What is the initial treatment for primary aldosteronism?

Initial Treatment for Primary Aldosteronism

The initial treatment for primary aldosteronism depends critically on whether the disease is unilateral or bilateral: laparoscopic unilateral adrenalectomy is the definitive treatment for unilateral disease (aldosterone-producing adenoma or unilateral hyperplasia), while mineralocorticoid receptor antagonists—specifically spironolactone—are the first-line treatment for bilateral disease (idiopathic hyperaldosteronism). 1, 2, 3

Treatment Algorithm Based on Disease Subtype

Step 1: Determine Lateralization

• Adrenal venous sampling (AVS) is mandatory before proceeding to surgery to distinguish unilateral from bilateral disease, as CT imaging alone is insufficient—up to 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone 3, 4
• The only exception is patients under 40 years of age with a single adenoma on imaging, as bilateral hyperplasia is rare in this population 4

Step 2A: Unilateral Disease (Aldosterone-Producing Adenoma or Unilateral Hyperplasia)

• Laparoscopic unilateral adrenalectomy is the treatment of choice, improving blood pressure in virtually 100% of patients and achieving complete cure of hypertension in approximately 50% of cases 1, 2, 3
• Surgery normalizes hypokalemia, reduces antihypertensive medication requirements, and reverses aldosterone-induced target organ damage including cardiac and renal complications 3, 4
• Patients should undergo surgery at specialized centers with expertise in adrenal surgery 2, 4

Step 2B: Bilateral Disease (Idiopathic Hyperaldosteronism)

• Spironolactone is the first-line medical treatment, with an initial dose of 50-100 mg daily (FDA-approved dosing range 100-400 mg/day for primary aldosteronism) 2, 3, 5
• The starting dose should be 25 mg once daily in patients with reduced kidney function (eGFR 30-50 mL/min/1.73 m²) due to hyperkalemia risk 5
• Titrate spironolactone up to 300-400 mg/day if needed to achieve blood pressure control and correct hypokalemia 2, 6

Step 2C: Alternative Medical Therapy

• Eplerenone (50-100 mg daily in 1-2 doses) is the preferred alternative for patients who develop gynecomastia, breast tenderness, erectile dysfunction, or menstrual irregularities on spironolactone 3, 7
• Eplerenone has equal effectiveness to spironolactone for blood pressure control but with fewer anti-androgenic side effects due to its selective mineralocorticoid receptor antagonism 3, 7

Critical Safety Monitoring

Before Initiating Mineralocorticoid Receptor Antagonists

• Verify serum potassium ≤5.0 mEq/L and confirm serum creatinine <2.0-2.5 mg/dL or eGFR >30 mL/min before starting therapy 3
• Discontinue all potassium supplements prior to initiation 3
• Ensure patients are potassium-replete, as hypokalemia should be corrected before starting treatment 4

During Treatment Monitoring

• Check potassium and creatinine at 3 days, 1 week, then monthly for the first 3 months, and subsequently every 3 months if stable 3
• Close monitoring of serum electrolytes and renal function is essential when initiating treatment 2, 6

Common Pitfalls and Contraindications

Medication Interactions to Avoid

• Never combine mineralocorticoid receptor antagonists with potassium supplements or potassium-sparing diuretics due to severe hyperkalemia risk 3
• Avoid combining with ACE inhibitors or ARBs without extremely close monitoring due to additive hyperkalemia risk 3
• Do not use with NSAIDs or COX-2 inhibitors as they increase risk of hyperkalemia and renal dysfunction 3

Surgical Considerations

• Do not proceed to adrenalectomy based on imaging alone—AVS is required for definitive lateralization except in the specific exception noted above 3, 4
• Patients unsuitable for surgery (due to comorbidities or patient preference) should receive long-term maintenance therapy with mineralocorticoid receptor antagonists at the lowest effective dose 5

Special Populations

Familial Hyperaldosteronism Type 1 (Glucocorticoid-Remediable Aldosteronism)

• Low-dose dexamethasone is the specific treatment for this rare familial form, which can be identified through genetic testing 2, 3

Patients with Renal Impairment

• Use mineralocorticoid receptor antagonists with extreme caution in patients with eGFR <45 mL/min due to significantly increased hyperkalemia risk 3
• Consider initiating at 25 mg every other day in patients with eGFR 30-50 mL/min/1.73 m² 5

Importance of Early Diagnosis and Treatment

• Delayed diagnosis leads to irreversible vascular remodeling, resulting in persistent hypertension even after appropriate treatment 2, 3
• Early treatment reverses aldosterone-specific cardiovascular and renal damage, improving quality of life and reducing mortality 8, 9
• Primary aldosteronism causes excess cardiovascular morbidity beyond that explained by blood pressure elevation alone, making targeted treatment essential 8, 9