Endocrine Hypertension: From Basic Science to Clinical Practice

412 Pages·2022·12.453 MB·English

by  Joseph M. Pappachan, Cornelius James Fernandez

Endocrine Hypertension
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Endocrine Hypertension
From Basic Science to Clinical Practice
Edited by
Joseph M. Pappachan
Department of Endocrinology & Metabolism, Royal Preston Hospital, The Lancashire Teaching
Hospitals NHS Foundation Trust, Preston, United Kingdom; The University of Manchester,
Manchester, United Kingdom; Faculty of Science, Manchester Metropolitan University, Manchester,
United Kingdom
Cornelius J. Fernandez
Department of Endocrinology & Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS
Trust, Boston, United Kingdom
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Foreword
Endocrinecausesofhypertensionareamongthemostfrequentcausesofsecondaryhypertension,andwiththerecognition
of the increased prevalence of primary aldosteronism, could represent a sizable percentage, perhaps up to 20% of the
aetiologiesofhypertension.Accuratediagnosisoftheseconditionsiscriticalbecauseofthecomplicationsassociatedwith
thepersistenceofdiseaseincasesinwhichdiagnosisisnotmade,andbecausemanyoftheseconditionsmaybecured,in
contrasttoprimaryhypertension,whichcanbecontrolledbutnotcuredinpresenttimes.Thereareguidelinesfordiagnosis
andtreatmentofendocrinehypertensionfrommanyorganizations,suchasthoseoftheEndocrineSocietyoftheUSA,the
2017 AHA/ACC Guideline, and the latest European Guidelines, both for the management of hypertension in general but
includingrecommendationsforendocrine hypertension,andmany othersourcesofrecommendationsthatincludehowto
diagnose and manage endocrine hypertension. However, there is a need for a treatise on endocrine hypertension that
addresses in-depth the etiology, pathophysiology and the molecular underpinnings, the differential diagnosis, and the
management of endocrine hypertension, including the more practical aspects of treatment and follow-up.
EndocrineHypertension,fromBasicSciencetoClinicalPractice,editedbyJosephM.PappachanandCorneliusJames
Fernandezdoespreciselythat.WithXchapterswrittenbyauthoritiesinthefield,EndocrineHypertensionprovidesanin-
depthdescriptionofallaspectsofhypertensionwithendocrineconnotations.Fromadrenalhyperplasiatoacromegaly,and
fromparagangliomasandpheochromocytomatoCushing’s,throughhyperaldosteronisminitsdifferenttypestotheroleof
therenin-angiotensinsystem andthemany forms of monogenic hypertension, noaspect of endocrinehypertension isleft
unexamined. The genetics, molecular and cellular aspects, etiopathogenesis, pathophysiology, clinical description,
screening, and diagnosis, and finally management and follow-up including practical tips, all are addressed in clear and
readableprosethatmakesitnotonlyattractiveandentertainingbutalsohugelyeasytoincorporateintoeverydaypractice.
Chapters on catecholamines and the renin-angiotensin system are followed by ones on pheochromocytoma, para-
gangliomas and different forms of adrenal hypertension, including recent findings on aldosterone-producing cell clusters
and somatic mutations in genes encoding for ion channels and ATPases found in aldosteronomas and aldosterone-
producing cell clusters, and all the genetic, cellular, and molecular heterogeneity in adrenals with an aldosterone-
producing adenoma, including the familial forms of primary aldosteronism.
RarerformsofendocrinehypertensionsuchasacromegalyandCushing’ssyndrome,aswellasthemonogenicformsof
hypertension, require high clinical suspicion butit isimportantthat they bediagnosed. The same appliesto thenotionof
the high frequency of primary aldosteronism, which requires testing in most cases of hypertension because it often has
moresubtlemanifestationsthantheclassicalConn’ssyndrome,anditsdiagnosisandtreatmentcanbeextremelygratifying
and beneficial to patients, with prevention of target organ damage and complications.
Anyone interested in hypertension, from genetics to pathophysiology and molecular and cellular manifestations to
diagnosis and treatment should be interested in endocrine hypertension and should read this volume if they want to have
adequateknowledgeoftheseconditionsandbeabletopracticeevidence-baseddiagnosisandmanagementofhypertensive
patients, many of whom will have some form of endocrine hypertension, very often primary aldosteronism, but occa-
sionally some of the more rare forms of endocrine hypertension.
Ernesto L. Schiffrin, C.M., MD, Ph.D., FRSC, FRCPC, FACP
Physician-in-Chief, Sir Mortimer B. Davis-Jewish General Hospital, Director, Hypertension and Vascular
Research Unit, Lady Davis Institute for Medical Research, Distinguished James McGill Professor and
Associate Chair, Department of Medicine, McGill University
Editor-in-Chief, The American Journal of Hypertension
v
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Contents
Contributors xv Imaging for patients with endocrine
Editors’ brief resumes xvii hypertension 8
Invited senior authors’ profiles xix Systematic approach for the diagnosis and
Preface xxvii management of endocrine hypertension 9
Recent trends/emerging concepts 9
1. Endocrine hypertensiondan Genetic testing for familial PPGL 10
overview
Genetic testing for familial
hyperparathyroidism 10
JosephM.Pappachan and Genetic testing for familial hyper-
CorneliusJ.Fernandez aldosteronism especially GRA 11
Introduction 2 Conclusions 13
Primary hypertension versus secondary References 14
hypertension 2
Individual chapters 3 2. Catecholamines and blood
Catecholamines and blood pressure pressure regulation
regulation 3
Adrenocortical hormones and BP CorneliusJ.Fernandez, FahmyW.F.Hanna,
regulation 3 KarelPacakand MatthewA.Nazari
Hypothalamicepituitaryeadrenal axis and Introduction 20
blood pressure regulation 3 Catecholamines and autonomic physiology 20
Renin-angiotensinealdosterone system and The synthesis, storage, and regulation of
blood pressure regulation 4 catecholamines 20
Monogenic hypertension: an overview 4 Metabolism of catecholamines 22
Primaryaldosteronism (Conn’s syndrome) 4 Adrenoceptors, subtypes, and associated
Familial hyperaldosteronism 5 second messenger systems 23
Congenital adrenal hyperplasia and Neuroendocrine effects of catecholamines
hypertension 5 on blood pressure 25
Endocrine hypertension: discovering the Metabolic regulation by catecholamines 26
inherited causes 5 Biologic effects 26
Pheochromocytomas and Summarizing the net effect of catechol-
hypertension 6 amines onvascular hemodynamics 26
Paragangliomas and hypertension 6 PPGLs and excess catecholamine states 28
ACTH-dependent Cushing syndrome 6 Deleterious cardiac effects of excess cat-
Adrenal Cushing’s syndrome 7 echolamines: CICMP 28
Hypertension in growth hormone excess Stress cardiomyopathy: impaired adreno-
(acromegaly) and deficiency 7 ceptor and second messenger signaling 28
Hypertension in thyroid disease and Hypertrophic cardiomyopathy: load-
hyperparathyroidism 7 dependent and nonload-dependent
Obesity, insulin resistance, and obstructive remodeling 29
sleep apnea 7 Dilated cardiomyopathy: cardiotoxic
Endocrine hypertension in children 8 effects of catecholamines 29
Endocrine hypertension in pregnant Deleterious vascular effects of
woman 8 catecholamines 31
vii
viii Contents
4. Hypothalamicepituitaryeadrenal
Catecholamines and alterations in renal
physiology 31 axis and blood pressure
Catecholamines and other organs 31 regulation
Catecholamines and autonomic failure 31
Summaryand conclusions 32 JosephM.Pappachan,CorneliusJ.Fernandez
Learning points 32 andConstantineA.Stratakis
References 32 Introduction 54
Physiologyof blood pressure regulation
3. Adrenal cortical hormones and and HPA axis 54
blood pressure regulation
POMC (pro-opiomelanocortin): its role in
metabolism and energy balance 54
AnnaSanders, CorneliusJ.Fernandez
CRH (corticotropin-releasing hormone) and
andRousseauGama
AVP (arginine vasopressin) control the
Introduction 36 expression of POMC (pro-
Physiological aspects 36 opiomelanocortin) 55
An overview of adrenal steroid synthetic Pathophysiologyof hypertension and HPA
pathways 36 axis 55
Regulation of steroidogenesis: cholesterol, HPA axis and autonomic nervous system
StAR, and p450scc 36 (in relation to BP) 56
Aldosterone synthesis in the zona HPA axis, adrenal hormones, and blood
glomerulosa 37 pressure 57
Cortisol synthesis in the zona fasciculata 38 HPA axis and metabolic syndrome 57
Adrenal androgen synthesis and regulation HPA axis, various hormonal disorders, and
in the zona reticularis 39 hypertension 57
The glucocorticoid receptor (GR) 40 Summary and conclusions 60
Glucocorticoid receptor and blood Learning points 60
pressure regulation 41 References 60
The mineralocorticoid receptor 42
MR and blood pressure regulation: 5. Renineangiotensinealdosterone
genomic effects 42 system and blood pressure
MR and blood pressure: non-genomic regulation
actions 42
Androgens, receptors, and cardiovascular GinoSeravalleandGuidoGrassi
system effects 43 Introduction 64
Pathophysiological alterations in Physiological aspects of RAAS 65
adrenocortical hormones and effects on RAAS, inflammation, and remodeling 66
cardiovascular homeostasis 45 RAAS blocking agents and
Glucocorticoid excess states (including cardiovascular protection in
non-neoplastic Cushing’s) 45 hypertension 67
Mineralocorticoid excess states: primary ACE inhibitors 67
aldosteronism (PA) and familial ARBs 68
hyperaldosteronism 45 Direct renin inhibitors 69
Apparent mineralocorticoid excess 46 Dual RAAS inhibition 69
Androgen deficiency/excess states ACEI versus ARBs 69
(including congenital disorders such as Mineralocorticoid receptor
CAH) 46 antagonists 70
Emerging research questions 46 Conclusions 71
Summaryand conclusions 47 Learning points 71
Learning points 47 References 71
References 47
Contents ix
6. Monogenic hypertension: an 9. Congenital adrenal hyperplasia
overview and hypertension
CorneliusJ.Fernandez, JosephM.Pappachan Busra GurpinarTosunandTulayGuran
and UteI.Scholl Introduction 114
Introduction 78 Genetics of CAH (in generaldall forms) 114
Genetics of monogenic hypertension 79 Pathophysiologyof hypertension in CAH 116
Summary 85 11b-hydroxylase deficiency 118
Learning points 85 Clinical presentations 118
References 85 Diagnostic approach for 11b-hydroxylase
deficiency 118
7. Primary aldosteronism
Management algorithm 119
(Conn’s syndrome)
Therapeutic targets 119
17a-hydroxylase deficiency 119
Filippo Ceccato,Irene Tizianel,
Clinical presentation 119
GiacomoVoltanand FrancoMantero
Diagnostic approach 120
Introduction 90 Management algorithm 120
The renineangiotensinealdosterone system 91 Therapeutic targets 120
Who should be screened? (The epidemiol- Overtreatment of CAH 120
ogyof primaryaldosteronism) 92 When to suspect of CAH in patients with
Aldosteroneerenin ratio as hypertension 121
screening test 92 Future research 121
Confirmatory test after positive ARR 93 Summary and conclusions 122
Subtyping in primary aldosteronism: Learning points 122
adrenal vein sampling or imaging? 95 References 122
Laparoscopic surgery and peri-operative
management 96 10. Endocrine hypertension:
Medical therapyof primary aldosteronism 96 discovering the inherited causes
Familial forms of primaryaldosteronism 98
Conclusions 99 FarahnakAssadi, NakysaHooman,Mojgan
Learning points 99 Mazaheriand FatemehGhaneSharbaf
References 100 Introduction 128
Inherited disorders of endocrine
8. Familial hyperaldosteronism 105 hypertension 129
Monogenic hypertension associated with
JosephM.Pappachan, Cornelius J.Fernandez suppressed PAC and PRA 131
and DavidS.Geller
Liddle syndrome 131
Introduction 106 Congenital adrenal hyperplasia (CAH) 134
Pathophysiologyof familial
Apparent mineralocorticoid excess (AME) 135
hyperaldosteronism 106 Geller syndrome 137
Subtypes of familial hyperaldosteronism 106 Monogenic hypertension associated with
Familial hyperaldosteronism type 1 106 normal PAC and low PRA 137
Familial hyperaldosteronism type 2 108 Pseudohypoaldosteronism type II (Gordon
Familial hyperaldosteronism type 3 109 syndrome) 137
Familial hyperaldosteronism type 4 109 Monogenic hypertension associated with
PASNA syndrome 110 high PAC and low PRA 138
Emerging research questions/future Familial hyperaldosteronism type 1 (FH-1)
research 110 or glucocorticoid suppressible
Summary and conclusions 110 aldosteronism 138
Learning points 110 Familial hyperaldosteronism type 2 (FH-2) 139
References 111 Familial hyperaldosteronism type 3 (FH-3) 139