What is the suggested workup for a patient with suspected hyperaldosteronism?

From the Guidelines

The workup for suspected hyperaldosteronism begins with screening through plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio testing, ideally after discontinuing interfering medications like diuretics, ACE inhibitors, and ARBs for 2-4 weeks, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.

Key Steps in the Workup

• Discontinue interfering medications for 2-4 weeks before testing
• Perform plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio testing
• Use a cutoff value of 30 when plasma aldosterone concentration is reported in nanograms per deciliter (ng/dL) and plasma renin activity in nanograms per milliliter per hour (ng/mL/h) 1
• Confirmatory testing may include oral sodium loading, saline infusion, fludrocortisone suppression, or captopril challenge tests to demonstrate autonomous aldosterone production

Subtype Differentiation and Treatment

• Adrenal imaging (CT or MRI) to identify potential adenomas
• Adrenal vein sampling to lateralize aldosterone production, particularly if surgical treatment is being considered
• Surgical removal of the offending adrenal gland for unilateral primary aldosteronism
• Medical treatment with mineralocorticoid receptor antagonists (MRAs) such as spironolactone or eplerenone for bilateral primary aldosteronism or nonsurgical candidates 1

Important Considerations

• Normalize serum potassium with potassium supplements or potassium-sparing diuretics like spironolactone (25-100 mg daily) before testing, as hypokalemia can suppress aldosterone production and lead to false-negative results
• The use of newer agents, such as the non-steroidal MRAs finerenone and esaxerenone, and the aldosterone synthase inhibitor baxdrostat, is being tested for treating primary aldosteronism 1

From the Research

Suggested Workup for Hyperaldosteronism

The suggested workup for a patient with suspected hyperaldosteronism involves several steps:

• Screening tests should not be based on recognition of hypokalemia alone, as at least 20% of patients with primary aldosteronism have normal serum potassium levels 2
• The diagnosis depends on identifying renin suppression and measuring the ratio of plasma aldosterone concentration to plasma renin activity (ARR) 2, 3
• The ARR is a valid screening assay for primary aldosteronism, and discontinuation of antihypertensive medications is not needed for this test 3
• A plasma aldosterone-renin ratio (ARR) greater than 100 ng/dL per ng/mL/h is considered elevated, and further diagnostic workup is recommended for these patients 3

Diagnostic Tests

The following diagnostic tests may be used to confirm the diagnosis of hyperaldosteronism:

• Aldosterone suppression test after oral salt loading 2
• Postural hormonal testing to detect a unilateral source of aldosterone 2
• Selective venous sampling (SVS) with measurement of aldosterone concentrations in each adrenal vein to confirm the diagnosis and localize the source of aldosterone excess 2
• Adrenal computed tomography and/or magnetic resonance imaging to visualize the adrenal glands 3
• Adrenal iodine 131 norcholesterol uptake scan to assess adrenal function 3

Interpretation of Test Results

The interpretation of test results is crucial in the diagnosis of hyperaldosteronism:

• An elevated ARR is a sensitive and specific indicator of primary aldosteronism 4
• The cutoff level for ARR varies depending on the condition of testing, such as posture and time of day 4
• A low plasma renin level (<0.5 pmol/mL/h) is a simple and sufficient way to detect spironolactone-responders among patients with resistant hypertension 5
• A plasma aldosterone level greater than 400 pmol/L together with a low plasma renin level should trigger further investigations for an adrenal adenoma 5

Clinical Considerations

Clinical considerations are important in the workup for hyperaldosteronism:

• The adjustment of antihypertensive treatment during screening for primary aldosteronism can cause severe side effects, such as hypertensive crisis, atrial fibrillation, and heart failure 6
• The use of mineralocorticoid antagonists, such as spironolactone, can help control blood pressure and potassium levels in patients with primary aldosteronism 5, 6