Endocrine Hypertension

English Course of Medicine
Course of Endocrinology and

Medical Sexology
Prof.ssa Simona Frontoni

Department of Systems Medicine
e-mail: frontoni@uniroma2.it
Endocrine hypertension
CAUSES OF SECONDARY HYPERTENSION
Classification
RENAL HYPERTENSION
 Renovascular (atheroma, fibromuscular dysplasia)
 Renal parenchymal disease
 Primary hyperreninism (iuxtaglomerular or ectopic
tumor)
PRIMARY HYPERALDOSTERONISM
 Monolateral adrenal adenoma (70%)
 Bilaterla hyperplasia glomerulosa (25%)
 Adrenal carcinoma (<2%)
RARE CAUSES
 Pheochromocytoma
 Cushing’s syndrome
 Aortic coarctation
Adrenal hormone production
adrenal
glomerulosa
fasciculata
reticularis
gonad
periphery
medulla
TH DDC DBH PNMT

tyrosine DOPA dopamine norepinephrine epinephrine
Renin-Angiotensin-Aldosterone AXIS
Aldosterone increases:
Na resorption
K + H excretion
MINERALCORTICOID HYPERTENSION
Renin-angiotensin-aldosterone axis
Secondary hyperaldosteronism
Primary hyperaldosteronism
Classification
RENIN (R)
ALDOSTERONE (A)
R R R
A A A
PRIMARY SECONDARY
• RARE
HYERALDOSTERONISM HYERALDOSTERONISM
Clinical features
 SEVERE HYPERTENSION
 IPOKALIEMIA AND METABOLIC ALKALOSIS
 MODEST HYPERNATRIEMIA
 MODEST HYPOMAGNESEMIA
 NO EDEMA
 FATIGUE, LOSS OF STAMINA, CRAMPS, POLYURIA,

POLYDIPSIA
 ORTHOSTATIC HYPOTENSION
Hyperaldosteronism
screening
 HYPERTENSION AND HYPOKALIEMIA
 SEVERE AND RESISTANT HYPERTENSION
 ADRENAL INCIDENTALOMA
Hormonal assessment
Basal conditions:
around 8 A.M. after at least 4 hrs. of
recumbency (unrestricted salt diet): PRA, plasma
aldosterone
Stimulation test:
a 4-hour upright posture  furosemide i.v.
ADENOMA: suppression of PRA, high basal plasma aldosterone level,
no significant change or a frank decrease on stimulation.
HYPERPLASIA: suppression of PRA, lower basal plasma aldosterone
level (< 25 ng/dl), an increase on stimulation
Saline infusion test (suppression):
2 L 0.9% NaCl over 2 hrs.: no suppression of plasma
aldosterone
Hyperaldosteronism
phamacological interference
SPIRONOLACTON R A 6 WEEK-WASHOUT
DIURETICS R A
ACE-INHIBITORS AND R A 2 WEEK-WASHOUT

AT1-RC ANTAGONISTS
-BLOCKERS R =A
CA-ANTAGONISTS and minor interferences ALLOWED

ALFA-BLOCKER
diagnostic flow-chart
RENIN and ALDOSTERONE assay
(recumbency 8am – upright posture 3h)
No increase or decrease of aldosterone Increase of aldosterone
SUSPECTED ADENOMA SUSPECTED HYPERPLASIA
CT or MRI
Normal/
ADENOMA
doubtful
 Adrenal scintigraphy
LAPAROSCOPIC (131I-iodocholesterol)
ADRENALECTOMY  Adrenal vein sampling
Goals of treatment
 BP normalization
 K+ normalization
 Aldosterone value normalization or
receptor blockade
Medical treatment
Spironolacton (Aldactone)
 Mineralcorticoid receptor blockade, androgens and
progesterone
 Side effects: impotece, ↓libido, gynecomastia, amenorrhea
Eplerenone (Inspra)
 Highly selective Mineralcorticoid receptor blockade
 Few side effects
 Expensive
Amiloride, triamterene
 Aldosterone receptor blocakde, at the level of the kidney
 Persistence of heart effects of hyperaldosteronism
Location of adenoma and treatment
Adenoma: unilateral adrenalectomy
Hyperplasia: spironolactone
Preoperative preparation:
Spironolactone:
- 200-300 mg/d (4-6 weeks)
- maintenance dose 75-100 mg/d
- Amiloride: 20-40 mg/d
Other antihypertensive drugs (Ca channel blockers)
Surgery
 IPOKALIEMIA ALMOST INVARIABLY CORRECTED
 RESOLUTION OR IMPROVEMENT OF HYPERTENSION

IN 30-60 %
 GENERALLY, NO HYPOSURRENALISM
 INFREQUENTLY, TRANSIENT HYPERKALIEMIA AND

HYPOSODIEMIA (INHIBITION OF RAA AXIS)  HIGH
NA DIET AND POSSIBLE SHORT TREATMENT WITH
FLUDROCORTISONE
PHEOCHROMOCYTOMA
Definition and incidence
DEFINITION:
Tumor arising from chromaffin cells, that release
catecholamines (epinephrine and norepinephrine),
inducing a clinical picture related to them.
INCIDENCE:
 0,2-0,5% of patients undergoing a screening for
hypertension
 4-10% of patients with “ adrenal incidentalomas”
PHEOCHROMOCYTOMA
nosographic characteristics
 90% adrenal localization

 10% extra-adrenal localization (paragangliomas)
 90% benign tumors

 10% malignant tumors
 90% sporadic tumors

 10% familial tumors *
* It has recently been shown that ¼ of sporadic tumors

display germline mutations.
PHEOCHROMOCYTOMA
Familial types
 MEN 2A: mutation proto oncogene RET
 MEN 2B: mutation proto oncogene RET. Autosomal

dominant high penetrance inheritance pattern.
 M. di Von Hippel Lindau: mutation oncosuppressor

gene VHL
 M. di Von Recklinghausen: mutation gene NF1
 Primary paragangliomas: mutation genes subunit B, D

or C of succinate dehydrogenase ubiquinone in
mitochondria
PHEOCHROMOCYTOMA
Clinical manifestations
SYMPTOMS % SIGNS %
Headache 76-100% Hypertension 76-100%

Forceful heartbeat 51-75% Tachycardia 51-75%
Sweating 37-71% Postural hypotension 51-75%
Anxiety or irritability 26-50% Hypertensive paroxysms 26-50%
Abdominal pain 14-62% Polypnea 26-50%
Chest pain 26-50% Fasting hyperglycemia 26-50%
Nausea 10-42% Weight loss 1-25%
Dyspnea 15-39% Facial pallor 1-25%
Tremors 13-38% Flushing 4-19%
Fatigue 20-30%
Heat intolerance 1-25%
Visual disturbances 1-25%
Constipation 1-25%
Sensitivity: 90.9%
Symptomatologic Triade + hypertension Specificity: 93.8%
PHEOCHROMOCYTOMA
Hypertension
PATHOGENESIS
 Excessive release of catecholamines by the tumor
 Increased HR and PVR
 Increased myocardial contractility
 Reduced venous compliance
CHARACTERISTICs
 Paroxysms: 26%-56%
 Persistent: 39% (>> in children)
 Normal BP: 13%
 Resistent to common anti-hypertensive treatment
PHEOCHROMOCYTOMA
Screening
 YOUNG HYPERTENSIVE PATIENTS
 HYPERTENSIVE PATIENTS WITH:

- typical symptoms (headache, sweating, forceful heartbeat)
- paroxysmal hypertension
- orthostatic hypotension
- hypertension unresponsive to treatment
 CLINICAL PICTURE SUGGESTIVE FOR FAMILIAR FORMS
 ADRENAL INCIDENTALOMA
 “ADRENERGIC CRISIS” DURING ANESTHESIA AND/OR
SURGERY
 HYPERTENSION DURING PREGNANCY WITHOUT PRE-
ECLAMPSIA
PHEOCHROMOCYTOMA
biochemical diagnosis
BIOCHEMICAL TESTS SENSITIVITY % SPECIFICITY %

Plasma “free”
99 89
metanephrines
Urinary “fractionated”
97 69
metanephrines
Urinary catecholamines 86 88
Plasma catecholamines 84 80
Total urinary
77 93
metanephrines
VMA (urinary
64 95
vanillylmandelic acid)
PHEOCHROMOCYTOMA
biochemical diagnosis
Glucagon test:
1 mg i.v., phentolamine (Regitine) should be available to
terminate the induced episode. Sensitivity: 90%.
Clonidine suppression test:

0.3 mg of clonidine p.o. 2-3 hrs. before sampling of blood for
plasma NA level: no reduction of plasma NA
Trial of phenoxybenzamine (Dibenzyline): 2-receptor blocker

PHEOCHROMOCYTOMA
biochemical diagnosis: pharmacological interferences
 TRICYCLIC ANTIDEPRESSANTS
 AMPHETAMINES
 LEVODOPA
 ADRENERGIC AGONISTS
 PROCHLORPERAZIN, ACETAMINOPHEN, METOCLOPRAMIDE
 RESERPINE, CLONIDINE
 ETHANOL
PHEOCHROMOCYTOMA
LOCATION
CT MRI
Sensitivity Sensitivity
93-100% adrenal = CT in adrenal
~90% extra-adrenal ≥ CT, in extra-adrenal
Both CT and MRI display a low specificity
MIBG
Specificity > TC and MRI (98 – 100 %)
Sensitivity < CT and MRI (90%)
Useful in the diagnosis of extra-adrenal tumors and
methastasis
PET with 6-[18F]-fluorodopamine
Sensitivity > MIBG
OCTREOSCAN
PHEOCHROMOCYTOMA
Treatment
SURGERY
 Therapy of choice (mortality 0-2.7% vs. 25-50% in
1950)
 Laparoscopic approach preferred
MEDICAL THERAPY
 Hypertensive paroxysms
 Pre-operative preparation
 After surgery
PHEOCHROMOCYTOMA
Pre-operative preparation
 CONTROL BP AND CARDIOVASCULAR SYMPTOMS
 REDUCTION OF ARRHYTHMIAS RISK
 PLASMA VOLUME EXPANSION
 REDUCTION OF RECEPTOR DOWN-REGULATION
 AVOID HYPOTENSIVE CRISIS AFTER SURGERY

PHEOCHROMOCYTOMA
Pre-operative preparation
At least 7-14 days
 CLINOSTATIC BP NO > 160/90
 ORTOSTHATIC BP NO < 80/45
 NO S-T AND T ECG ABNORMALITIES WITH VEB

< 1 EVERY 5’
PHEOCHROMOCYTOMA
Principles of therapy
1 1 2
Vasocostriction Increase in HR and Broncodilation

myocardial contractility Vasodilation
Increased renin
secretion
PHEOCHROMOCYTOMA
Treatment
Medical preoperative preparation:
Phenoxybenzamine (Dibenzyline)  propranolol when marked
tachycardia or arrhythmias
Prazosin  propranolol
Labetalol
Treatment of attacks:
Phentolamine (Regitine) 5-10 mg i.v.
Sodium nitroprusside – i.v. Infusion
Surgery:
Caution: induction of anesthesia
Phentolamine or sodium nitroprusside i.v. infusion
After tumour removal: blood volume expansion with whole
blood, plasma, or other fluids
PHEOCHROMOCYTOMA
general recommendations
 NO INTENSE PHYSICAL ACTIVITY

 NO SMOKE
 NO ALCOHOL
 NO SODIUM RESTRICTION
 NO INTERFERING DRUGS
PHEOCHROMOCYTOMA
drugs to be avoided
 D2 DOPAMINE RECEPTORS ANTAGONISTS

 TRICYCLIC ANTIDEPRESSANTS
 ANTIDEPRESSANTS INHIBITORS OF
SEROTONINE AND NOREPINEPHRINE REUPTAKE
 MAO INHIBITORS
 SIMPATHOMIMETICS
 OPPIOIDS E NEUROMUSCOLAR BLOCKERS *
 PEPTIDES AND STEROIDS *
* YES AFTER alfa BLOCKADE
RENOVASCULAR HYPERTENSION
WHEN RENOVASCULAR HYPERTENSION
SHOULD BE SUSPECTED?
1. Severe hypertension (diastolic pressure > 120 mmHg
with either progressive renal insufficiency or
refractoriness to agressive medical therapy (particularly
in a smoker or with other evidence of occlusive arterial
disease);
2. Accelerated or malignant hypertension with grade III or
grade IV retinopathy;
3. Moderate to severe hypertension in a patient with diffuse
atherosclerosis or a detected assymetry of kidney size;
4. An acute elevation in plasma creatinine level in a
hypertensive patient that is either unexplained or follows
therapy with an ACE inhibitor;
WHEN RENOVASCULAR HYPERTENSION
SHOULD BE SUSPECTED?
5. An acute rise in blood pressure over a previously stable

baseline;
6. A systolic-diastolic abdominal bruit;
7. Onset of hypertension below age 20 or above age 50;
8. Moderate to severe hypertension in patients with
recurrent acute pulmonary oedema;
9. Hypokalemia with normal or elevated plasma renin
levels in the absence of diuretic therapy;
10. A negative family history of hypertension.
Renal arteriography – a „golden standard
DSA – digital subtractive angiography
Captopril stimulation with measurement of PRA: exagerrated
induction of reactive hyperreninemia
Captoptil renoscintigraphy: 90% sensitivity and specificity
Doppler ultrasound
MRI imaging
Spiral CT scan
Treatment
Anatomic correction: surgery, angioplasty (PTCA)
Selective venous sampling for PRA (ratio affected kidney:
contralateral kidney > 1.5 indicates functional abnormality)
before anatomic correction
Medical treatment: ACE inhibitors, AT1 receptor antagonists
particularly effective; beta-blockers, Ca channel blockers,
methyldopa.
Sodium and fluid retention, expansion of ECFV and
plasma volume, increased cardiac output
Vasoconstriction, increased total peripheral
resistance
Typical features: hypertension, hypokalemia,
metabolic alkalosis, supression of the renin-angiotensin
system ( PRA),
Source of aldosterone: adenoma (75%),
micro- or macronodular hyperplasia (idiopathic
hyperaldosteronism) of zona glomerulosa
K+ depletion  impaired glucose tolerance, impaired urinary
concentrating ability, postural hypotension
Other hormones of zona glomerulosa:
DOC (deoxycorticosterone), corticosterone,
18-OH-corticosterone
Clinical features
Symptoms of hypokalemia: fatigue, loss of stamina,
weakness, lassitude, increased thirst, polyuria, paresthesias,
orthostatic hypotension
Symptoms of alkalosis: a positive Trousseau or Chvostek sign
Hypertension
No edema
The most common cause of hypokalemia in hypertensive
patients is diuretic therapy!
A low Na+ diet, by reducing delivery of Na+ to aldosterone-
sensitive sites in distal nephron, can reduce renal K+ secretion
and thus correct hypokalemia.
Average diet contains >120 mmol of Na+ per day
Hormonal assessment:
Plasma renin activity (PRA)
Plasma aldosterone
Urinary aldosterone excretion
PHEOCHROMOCYTOMA
Arises from chromaffin cells in the sympathetic nervous
system that release A, NA, and in some cases D
0.1% of patients with diastolic hypertension have
pheochromocytomas
In 50% of patients symptoms of are episodic/paroxysmal
Symptoms during or following paroxysms:

headache, sweating, facial pallor, cold and moist hands,
forceful heartbeat with or without tachycardia, anxiety or
fear of impending death, tremor, seizures, fatigue or
exhaustion, nausea and vomiting, abdominal or chest pain,
visual disturbances
Symptoms between paroxysms:
increased sweating, heat intolerance, cold hands and
feet, weight loss, constipation, wide fluctuations of blood
pressure, postural hypotension
PHEOCHROMOCYTOMA
With time attacks usually increase in frequency but do not
change much in character.
Glycosuria after an attack! ( glycogenolysis,  insulin release).
Paroxysms may be induced by deep palpation of the abdomen
Typically, commonly used antihypertensive drugs are ineffective
Location
Over 95% of pheochromocytomas are found in the abdomen,
and 85% of these are in the adrenal.
Chest: heart, posterior mediastinum
Multiple tumours in less than 10% of adults
Tumours are usually small (< 100 g)
Incidence of malignant tumours: 10%
Complications of hypertension are common: hypertensive

retinopathy or nephropathy, congestive heart failure, CVA, MI.
Common causes of death: MI, CVA, arrhythmias, irreversible
shock, renal failure, dissecting aortic aneurysm.

Endocrine Hypertension

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Endocrine Hypertension

Uploaded by

Copyright:

Available Formats

English Course of Medicine

Course of Endocrinology and

Prof.ssa Simona Frontoni

TH DDC DBH PNMT

 IPOKALIEMIA AND METABOLIC ALKALOSIS

 FATIGUE, LOSS OF STAMINA, CRAMPS, POLYURIA,

 HYPERTENSION AND HYPOKALIEMIA

 SEVERE AND RESISTANT HYPERTENSION

ACE-INHIBITORS AND R A 2 WEEK-WASHOUT

CA-ANTAGONISTS and minor interferences ALLOWED

No increase or decrease of aldosterone Increase of aldosterone

SUSPECTED ADENOMA SUSPECTED HYPERPLASIA

 Aldosterone value normalization or

 IPOKALIEMIA ALMOST INVARIABLY CORRECTED

 RESOLUTION OR IMPROVEMENT OF HYPERTENSION

 INFREQUENTLY, TRANSIENT HYPERKALIEMIA AND

 90% adrenal localization

 90% benign tumors

 90% sporadic tumors

* It has recently been shown that ¼ of sporadic tumors

 MEN 2B: mutation proto oncogene RET. Autosomal

 M. di Von Hippel Lindau: mutation oncosuppressor

 M. di Von Recklinghausen: mutation gene NF1

 Primary paragangliomas: mutation genes subunit B, D

Headache 76-100% Hypertension 76-100%

 HYPERTENSIVE PATIENTS WITH:

BIOCHEMICAL TESTS SENSITIVITY % SPECIFICITY %

Clonidine suppression test:

Trial of phenoxybenzamine (Dibenzyline): 2-receptor blocker

 PROCHLORPERAZIN, ACETAMINOPHEN, METOCLOPRAMIDE

Both CT and MRI display a low specificity

 CONTROL BP AND CARDIOVASCULAR SYMPTOMS

 REDUCTION OF ARRHYTHMIAS RISK

 PLASMA VOLUME EXPANSION

 REDUCTION OF RECEPTOR DOWN-REGULATION

 AVOID HYPOTENSIVE CRISIS AFTER SURGERY

At least 7-14 days

 CLINOSTATIC BP NO > 160/90

 ORTOSTHATIC BP NO < 80/45

 NO S-T AND T ECG ABNORMALITIES WITH VEB

Vasocostriction Increase in HR and Broncodilation

 NO INTENSE PHYSICAL ACTIVITY

 D2 DOPAMINE RECEPTORS ANTAGONISTS

5. An acute rise in blood pressure over a previously stable

Symptoms during or following paroxysms:

Complications of hypertension are common: hypertensive

You might also like