When should patients with hypertension be screened for primary aldosteronism?

When to Screen for Primary Aldosteronism

Screen all patients with resistant hypertension (blood pressure >140/90 mmHg on three or more medications including a diuretic), as primary aldosteronism affects up to 20% of this population and represents a potentially curable cause of hypertension with dramatically higher cardiovascular risk than essential hypertension. 1, 2, 3

Mandatory Screening Indications

The following patients must be screened for primary aldosteronism:

• Resistant hypertension: Blood pressure remains >140/90 mmHg despite optimal doses of three or more antihypertensive medications including a diuretic, or requires four or more drug classes 1, 3
• Hypokalemia: Either spontaneous or diuretic-induced (substantial), though notably absent in approximately 50% of primary aldosteronism cases 1, 2, 3
• Adrenal incidentaloma: Any incidentally discovered adrenal mass on CT or MRI performed for other reasons 1, 2, 3
• Family history: Early-onset hypertension or stroke at young age (<40 years) in first-degree relatives, suggesting possible familial hyperaldosteronism 1, 2, 3
• Young-onset hypertension: Patients <30-40 years of age with hypertension, particularly without traditional risk factors like obesity or metabolic syndrome 1, 4

Strongly Recommended Screening Situations

Beyond the mandatory indications, screening should be strongly considered in:

• Severe hypertension: Blood pressure >180/110 mmHg 1, 2
• Sudden deterioration in blood pressure control in previously well-controlled patients 1
• Hypertensive urgency or emergency 1
• Early target organ damage: Stroke, atrial fibrillation unexplained by structural heart disease, or other cardiovascular complications at young age 4
• Obstructive sleep apnea with hypertension 4

Critical Clinical Context

Why This Matters

Primary aldosteronism is not merely elevated blood pressure—it carries dramatically worse cardiovascular outcomes than essential hypertension at equivalent blood pressure levels, including 3.7-fold increased heart failure, 4.2-fold increased stroke, 6.5-fold increased myocardial infarction, and 12.1-fold increased atrial fibrillation 2. These effects are often reversible with appropriate treatment (surgery or mineralocorticoid receptor antagonists) 3.

Common Pitfalls to Avoid

Never rely on the presence or absence of hypokalemia alone to decide whether to screen—hypokalemia is absent in >50% of confirmed primary aldosteronism cases 1, 2, 3. This is the most common reason for missed diagnoses.

Do not assume normal-appearing adrenal glands on imaging exclude the diagnosis—CT scan is frequently normal in primary aldosteronism 5.

Recognize that only 2.1% of eligible patients actually get screened despite guideline recommendations, representing a massive gap in care 6. The low screening rate is not due to medication interference but rather lack of awareness 6.

Screening Test Methodology

Use the plasma aldosterone-to-renin ratio (ARR) as the screening test 1, 2, 3. A positive screen requires:

• ARR ≥20-30 (when aldosterone in ng/dL and renin activity in ng/mL/h) AND
• Plasma aldosterone concentration ≥10-15 ng/dL 1, 2, 3

Patient preparation: Ensure potassium repletion before testing (hypokalemia suppresses aldosterone production causing false-negatives), collect blood in the morning after patient has been out of bed for 2 hours and seated for 5-15 minutes 2, 3. Ideally discontinue interfering medications (beta-blockers, diuretics, ACE inhibitors/ARBs) when clinically feasible, though the 2024 guidelines acknowledge testing on current medications is pragmatically acceptable 3.

Next Steps After Positive Screening

All positive screening tests require confirmatory testing (intravenous saline suppression test or oral sodium loading with 24-hour urine aldosterone) to demonstrate autonomous aldosterone secretion 1, 2, 3. Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination via adrenal venous sampling, which is mandatory before offering adrenalectomy to distinguish unilateral (surgical) from bilateral (medical) disease 1, 2, 3.

Real-World Application

In resistant hypertension specifically, consider starting spironolactone 25-50 mg daily immediately after positive ARR screening even before confirmatory testing is completed, as it provides significant additional blood pressure reduction of 25/12 mmHg and benefits patients regardless of whether formal primary aldosteronism is ultimately confirmed 2. Monitor serum potassium within 1 week of initiation, particularly in older patients, those with diabetes, chronic kidney disease, or concomitant use of ACE inhibitors/ARBs 2.