology
Genetics
Clinical features
Investigation
Management
Monogenic hypertension associated with high PAC and low PRA
Familial hyperaldosteronism type 1 (FH-1) or glucocorticoid suppressible aldosteronism
Epidemiology
Pathophysiology
Genetics
Clinical features
Investigation
Management
Familial hyperaldosteronism type 2 (FH-2)
Epidemiology
Pathophysiology
Genetics
Clinical features and investigation
Management
Familial hyperaldosteronism type 3 (FH-3)
Epidemiology
Pathophysiology
Genetics
Investigation
Clinical features
Management
Familial hyperaldosteronism type 4 (FH-4)
Monogenic hypertension associated with elevated PAC and PRA
Renin-secreting juxtaglomerular cell tumors (JGCT)
Epidemiology
Genetics
Pathophysiology
Clinical features
Investigations
Management
Monogenic hypertension associated with normal PAC and PRA
Familial pheochromocytoma and paragangliomas
Epidemiology
Genetics and pathophysiology
Clinical features
Investigation
Management
Primary generalized glucocorticoid resistance (Chrousos syndrome)
Epidemiology
Pathophysiology
Genetics
Clinical features
Investigation
Management
Carney complex
Epidemiology
Pathophysiology
Genetics
Clinical features
Investigation
Management
Summary and conclusions
Learning points
References
11 - Pheochromocytomas and hypertension
Graphical Abstract
Introduction
Molecular and genetic aspects of PCCs
Tumor clusters
Clinical and biochemical characteristics of PCC: genotype-phenotype correlations
Pathophysiology
Metastatic risk
Clinical presentation
Diagnostic workup
Biochemical testing
Diagnostic imaging
Anatomical imaging
Functional imaging
MEN2 and VHL PCCs
Molecular diagnosis
Management
Presurgical and surgical management of PCC
Locoregional approaches
External beam radiotherapy
Other approaches
Systemic therapy
Chemotherapy
Radionuclide therapy
Tyrosine kinase inhibitors (TKIs)
Other agents
Follow-up
Areas of uncertainty/emerging concepts
Summary and conclusions
Learning points
References
12 - Paragangliomas and hypertension
Graphical Abstract
Introduction
Epidemiology of paragangliomas and hypertension
Pathophysiology of paraganglioma and hypertension
Genetics of paragangliomas
Clinical presentation
Biochemical investigations
Anatomical and functional imaging studies
Perioperative medical management of paragangliomas
Surgery for management of paragangliomas
Curative surgery
Metastatic paragangliomas
Palliative surgery
Systemic therapy
Chemotherapy
Radionuclide therapy
Local ablative therapy
Follow-up care of patients with paragangliomas
Management in special populations
Children
Pregnancy
Elderly
Areas of uncertainty/emerging research
Summary and conclusions
Learning points
References
13 - ACTH-dependent Cushing's syndrome
Graphical Abstract
Introduction
Clinical presentation, screening, and diagnosis of Cushing's syndrome
Localization testing: distinguishing between ACTH-dependent and ACTH-independent Cushing's syndrome
Epidemiology of hypertension in Cushing's syndrome
Pathophysiology of hypertension in Cushing's syndrome
Other complications of Cushing's syndrome
Treatment of Cushing's syndrome and associated hypertension
Antihypertensive therapy in Cushing's syndrome
Role of medical therapy for CS in the treatment of hypertension
Adrenal steroidogenesis inhibitors
Pituitary targeted agents
Glucocorticoid receptor blockers
Follow up of Cushing syndrome and hypertension
Summary
Learning points
References
14 - Adrenal Cushing's syndrome
Graphical Abstract
Introduction
Causes and epidemiology of adrenal Cushing syndrome
Genetic syndromes associated with adrenal Cushing syndrome
Genetics of ACTH -independent Cushing syndrome
Clinical features
Pathophysiology of hypertension in adrenal Cushing syndrome
Investigations for adrenal CS
Treatment of adrenal CS
Preoperative treatment of adrenal CS
Postoperative treatment of adrenal CS
Long-term outcome of adrenal CS
Autonomous cortisol secretion in adrenal incidentaloma
Areas of uncertainty/emerging concepts
Summary and conclusions
Learning points
References
15 - Hypertension in growth hormone excess and deficiency
Graphical Abstract
GH and IGF-1 physiological effects
GH and IGF-1 in the blood vessels
The role of GH and IGF-1 in the myocardium
The role of GH and IGF-1 in the kidney
Acromegaly and hypertension
Epidemiology
Pathophysiology of hypertension in acromegaly
Plasma volume expansion
Sodium-retaining effect and the role of ENaC in acromegaly
Overview of other possible mechanisms for enhanced fluid retention in acromegaly
Increased peripheral vascular resistance
Vascular remodeling of the resistance arteries
Endothelial dysfunction
Impaired glucose metabolism
Sleep apnea syndrome
Hypertension phenotype and cardiovascular comorbidities
Characteristics of acromegaly related hypertension
Acromegaly and comorbidities
Cardiomyopathy
Valvulopathy
Arrhythmias
Diabetes mellitus
Hyperlipidemia
Atherosclerosis and mortality
Screening for acromegaly in hypertensive patients
When to suspect acromegaly in hypertensive patients
Treatment
Therapeutical options in acromegaly
The effect of disease activity on blood pressure
Hypertension management
Growth hormone deficiency and hypertension
Epidemiology
Pathophysiology of hypertension in AGHD
Endothelial dysfunction
Increased sympathetic activity
Vitamin D deficiency
Insulin resistance
Phenotype of AGHD and characteristics of blood pressure profile
AGHD and comorbidities
Cardiac structure and performance
Obesity
Metabolic syndrome
Lipids
Impaired glucose metabolism
Atherosclerosis and mortality
Screening for AGHD
When to suspect AGHD in hypertension?
AGHD diagnosis
Treatment
Impact of AGHD management on blood pressure
Summary and closing remarks
Learning points
References
16 - Hypertension in thyroid disease and primary hyperparathyroidism
Graphical Abstract
Introduction
Thyroid disease
Physiology of hypothalamo–pituitary–thyroid axis and cardiovascular system
Pathophysiology of hypertension in thyroid dysfunction
Subclinical or overt hypothyroidism and associated hypertension
Epidemiology
Clinical features
Investigation and management
Impact of treatment of hypothyroidism on hypertension and cardiovascular disease
Subclinical or overt hyperthyroidism and associated hypertension
Epidemiology
Clinical features
Investigation and management
Impact of treatment of hyperthyroidism on hypertension and cardiovascular disease
When to suspect hypothyroidism and hyperthyroidism in hypertensive subjects?
Parathyroid disease
Physiology of parathyroid hormone action
Pathophysiology of hypertension in primary hyperparathyroidism
Bidirectional relation between renin–angiotensin–aldosterone system and PTH
Epidemiology of PHPT
Clinical features of primary hyperparathyroidism
Investigation and management
Impact of parathyroidectomy in hypertension and cardiovascular disease
When to suspect PHPT in hypertensive subjects?
Summary and conclusions
Learning points
References
17 - Obesity, insulin resistance, and obstructive sleep apnea
Graphical Abstract
Introduction
Epidemiology of OSA
OSA and obesity
Diagnosis of OSA
Pathophysiology of OSA-related secondary hypertension
Nocturnal sympathetic overdrive
Chronic inflammation and oxidative stress driven by hypoxia
Nocturnal fluid shifts
Cardiac effects of nocturnal negative intrathoracic pressure
Activation of the RAAS
OSA and insulin resistance
Management of OSA
Conservative management
CPAP
Oral appliances
Surgical management
Weight loss therapies
Conclusions
Learning points
Acknowledgments
References
18 - Endocrine hypertension in children
Graphical Abstract
Introduction
Primary versus secondary hypertension in children
Endocrine hypertension in children
Clinical presentation of endocrine hypertension in children
Catecholamine producing tumors
Pheochromocytomas and paragangliomas in children
Diagnosis
Cushing's syndrome in children
Diagnostic evaluations
Biochemical phenotype of mineralocorticoid excess in children
Primary aldosteronism
Glucocorticoid-remediable aldosteronism (GRA)
Primary generalized glucocorticoid resistance (Chrousos syndrome)
Apparent mineralocorticoid excess (AME)
Liddle syndrome
Pseudohypoaldosteronism type II (Gordon syndrome)
Geller syndrome
Congenital adrenal hyperplasia and hypertension in children
Excessive growth hormone production
Thyroid and parathyroid disorders and hypertension in children
Obesity, insulin resistance, and obstructive sleep apnea (OSA) associated with hypertension in children
Diagnostic approach to endocrine hypertension in children
Management of endocrine hypertension in children
Summary and conclusions
Learning points
References
19 - Endocrine hypertension in pregnancy
Graphical Abstract
Introduction
Primary hyperaldosteronism in pregnancy
Cushing syndrome in pregnancy
Pheochromocytoma and paraganglioma (PPGL) in pregnancy
Primary hyperparathyroidism
Hyperthyroidism and hypothyroidism in pregnancy
Acromegaly in pregnancy
Rare causes of endocrine hypertension in pregnancy
Adrenal cortical carcinoma/deoxycorticosterone-secreting adrenal tumor
Liddle’s syndrome
Hypopituitarism
Familial hyperaldosteronism
Geller syndrome
Summary and conclusions
Learning points
References
Further reading
20 - Imaging for patients with endocrine hypertension
Graphical Abstract
Introduction
Adrenal computed tomography (CT)
Adrenal magnetic resonance imaging (MRI)
Adrenal venous sampling (AVS)
Imaging for mineralocorticoid excess states
Imaging for glucocorticoid excess states
Positron-emission tomography (PET)/CT to localize an ectopic source of ACTH secretion
Imaging for catecholamine excess states
Imaging for primary hyperparathyroidism
Neck ultrasound
4D computed tomography (CT)
SPECT/CT imaging with 99mTc-sestamibi
PET/CT with 18-fluorine labeled choline analogues
Imaging for hyperthyroidism and hypothyroidism
Thyroid ultrasound
Planar scintigraphy
Imaging for acromegaly and AGHD
MRI of the pituitary
Summary and conclusions
Learning points
References
21 - Systematic approach to the diagnosis and management of endocrine hypertension
Graphical Abstract
Introduction
Primary aldosteronism (PA)
Clinical diagnosis
Symptoms and signs of PA
The importance of accurate assays in the diagnostic workup of PA
Screening for PA
Confirmatory testing for PA
Subtype differentiation
To whom should AVS be offered and how should it be performed?
Management
Surgical management
Medical management
Other mineralocorticoid forms of hypertension
11β-hydroxylase deficiency
Clinical diagnosis
Management
17α-hydroxylase deficiency
Clinical diagnosis
Management
Primary glucocorticoid resistance (PGR) or Chrousos syndrome
Clinical diagnosis
Management
Syndrome of apparent mineralocorticoid excess (SAME)
Clinical diagnosis
Management
DOC-secreting tumors
Clinical diagnosis
Management
Ectopic ACTH syndrome
Clinical diagnosis
Management
Activating mutations of the MR or Geller syndrome
Clinical diagnosis and management
Liddle syndrome
Clinical diagnosis
Management
Familial hyperkalemic hypertension (Gordon syndrome)
Clinical diagnosis
Management
Pheochromocytoma and paraganglioma
Prevalence, pathophysiology and clinical presentation
Diagnosis
Management
Surgical management
Perioperative management
Follow-up
Cushing's syndrome
Prevalence, pathophysiology and clinical presentation
Diagnosis
Management
Surgical management
Pharmacological management
Multimodal treatment
Acromegaly
Prevalence, pathophysiology, and clinical presentation
Diagnosis
Management
Thyroid disorders
Hypothyroidism
Prevalence, pathophysiology, and clinical presentation
Diagnosis
Management
Hyperthyroidism
Prevalence, pathophysiology, and clinical presentation
Diagnosis
Management
Primary hyperparathyroidism
Prevalence, pathophysiology, and clinical presentation
Diagnosis
Management
Renal artery stenosis and other rare forms of renin driven hypertension
Clinical presentation
Diagnostic approach
Management
Page kidney
Reninoma
Conclusion
Learning points
References
Index
A
B
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D
E
F
G
H
I
J
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M
N
O
P
R
S
T
U
V
W
X
Z
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