What is the recommended management for primary hyperaldosteronism when adrenal vein sampling shows no lateralisation (bilateral disease)?

Management of Primary Hyperaldosteronism with Bilateral Disease (No Lateralization on AVS)

When adrenal vein sampling shows no lateralization (bilateral adrenal hyperplasia), medical management with mineralocorticoid receptor antagonists—specifically spironolactone or eplerenone—is the treatment of choice, as surgery is not indicated for bilateral disease. 1, 2

Medical Management Algorithm

First-Line Therapy: Mineralocorticoid Receptor Antagonists

Spironolactone is the primary agent:

• Start at 100-400 mg daily for primary hyperaldosteronism with bilateral disease 3
• Alternative starting approach: Begin at 12.5-25 mg/day and titrate up to 100 mg/day based on blood pressure and potassium response 4
• FDA-approved specifically for long-term maintenance therapy in patients with bilateral micro or macronodular adrenal hyperplasia (idiopathic hyperaldosteronism) 3

Eplerenone as alternative:

• Use 50-100 mg/day if spironolactone is not tolerated 4
• Consider in patients who experience gynecomastia or other anti-androgenic side effects from spironolactone 1

Monitoring Requirements

Close biochemical surveillance is essential:

• Monitor serum electrolytes and creatinine closely after initiating therapy 4
• Watch for hyperkalemia, particularly in patients with eGFR 30-50 mL/min/1.73 m² 3
• Assess blood pressure response at two-week intervals 3
• Annual follow-up should include assessment of health status, weight, blood pressure, and serum electrolytes 2

Second-Line and Adjunctive Therapy

If blood pressure remains uncontrolled on mineralocorticoid receptor antagonists alone:

• Add potassium-sparing diuretics (amiloride or triamterene) 4
• Consider calcium channel antagonists as additional agents 4
• Doses greater than 100 mg/day of spironolactone generally do not provide additional blood pressure reductions 3

Why Surgery Is Not Indicated

The distinction between unilateral and bilateral disease is crucial for treatment decisions:

• Unilateral adrenalectomy improves blood pressure in virtually 100% of patients with unilateral disease and cures hypertension in approximately 50% 1, 2
• However, bilateral disease requires both adrenal glands for aldosterone production, making unilateral surgery ineffective 5
• Bilateral adrenalectomy would necessitate lifelong glucocorticoid and mineralocorticoid replacement, creating more morbidity than medical management 2

Critical Pitfalls to Avoid

Do not rely on CT imaging alone to determine lateralization:

• CT scanning clearly localizes adenomas in only 50% of histologically proven cases 6
• Approximately 10% of people over age 35 have nonfunctioning adrenal incidentalomas regardless of hypertension status 7
• AVS results alter management in approximately 35.7% of patients who would have been treated improperly based on imaging alone 2
• 25% of patients would have had unnecessary adrenalectomy based on CT findings alone 2

Ensure proper AVS technique was used:

• Cortisol measurement in catheterization samples confirms proper catheter placement 2, 8
• Mineralocorticoid receptor antagonists must be withdrawn for at least 4 weeks before AVS testing 1
• Serum potassium should be normalized and patients should have unrestricted salt intake prior to the procedure 1

Expected Outcomes with Medical Management

Both adrenalectomy (for unilateral disease) and medical therapy (for bilateral disease) are effective:

• Medical management effectively lowers blood pressure and reverses left ventricular hypertrophy 1
• Biochemical control (normalization of aldosterone-renin ratio) should be the primary endpoint, not just blood pressure normalization 5
• Chronically elevated aldosterone leads to cardiovascular complications independent of blood pressure levels 5

Long-term maintenance therapy with spironolactone or eplerenone is appropriate for patients with bilateral disease who are not surgical candidates. 3