What is the diagnostic approach and treatment for primary aldosteronism?

Diagnostic Approach for Primary Aldosteronism

Who Should Be Screened

Screen all patients with resistant hypertension (BP uncontrolled on 3 medications including a diuretic), as primary aldosteronism is present in up to 20% of these individuals. 1, 2

Additional high-risk groups requiring screening include:

• Patients with severe hypertension (BP >180/110 mmHg) 2
• Hypokalemia (spontaneous or disproportionate to diuretic use) 1, 3
• Adrenal incidentaloma with hypertension 2, 3
• Family history of early-onset hypertension or stroke before age 40 2, 3
• Atrial fibrillation or obstructive sleep apnea with hypertension 3

Critical pitfall: Do not rely on hypokalemia as a screening criterion—it is absent in the majority of primary aldosteronism cases. 2

Initial Screening Test: Aldosterone-Renin Ratio (ARR)

Patient Preparation

Ensure patients are potassium-replete before testing, as hypokalemia suppresses aldosterone production and causes false-negative results. 1, 2

Medication management:

• Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks before testing 1, 2
• Stop beta-blockers, centrally acting drugs, and diuretics when feasible 2
• Use long-acting calcium channel blockers or alpha-receptor antagonists as alternatives during testing, as they minimally interfere with ARR 2
• If medications cannot be stopped, interpret results in the context of the specific medications the patient is taking 2

Collection Technique

Collect blood in the morning after the patient has been out of bed for 2 hours and seated for 5-15 minutes immediately before collection. 2

Interpretation of ARR

A positive screening test is defined as ARR ≥30 (when aldosterone is in ng/dL and renin activity in ng/mL/h) AND plasma aldosterone concentration ≥10 ng/dL. 1, 2

• The ARR cutoff of 30 has excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism 2
• Specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 2

Confirmatory Testing

A positive ARR requires confirmation with additional testing to demonstrate autonomous aldosterone secretion that cannot be suppressed. 1, 2, 3

Confirmatory test options:

• Intravenous saline suppression test: Administer IV saline and measure plasma aldosterone; failure to suppress confirms diagnosis 1, 3
• Oral sodium loading test: 24-hour urine aldosterone measurement after 3 days of high sodium intake 1, 2
• Captopril challenge test 3
• Fludrocortisone suppression test 2, 3

Perform confirmatory testing with unrestricted salt intake and normal serum potassium levels. 1, 2

Subtype Determination

Initial Imaging

After biochemical confirmation, obtain a non-contrast CT scan of the adrenal glands to exclude adrenocortical carcinoma and provide anatomic information. 2, 4

Critical warning: CT findings alone are insufficient for treatment decisions, as adenomas on imaging can represent hyperplasia, and false positives are common due to nodular hyperplasia. 2

Adrenal Venous Sampling (AVS)

Perform adrenal venous sampling to determine lateralization (unilateral vs. bilateral disease) before offering adrenalectomy. 1, 2, 4

• AVS is mandatory because up to 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone 2
• Exception: AVS may be omitted in patients <40 years with a single affected gland on imaging, as bilateral hyperplasia is rare in this population 2

Refer patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for AVS and subtype determination. 2, 3

Treatment Approach

Unilateral Disease (Aldosterone-Producing Adenoma)

Laparoscopic unilateral adrenalectomy is the treatment of choice for unilateral aldosterone production, improving BP in virtually 100% of patients and curing hypertension in approximately 50%. 1, 2

• Complete biochemical success is achieved in most patients 2
• Adrenalectomy normalizes hypokalemia in all patients 5
• Surgery resolves hypokalemia, lowers BP, reduces antihypertensive medication requirements, and improves cardiac and kidney function parameters 1

Bilateral Disease or Surgical Non-Candidates

Treat bilateral adrenal hyperplasia or patients unsuitable for surgery with mineralocorticoid receptor antagonists as the cornerstone of therapy. 2, 4

Medication Dosing

Spironolactone is the first-line medical treatment:

• Initial dose: 100-400 mg daily for primary hyperaldosteronism 6
• Use the lowest effective dosage determined for the individual patient for long-term maintenance 6

Eplerenone is an alternative option with fewer anti-androgenic side effects than spironolactone. 2

• Both adrenalectomy and medical therapy are effective in lowering BP and reversing left ventricular hypertrophy 1