Lec 5
Dr. Yasammen Alsaffar
Hyperaldosteronism
The prevalence of hyperaldosteronism as many as 10% of people with
hypertension. Indications to test for mineralocorticoid excess in hypertensive
patients include hypokalaemia (including hypokalaemia induced by thiazide
diuretics), poor control of blood pressure with conventional therapy, a family
history of early-onset hypertension, or presentation at a young age.
Causes:
With high renin and high aldosterone (secondary hyperaldosteronism)
1• Inadequate renal perfusion (diuretic therapy, cardiac failure, liver failure,
nephrotic syndrome, renal artery stenosis).
2• Renin-secreting renal tumour (very rare).
With low renin and high aldosterone (primary hyperaldosteronism)
1• Adrenal adenoma secreting aldosterone (Conn’s syndrome).
2• Idiopathic bilateral adrenal hyperplasia.
Most individuals with primary hyperaldosteronism have bilateral adrenal
hyperplasia (idiopathic hyperaldosteronism), while only a minority have an
aldosterone-producing adenoma (Conn’s syndrome).
Clinical features
Individuals with primary hyperaldosteronism are usually asymptomatic but may
have features of sodium retention or potassium loss. Sodium retention may
cause oedema, while hypokalaemia may cause muscle weakness, polyuria
(secondary to renal tubular damage, which produces nephrogenic diabetes
insipidus) and occasionally tetany (because of associated metabolic alkalosis
and low ionised calcium). Blood pressure is elevated but accelerated phase
hypertension is rare.
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Investigations
Biochemical
Routine blood tests may show a hypokalaemic alkalosis. Sodium is usually at
the upper end of the reference range in primary hyperaldosteronism, but is
characteristically low in secondary hyperaldosteronism (because low plasma
volume stimulates antidiuretic hormone (ADH) release and high angiotensin II
levels stimulate thirst).
The key measurements are plasma renin and aldosterone, and in many centres,
the aldosterone: renin ratio (ARR) testing is positive if plasma aldosterone
concentration is frankly elevated (>15 ng/dL), plasma renin activity is
suppressed, and a ratio of the aldosterone over the renin is greater than 20.
Imaging and localization
Imaging with CT or MRI to adrenal glands to localize the lesion.
Management
Mineralocorticoid receptor antagonists (spironolactone and eplerenone) are
valuable in treating both hypokalaemia and hypertension in all forms of
mineralocorticoid excess. Up to 20% of males develop gynaecomastia on
spironolactone. Amiloride, which blocks the epithelial sodium channel
regulated by aldosterone, is an alternative.
In patients with a Conn’s syndrome, medical therapy is usually given for a few
weeks to normalize whole-body electrolyte balance before unilateral
adrenalectomy.
Phaeochromocytoma and paraganglioma
These are rare neuro-endocrine tumours that may secrete catecholamines
(adrenaline, noradrenaline). Approximately 80% of these tumours occur in the
adrenal medulla (phaeochromocytomas), while 20% arise elsewhere in the body
in sympathetic ganglia (paragangliomas). Most are benign but approximately
15% show malignant features. Around 30% are associated with inherited
disorders, including neurofibromatosis, and MEN 2.
Clinical features
phaeochromocytoma accounts for less than 0.1% of cases of hypertension.
The clinical features include:
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• Hypertension (usually paroxysmal followed by postural drop of blood
pressure)
• Paroxysms of: Pallor (occasionally flushing), Palpitations, sweating, Headache
and Anxiety.
• Abdominal pain, vomiting.
• Constipation.
• Weight loss.
• Glucose intolerance.
Investigations
Excessive secretion of catecholamines can be confirmed by measuring
metabolites in plasma and/or urine (metanephrine and normetanephrine) but
there is a high ‘false-positive’ rate.
Serum chromogranin A is often elevated and may be a useful tumour marker.
Localisation
Phaeochromocytomas are usually identified by abdominal CT or MRI.
Localisation of paragangliomas may be more difficult. Scintigraphy using
(MIBG) can be useful, particularly if combined with CT. PET is especially
useful for detection of malignant disease and for confirming an imaging
abnormality as a paraganglioma.
Management
Medical therapy is required to prepare the patient for surgery, preferably for a
minimum of 6 weeks to allow restoration of normal plasma volume. The most
useful drug in the face of very high circulating catecholamines is the
α-blocker
phenoxybenzamine because it is a non-competitive antagonist, unlike prazosin
or doxazosin. If
α-blockade produces a marked tachycardia, then a β-blocker
such as propranolol can be added. Shouldn't give a
β-blocker before anα-
blocker, as this may cause a paradoxical rise in blood pressure due to unopposed
α-mediated vasoconstriction.
During surgery, sodium nitroprusside and the short-acting
α-antagonist
phentolamine are useful in controlling hypertensive episodes, which may result
from anaesthetic induction or tumour mobilisation. Post-operative hypotension
may occur and require volume expansion and, very occasionally, noradrenaline
(norepinephrine) infusion, but is uncommon if the patient has been prepared
with phenoxybenzamine.
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Adrenal insufficiency
Adrenal insufficiency results from inadequate secretion of cortisol and/or
aldosterone. It is potentially fatal and notoriously variable in its presentation.
A high index of suspicion is therefore required in patients with unexplained
fatigue, hyponatraemia or hypotension.
Causes:
A- Secondary (
↓ACTH)
1- Withdrawal of suppressive glucocorticoid therapy.
2- Hypothalamic or pituitary disease.
B- Primary (
↑ACTH)
Addison’s disease
1- Autoimmune: either Sporadic or Polyglandular syndromes
2- Tuberculosis.
3- HIV/AIDS.
4- Metastatic carcinoma.
5- Bilateral adrenalectomy.
6- Intra-adrenal haemorrhage (Waterhouse– Friedrichsen syndrome following
meningococcal septicaemia)
7- Amyloidosis.
Clinical assessment
1- Glucocorticoid insufficiency (in all patients)
a- Weight loss, anorexia, Nausea, vomiting, and Diarrhea or constipation.
b- Malaise, weakness.
c- Postural hypotension, Shock.
d- Hypoglycaemia, hyponatraemia (dilutional) and hypercalcaemia.
2- Mineralocorticoid insufficiency: (in patient with Addison disease)
a- Hypotension, Shock.
b- Hyponatraemia (depletional) and hyperkalaemia.
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3- ACTH excess: (in patient with Addison disease)
Pigmentation of sun-exposed areas and pressure areas (e.g. elbows, knees),
palmar creases, mucous membranes conjunctivae, and recent scars.
4- Adrenal androgen insufficiency: (in all patients):
Decreased body hair and loss of libido, especially in female.
Features of an acute adrenal crisis include circulatory shock with severe
hypotension, hyponatraemia, hyperkalaemia and, in some instances,
hypoglycaemia and hypercalcaemia.
Investigations
Treatment should not be delayed to wait for results in patients with suspected
acute adrenal crisis. Here, a random blood sample should be stored for
subsequent measurement of cortisol and, if the patient’s clinical condition
permits, it may be appropriate to spend 30 minutes performing a short ACTH
stimulation test before administering hydrocortisone. Investigations should be
performed before treatment is given in patients who present with features
suggestive of chronic adrenal insufficiency.
All patients should be sent for electrolyte (hyponatraemia, hyperkalemia,
hypercalcaemia) and glucose may be low (hypoglycemia).
Assessment of glucocorticoids
Random plasma cortisol is usually low in patients with adrenal insufficiency but
it may be within the reference range, so more useful is the short ACTH
stimulation test, in which cortisol levels fail to increase in response to
exogenous ACTH in patients with primary or secondary adrenal insufficiency.
These can be distinguished by measurement of ACTH (which is low in ACTH
deficiency and high in Addison’s disease).
Assessment of mineralocorticoids
Hyperkalaemia.
Plasma renin increase.
Plasma aldosterone low.
Assessment of adrenal androgens
This is not necessary in men.
In women, dehydroepiandrosterone (DHEA) is low.
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Other tests to establish the cause
Patient with low ACTH should be investigated for any pituitary diseases.
In patients with elevated ACTH send for:
1- Adrenal autoantibodies. If –ve so continue to:
2- Imaging of the adrenal glands with CT or MRI is indicated.
3- Tuberculosis causes adrenal calcification, visible on plain X-ray or
ultrasound scan.
4- An HIV test should be performed if there are risk factors.
Management
Glucocorticoid replacement
Adrenal replacement therapy consists of oral hydrocortisone (cortisol) 15–20
mg daily in divided doses, typically 10 mg on waking and 5 mg at around 1500
hrs. These are physiological replacement doses which should not cause
cushingoid side-effects.
Special condition:
1- Febrile illness: we should double dose of hydrocortisone.
2- Surgery:
• Minor operation: hydrocortisone 100 mg IM with pre-medication
• Major operation: hydrocortisone 100 mg 4 times daily for 24 hours, then 50
mg IM 4 times daily until ready to take tablets.
3- Vomiting: Patients must have parenteral hydrocortisone if unable to take it by
mouth.
Mineralocorticoid replacement( inAddison'sdisease)
Fludrocortisone is administered at the usual dose of 0.05–0.15 mg daily, and
adequacy of replacement may be assessed by measurement of blood pressure,
plasma electrolytes and plasma renin.
Androgen replacement
Androgen replacement with DHEA (50 mg/day) is occasionally given to women
with primary adrenal insufficiency.
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Adrenal crises:
Correct volume depletion
• IV saline as required to normalise blood pressure and pulse.
• In severe hyponatraemia (<125 mmol/L) avoid increases of plasma Na >10
mmol/L/day to prevent pontine demyelination.
• Fludrocortisone is not required during the acute phase of treatment.
Replace glucocorticoids
• IV hydrocortisone succinate 100 mg stat, and 100 mg 4 times daily for first
12–24 hours
• Continue parenteral hydrocortisone (50–100 mg IM 4 times daily) until patient
is well enough for reliable oral therapy.
Correct other metabolic abnormalities
• Acute hypoglycaemia: IV 10% glucose
• Hyperkalaemia: should respond to volume replacement but occasionally
requires specific therapy.
With best wishes
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