From the Guidelines
An abnormally elevated plasma aldosterone concentration (PAC) is typically considered to be >15 ng/dL (>416 pmol/L), while an elevated aldosterone-to-renin ratio (ARR) is generally defined as >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). The ARR is the preferred initial screening test for primary aldosteronism, as it accounts for both aldosterone levels and renin activity, 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. An elevated ARR suggests inappropriate aldosterone production relative to the renin-angiotensin system status.
Key Considerations
- The plasma aldosterone concentration should be at least 10 ng/dL to interpret the test as positive, as noted in the guideline 1.
- Patients should have unrestricted salt intake, serum potassium in the normal range, and mineralocorticoid receptor antagonists (e.g., spironolactone or eplerenone) withdrawn for at least 4 weeks before testing 1.
- Antihypertensives like beta-blockers, ACE inhibitors, ARBs, and diuretics should ideally be discontinued for 2-4 weeks before testing.
- Hypokalemia should be corrected, and patients should maintain a normal sodium diet.
- Morning blood sampling is preferred with the patient in a seated position for at least 5-15 minutes.
Additional Testing
A positive screening test requires confirmation with additional tests such as salt loading, captopril challenge, or fludrocortisone suppression test before proceeding to adrenal imaging and adrenal vein sampling, as recommended in the guideline 1. If the diagnosis of primary aldosteronism is confirmed, the patient is referred for an adrenal venous sampling procedure to determine whether the increased aldosterone production is unilateral or bilateral in origin.
Treatment
If unilateral aldosterone production is documented on adrenal venous sampling, the patient is referred for unilateral laparoscopic adrenalectomy, which improves BP in virtually 100% of patients and results in a complete cure of hypertension in about 50% 1. If the patient has bilaterally increased aldosterone secretion on adrenal venous sampling or has a unilateral source of excess aldosterone production but cannot undergo surgery, the patient is treated with spironolactone or eplerenone as agent of choice 1.
From the Research
Definition of Abnormally Elevated PAC or ARR
An abnormally elevated plasma aldosterone concentration (PAC) or aldosterone-renin ratio (ARR) is a key indicator of primary aldosteronism (PA) 2, 3, 4, 5, 6.
Criteria for Elevated PAC or ARR
The criteria for an elevated PAC or ARR vary, but a commonly used threshold is an ARR greater than 30 3.
Diagnostic Process
The diagnostic process for primary aldosteronism typically involves:
- Initial case detection using the plasma aldosterone concentration to plasma renin activity ratio (PAC/PRA) or ARR 4, 6
- Confirmatory testing, such as the captopril challenge, oral or intravenous salt loading, or fludrocortisone suppression, to confirm autonomous aldosterone production 3, 4, 6
- Adrenal computed tomography and adrenal vein sampling to differentiate unilateral from bilateral adrenal production of aldosterone 3, 5, 6
Treatment Options
Treatment options for primary aldosteronism depend on the subtype and may include: