27th May 2025

Primary hyperaldosteronism

Background

In primary hyperaldosteronism (PH), aldosterone production is increased, usually in an autonomous fashion independent of the renin aldosterone angiotensin (RAAS) system in primary aldosteronism, whereas secondary hyperaldosteronism occurs due to high renin levels. 

High aldosterone levels lead to excessive sodium retention in the distal renal tubule, and concomitant urinary excretion of potassium and hydrogen ions. This leads to water retention, causing hypertension and suppression of the RAAS system, alongside hypokalaemia and metabolic alkalosis in severe cases.

Epidemiology

The most common cause of secondary hypertension in middle-aged adults is PH, accounting for 5 – 10% of cases. Approximately 20% of patients will have hypokalaemia, and therefore screening in hypertension is warranted regardless of potassium levels.

Aetiology

Excessive aldosterone production occurs due to adrenal adenoma (also known as Conn’s syndrome) in 80% of cases, idiopathic bilateral adrenal hyperplasia in 15% of cases, familial hyperaldosteronism type I and II, or adrenal carcinoma. Adrenal adenomas are more common in females, whilst bilateral adrenal hyperplasia more commonly occurs in males past the age of 40.

Diagnosis

Risk factors in the history that could indicate primary hyperaldosteronism include:

• Early age of onset of hypertension (<35 years).
• Positive family history of PH, or early onset hypertension and/or stroke.
• Accelerated and/or resistant hypertension (e.g. resistant to >3 drugs).
• Unusual symptoms e.g. weakness, sweating attacks.
• Hypokalaemia prior to diuresis.

The first-line investigations often centre around testing of the RAAS system, and therefore drugs that may influence this system must be stopped in advance e.g. ACE inhibitors, spironolactone and angiotensin II receptor blockers. Typical findings are:

• Raised plasma aldosterone : renin ratio (ARR).
• Raised plasma aldosterone levels.
• Suppressed plasma renin.
• Hypokalaemia which can cause weakness.
• Urinary potassium loss.
• Metabolic alkalosis and elevated bicarbonate.

To differentiate whether an adrenal adenoma or bilateral adrenal hyperplasia is responsible for excess aldosterone secretion, a CT or MRI is warranted. Selective adrenal venous sampling can be done to localise the cause of primary aldosteronism. 

Confirmatory tests include a fludrocortisone suppression test, where fludrocortisone (0.1 mg / 6 hours), sodium and potassium supplementation are administered for 4 days. On the 4th day, a cortisol level is measured at 7 am, and renin, cortisol and aldosterone levels are measured at 10 am. A serum aldosterone >6 ng/dL, renin < 1 ng/mL/hr and potassium in normal range is diagnostic. If cortisol is lower at 10 am than at 7 am, this also excludes a confounding ACTH effect. A saline infusion test is an alternative confirmatory test, whereby renin, aldosterone, cortisol and potassium are measured prior to and after administration of 2 L of normal saline. A serum aldosterone > 10 ng/dL is diagnostic, whilst < 5 ng/dL rules out PH and values in between are indeterminate. Other confirmatory tests include oral sodium loading and the captopril challenge test.

Management

Management will depend on whether PH is due to a unilateral issue e.g. adenoma or bilateral, and whether the patient is fit for surgery. In the instance of unilateral causes, laparoscopic adrenalectomy may be performed and can resolve hypertension in 70% of patients. Even for bilateral causes, unilateral laparoscopic adrenalectomy can be of benefit by reducing the amount of adrenal tissue capable of secreting aldosterone, and therefore reduce hypertension. If unfit for surgery, lifelong aldosterone antagonists may be prescribed (such as spironolactone, amiloride or eplerenone) and these can take weeks to months to improve hypertension. Treatment must be titrated to avoid excessive volume depletion that can result in pre-renal acute kidney injury and hyperkalaemia. Dietary sodium restriction is also of benefit.

Complications

The main complications of PH are due to hypertension and include increased risk of cerebrovascular accident, myocardial infarction, heart failure, atrial fibrillation and chronic kidney failure. Excessive aldosterone can result in myocardial fibrosis, but this is ameliorated with treatment with aldosterone antagonists.