Primary aldosteronism is a condition caused by an excess of the adrenal hormone aldosterone independent of the renin-angiotensin-aldosterone axis.
It is increasingly being recognised as a common cause of secondary hypertension. Today prevalence is thought to be in the region 15 % of patients with hypertension.
Under normal conditions aldosterone release is primarily controlled by the renin-angiotensin system.
Renin, a proteolytic enzyme, is released by granular cells of the juxtaglomerular apparatus in response to:
In the blood renin cleaves angiotensinogen into angiotensin I.
Angiotensin-converting enzyme (ACE), found primarily in the vascular endothelium of the lungs, cleaves angiotensin I to give angiotensin II.
Angiotensin II has multiple functions:
Aldosterone is a mineralocorticoid released from the zona glomerulosa of the adrenal cortex. It is released in response to:
Its primary action is to increase the number of epithelial sodium channels in the distal tubule.
This results in sodium and water reabsorption and potassium excretion.
Despite the implied water and sodium retention, oedema is not a feature of primary aldosteronism. This is due to ‘aldosterone escape’.
This is a spontaneous diuresis that occurs in response to the water and sodium retention caused by raised aldosterone.
Aldosterone escape is not fully understood. Atrial natriuretic peptide, pressure natriuresis and changes to reabsorption in the distal tubule are thought to contribute to its mechanism.
In the vast majority of cases primary aldosteronism is caused by adrenal adenomas or adrenal hyperplasia.
This was previously termed Conn’s syndrome, a term that is now more generally used in an interchangeable manner with primary aldosteronism.
Once thought to be the most common cause of primary aldosteronism, it is implicated in around 30% of cases.
Now thought to be the most common cause of primary aldosteronism, adrenal hyperplasia is implicated in around 70% of cases.
It is normally bilateral (bilateral adrenal hyperplasia, BAH) but in rare cases is unilateral.
Adrenal carcinoma is a rare cause.
Frequently asymptomatic, clinical features of primary aldosteronism are those of hypokalaemia (30%) and hypertension.
Hypokalaemia may present with non-specific signs and symptoms. They include fatigue, muscle weakness and constipation.
Patients may develop hypokalaemia induced diabetes insipidus - manifesting with polyuria and polydipsia.
Long-standing hypertension may result in end-organ damage:
Hypertension, hypokalaemia and metabolic alkalosis are the classical findings.
Primary aldosteronism is now thought to be a significant cause of secondary hypertension.
Suspicion should be higher in younger patients and those with treatment-resistant hypertension.
Low serum levels are present in around 30% of patients. Urinary potassium may demonstrate inappropriate potassium loss in the setting of hypokalaemia.
In hypokalaemic patients, ECG's can show ST depression, T wave inversion and U waves.
Increased urinary hydrogen excretion, multifactorial, due to hypokalaemia and direct effects of aldosterone on intercalated cells may result in a metabolic alkalosis.
Diagnosis of primary aldosteronism requires a multi-tier testing approach.
The aldosterone:renin ratio (ARR) is used as a screen in those with suspected primary aldosteronism.
It compares serum levels of aldosterone and renin. A raised ratio should prompt further investigation.
Those with a raised ARR require confirmatory testing. A number of tests are available:
Once the diagnosis of primary aldosteronism is confirmed the exact aetiology must be identified. This can require complex testing often involving:
In those with a positive family history genetic testing should be considered.
Management of primary aldosteronism involves both surgical and medical modalities.
Medical management is used as a bridge to surgery. Aldosterone antagonists (e.g. spironolactone) may be given.
Surgical excision is the definitive therapy. Adrenalectomy, either laparoscopic or open, is the operation of choice.
Disease tends to be milder than that caused by adrenal adenomas.
Medical management is frequently used:
Other antihypertensives may be added. In cases of unilateral adrenal hyperplasia, adrenalectomy may be used.
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