27th May 2025

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.