What is the most sensitive diagnostic test for primary hyperaldosteronism (Primary Aldosteronism)?

From the Guidelines

The most sensitive diagnostic test for primary hyperaldosteronism is the plasma aldosterone concentration to plasma renin activity ratio (ARR), with a cutoff value of 30 ng/dL per ng/mL/h, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.

Key Considerations for ARR Testing

• The test should be performed in the morning after the patient has been upright for at least 2 hours, with blood samples collected between 8-10 AM.
• Interfering medications should be discontinued when possible, including spironolactone and eplerenone for 4-6 weeks; diuretics, ACE inhibitors, and ARBs for 2 weeks; and beta-blockers and central alpha-2 agonists for 1-2 weeks.
• Hypokalemia should be corrected before testing, as low potassium can suppress aldosterone production and lead to false negatives.
• The ARR is highly sensitive but has limited specificity, so positive results require confirmation with additional tests such as salt loading, captopril challenge, or fludrocortisone suppression tests.

Interpretation of ARR Results

• An ARR greater than 30 ng/dL per ng/mL/h (with aldosterone >10 ng/dL) is considered positive and suggestive of primary hyperaldosteronism, as stated in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.
• The ARR result should be interpreted in the context of the specific medication(s) the patient is taking, and input from a hypertension specialist or endocrinologist may be necessary.

Additional Testing and Diagnosis

• The diagnosis of primary aldosteronism generally requires a confirmatory test, such as an intravenous saline suppression test or oral salt-loading test, as recommended by the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1.
• If the diagnosis of primary aldosteronism is confirmed, the patient should be referred for an adrenal venous sampling procedure to determine whether the increased aldosterone production is unilateral or bilateral in origin.

From the Research

Diagnostic Tests for Primary Hyperaldosteronism

The diagnosis of primary hyperaldosteronism (primary aldosteronism) involves a series of tests to confirm the presence of autonomous aldosterone production. The following are some of the diagnostic tests used:

• Aldosterone-to-renin ratio (ARR): This is a widely used screening test for primary aldosteronism 2, 3, 4.
• Plasma aldosterone concentration (PAC) and plasma renin activity (PRA): These tests are used to screen for primary aldosteronism, with a PAC > or = 12.0 ng/dl and PRA < or = 1.0 ng/ml/h being proposed as initial screening criteria 2.
• ACTH stimulation test: This test is used as a secondary screening test for primary aldosteronism and has been shown to be the most sensitive and specific among several tests 2.
• Captopril suppression test, furosemide plus upright test: These tests are also used as secondary screening tests for primary aldosteronism, but have been shown to be less sensitive and specific than the ACTH stimulation test 2.
• Adrenal venous sampling: This is considered the gold standard method for defining the subtype of primary aldosteronism, but is not indicated in all cases 5, 6, 4.

Sensitivity of Diagnostic Tests

The sensitivity of the diagnostic tests for primary hyperaldosteronism varies:

• ARR: The sensitivity of the ARR has been reported to be low, with a sensitivity of 22.2% when using the recommended cut-off 3.
• PAC and PRA: The sensitivity and specificity of PAC and PRA have been reported to be higher than ARR, with ROC analysis showing that PAC and PRA are more sensitive and specific than ARR for PA screening 2.
• ACTH stimulation test: The ACTH stimulation test has been shown to be the most sensitive and specific among several tests, with a high sensitivity and specificity for primary aldosteronism 2.

Most Sensitive Diagnostic Test

Based on the available evidence, the ACTH stimulation test is the most sensitive diagnostic test for primary hyperaldosteronism, with a high sensitivity and specificity for the condition 2.