Primary Aldosteronism (PA)

Primary aldosteronism (PA) is an underdiagnosed cause of hypertension with significant cardiovascular, renal, and metabolic risk.³ Both the Endocrine Society and the American Heart Association (AHA) recommend screening hypertensive patients for PA.

According to the Endocrine Society’s 2025 Clinical Practice Guidelines, all patients with hypertension should be screened for PA.³

The AHA 2025 guidelines recommend screening for PA in patients with stage II or resistant hypertension an in patients with hypertension and enriching factors, such as spontaneous or diuretic-induced hypokalemia, muscle cramps/weakness, adrenal mass, sleep apnea, or family history of early hypertension or stroke.⁵

Previously, there were restrictions on timing, medication interference, sample collection, and patient preparation. The 2025 Endocrinology Society practice guidelines place a greater priority on ensuring that all patients with hypertension are screened for primary aldosteronism (PA) with minimal withdrawal or no withdrawal of interfering medication i.e. renin-angiotensin-aldosterone system inhibitors, diuretics, mineralocorticoid receptor antagonists (MRAs), or epithelial sodium channel inhibitors (ENaCs).³ Testing without changing medications can provide even greater confidence in the diagnosis, because most antihypertensive medications induce an increase in renin.

Medication withdrawal should be considered only if initial PA testing is normal yet clinical suspicion remains high and reducing interference may improve diagnostics clarity.

Discontinuation of any interfering medications should be based on the individual's safety and the feasibility of stopping the drug. As a temporary replacement, certain classes of medications can be administered, as they have minimal to no effect on the renin-angiotensin-aldosterone system (RAAS). These include calcium channel blockers, alpha-blockers, and hydralazine. Furthermore, it is crucial to assess potassium levels shortly before testing. Because low potassium decreases aldosterone release, it can potentially lead to a false-negative result.³

The guidelines recommend that patients with a diagnosis of primary aldosteronism should receive treatment specific to the condition. These treatment options include certain medications and surgery. Consult the full practice guidelines for more detailed information.³

Quest offers a stepwise testing pathway called the Plasma Renin Activity With Reflex to Aldosterone, which begins with testing plasma renin activity (PRA). If PRA is ≤1.00 ng/mL/hr, aldosterone levels are measured. The components of this reflex test can be ordered separately (Table below).

The full algorithm is depicted in this Figure and consistent with the Endocrine Society Clinical Practice Guidelines for Primary Aldosteronism.

The testing pathway is designed as a screening and reflexive interpretation test for primary aldosteronism (PA). Interpretation typically works as described below.

Plasma Renin Activity (PRA) >1.00 ng/mL/h is a negative screening result that suggests PA is unlikely:

• If a false negative is suspected based on medication use that raises PRA, consider retesting after withdrawing MRAs, epithelial sodium channel inhibitors (ENaCs), and diuretics for 4 weeks or angiotensin-converting enzyme inhibitors (ACEs) or angiotensin receptor blockers (ARBs) for 2 weeks.³

PRA ≤1.00 ng/mL/h, Plasma Aldosterone Concentration (PAC) ≥7.5 ng/dL, and Aldosterone Renin Ratio (ARR) >15.0 is a positive screening result that suggests PA is likely:

• Consider treatment or referral to a specialist.³
• If a false positive is suspected based on medication use that lowers PRA, consider retesting after withdrawing β-adrenergic blockers and centrally acting α2-agonists (eg, clonidine) for 2 weeks.³

PRA ≤1.00 ng/mL/h, PAC ≥7.5 ng/dL, and ARR ≤15.0 is a negative screening result that suggests PA is unlikely³:

• If a false negative is suspected based on a falsely low ARR, consider retesting after
  • Withdrawing MRAs or ENaCis for 4 weeks or ACEis or ARBs for 2 weeks (withdrawal should lower PRA and raise ARR).³
  • Ruling out or managing hypokalemia (Potassium, Serum, test code 733; normalizing potassium should raise PAC and raise ARR).³

PRA ≤1.00 ng/mL/h and PAC <7.5 ng/dL is a negative screening result that suggests PA is unlikely³:

• Low PRA with low PAC results mostly indicates low-renin hypertension and may indicate rare clinical scenarios or genetic conditions.⁶