When should patients be tested for primary hyperaldosteronism?

When to Test for Primary Hyperaldosteronism

Screen all hypertensive patients who have resistant hypertension, hypokalemia (spontaneous or diuretic-induced), an incidentally discovered adrenal mass, family history of early-onset hypertension, or stroke before age 40 years. 1

High-Risk Populations Requiring Screening

The 2024 ESC Guidelines and 2017 ACC/AHA Guidelines provide clear Class I recommendations for screening specific patient groups:

Mandatory Screening Indications

• Resistant hypertension: Blood pressure >140/90 mmHg despite three antihypertensive medications including a diuretic, or requiring four or more drug classes 1

  • Primary aldosteronism prevalence reaches 11-20% in this population 1, 2

• Hypokalemia: Either spontaneous (unprovoked) or substantial if diuretic-induced (potassium <3.6 mmol/L, or <3.9 mmol/L on ACE inhibitors) 1, 3

  • Critical caveat: Hypokalemia is absent in the majority (>50%) of primary aldosteronism cases, so normal potassium does NOT exclude the diagnosis 1

• Incidentally discovered adrenal mass on CT or MRI performed for other reasons 1

• Family history of early-onset hypertension or stroke at young age (<40 years): Suggests possible glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type-1) 1

Additional High-Yield Screening Scenarios

• Severe hypertension: Blood pressure >180/110 mmHg, where prevalence can reach 12% 1

• Young-onset hypertension: Particularly severe hypertension before age 40, especially in women 3

Screening Test Methodology

Use the plasma aldosterone-to-renin ratio (ARR) as the screening test of choice 1

Practical Testing Approaches

The 2024 ESC Guidelines acknowledge two pragmatic strategies 1:

Option 1 - Test Without Medication Changes (Preferred for efficiency):

• Perform ARR testing while patients continue their current antihypertensive medications 1, 4
• Interpret results in context of medications being taken
• Advantage: Reduces barriers to screening and avoids dangerous blood pressure fluctuations 1
• Disadvantage: Requires specialist input for interpretation 1
• Studies confirm this approach is valid and does not require discontinuing medications 4

Option 2 - Optimize Medications Before Testing (For "clean" results):

• Discontinue interfering drugs when feasible: beta-blockers, centrally acting agents (clonidine, methyldopa), and diuretics 1
• Continue non-interfering medications: long-acting calcium channel blockers (dihydropyridine or non-dihydropyridine) and alpha-receptor antagonists 1
• Important exception: Mineralocorticoid receptor antagonists can be continued if stopping them poses safety risks (severe hypokalemia or severe hypertension), as recent evidence shows minimal impact on ARR accuracy in florid primary aldosteronism 1

ARR Interpretation

• Most commonly used cutoff: ARR >30 (when aldosterone in ng/dL and renin activity in ng/mL/h) 1
• Alternative cutoff: ARR >65.16 with aldosterone >416 pmol/L 2
• ARR >100 (ng/dL / ng/mL/h) also used in some protocols 4
• Critical point: Assess sodium intake (preferably 24-hour urinary sodium) and menstrual cycle timing in females for proper interpretation 1

Post-Screening Management

Refer all patients with positive screening tests to a hypertension specialist or endocrinologist for confirmatory testing and treatment 1

Why Referral Matters

• Confirmatory testing (saline suppression, fludrocortisone suppression) is required after positive screening 2
• Subtype determination via adrenal vein sampling is crucial to distinguish unilateral (surgical) from bilateral (medical) disease 5
• Early diagnosis and treatment improve cure rates and prevent irreversible vascular remodeling 5

Clinical Context and Pitfalls

Underscreening is Epidemic

Despite clear guidelines, screening rates remain dismally low—only 2-4% of eligible patients with resistant hypertension and hypokalemia are actually tested 1, 6. Testing is associated with 4-fold higher rates of evidence-based MRA therapy and better long-term blood pressure control 6.

Common Misconceptions

• Myth: Primary aldosteronism always presents with hypokalemia

  • Reality: Over 50% of cases are normokalemic 1, 3

• Myth: Medications must be stopped before screening

  • Reality: ARR can be performed on medications with appropriate interpretation 1, 4

Cardiovascular Risk

Primary aldosteronism carries increased cardiovascular disease risk that may be partly independent of blood pressure elevation 1. The deleterious effects of aldosterone excess are often reversible with appropriate treatment (surgery or mineralocorticoid receptor antagonists) 1.