Endocrinology

Lec 4

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.

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:

• 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.