What is the management and treatment of primary hyperaldosteronism?

Management and Treatment of Primary Hyperaldosteronism

Laparoscopic unilateral adrenalectomy is the definitive treatment for unilateral disease (aldosterone-producing adenoma), achieving blood pressure improvement in virtually 100% of patients and complete hypertension cure in approximately 50%, while bilateral disease requires lifelong medical therapy with mineralocorticoid receptor antagonists, starting with spironolactone 100-400 mg daily. 1, 2

Treatment Algorithm Based on Disease Subtype

Unilateral Disease (Aldosterone-Producing Adenoma or Unilateral Hyperplasia)

Surgical Management:

• Laparoscopic unilateral adrenalectomy is the treatment of choice, reversing aldosterone-mediated target organ damage including left ventricular hypertrophy, microalbuminuria, and metabolic complications 1, 3, 4
• Surgery normalizes the renin-angiotensin-aldosterone system and potassium levels in all patients, with complete hypertension resolution in approximately 50% of cases 3
• For patients unsuitable for surgery, proceed to medical management as outlined below 2

Bilateral Disease (Idiopathic Hyperaldosteronism/Bilateral Adrenal Hyperplasia)

Medical Management - First-Line:

• Spironolactone is the preferred mineralocorticoid receptor antagonist, with FDA-approved dosing of 100-400 mg daily for primary aldosteronism 5, 1, 2
• Start at 100 mg daily (may range 25-200 mg) and titrate based on blood pressure and potassium response 2
• For patients with cirrhosis, initiate therapy in hospital setting with slow titration 2
• Administer for at least 5 days before dose escalation when used as sole diuretic 2

Medical Management - Alternative Agent:

• Eplerenone 50-100 mg daily (in 1-2 divided doses) is recommended for patients developing gynecomastia, breast tenderness, or sexual dysfunction on spironolactone, with equal blood pressure control efficacy 1

Additional Antihypertensive Therapy:

• If blood pressure remains uncontrolled on maximum mineralocorticoid receptor antagonist doses, add potassium-sparing diuretics (amiloride or triamterene) or calcium channel antagonists 6
• Doses exceeding 100 mg/day spironolactone generally provide no additional blood pressure reduction 2

Special Subtype: Familial Hyperaldosteronism Type 1

• Low-dose dexamethasone is the treatment of choice for glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type 1) 1

Critical Safety Monitoring Protocol

Pre-Treatment Requirements:

• Verify serum potassium ≤5.0 mEq/L before initiating any aldosterone antagonist 1
• Confirm serum creatinine <2.0-2.5 mg/dL or eGFR >30 mL/min 1
• Discontinue all potassium supplements prior to starting mineralocorticoid receptor antagonists 1

Monitoring Schedule:

• Check potassium and creatinine at 3 days, 1 week, then monthly for first 3 months 1
• After stabilization, monitor every 3 months indefinitely 1
• Closely monitor serum electrolytes and renal function at treatment initiation 6

Critical Contraindications and Drug Interactions

Absolute Avoidance:

• Never combine mineralocorticoid receptor antagonists with potassium supplements or potassium-sparing diuretics due to severe hyperkalemia risk 1
• Do not combine with NSAIDs or COX-2 inhibitors due to increased hyperkalemia and renal dysfunction risk 1

Requires Intensive Monitoring:

• Use extreme caution combining mineralocorticoid receptor antagonists with ACE inhibitors or ARBs, requiring close potassium monitoring 1
• Use mineralocorticoid receptor antagonists cautiously in patients with eGFR <45 mL/min 1

Common Pitfalls to Avoid

Diagnostic Pitfalls:

• Hypokalemia is absent in the majority of primary aldosteronism cases and has low negative predictive value for diagnosis - do not exclude primary aldosteronism based on normal potassium 5, 1
• Adrenal vein sampling should be performed in specialized centers for accurate subtype determination before surgical decisions 1

Treatment Pitfalls:

• Delayed diagnosis and treatment leads to irreversible vascular remodeling, resulting in persistent hypertension even after appropriate treatment 1, 3
• Early diagnosis and treatment are essential to prevent irreversible target organ damage including cardiovascular and renal complications 1, 4
• Failure to refer complex cases to hypertension specialists or endocrinologists delays optimal management 5

Screening Indications

The American College of Cardiology recommends screening with plasma aldosterone-to-renin ratio in patients with: 5

• Resistant hypertension
• Spontaneous or substantial diuretic-induced hypokalemia
• Incidentally discovered adrenal mass
• Family history of early-onset hypertension
• Stroke at young age (<40 years)

Treatment Goals

The primary objectives are normalizing blood pressure, eliminating excessive aldosterone production, reducing associated comorbidities, improving quality of life, and reducing mortality through targeted aldosterone-specific interventions 4, 7