What is the initial treatment for hypertension related to aldosterone imbalance?

Initial Treatment for Hypertension Related to Aldosterone Imbalance

For unilateral primary aldosteronism, laparoscopic adrenalectomy is the definitive treatment of choice, while bilateral disease requires medical therapy with mineralocorticoid receptor antagonists (MRAs), specifically spironolactone as first-line treatment. 1

Treatment Algorithm Based on Disease Subtype

Step 1: Determine Lateralization

• Adrenal vein sampling is essential to distinguish unilateral from bilateral aldosterone production before selecting treatment, as this determines whether surgical or medical management is appropriate 1
• Approximately 50% of primary aldosteronism cases are unilateral (typically aldosterone-producing adenoma) and 50% are bilateral (idiopathic hyperaldosteronism) 1, 2

Step 2: Unilateral Disease (Surgical Approach)

• Unilateral laparoscopic adrenalectomy improves blood pressure in virtually 100% of patients and achieves complete cure of hypertension in approximately 50% of cases 2, 3
• Surgery reverses aldosterone-induced cardiovascular and kidney damage 1
• For patients who are poor surgical candidates due to age or comorbidities, proceed to medical therapy instead 1

Step 3: Bilateral Disease or Non-Surgical Candidates (Medical Approach)

• Start spironolactone 50-100 mg once daily as first-line treatment 1, 2, 4
• Titrate up to 300-400 mg daily if necessary to achieve blood pressure control 1, 2, 4
• Eplerenone is an alternative MRA (50-100 mg daily in 1-2 divided doses) with fewer sexual side effects than spironolactone, though it is less potent and requires twice-daily dosing 1, 3, 5

Medication Dosing Specifics

Spironolactone Dosing

• Initial dose: 25-100 mg once daily for hypertension 4
• For primary aldosteronism specifically: 100-400 mg daily for long-term maintenance 4
• Can be taken with or without food, but maintain consistency 4

Eplerenone Dosing

• Starting dose: 50 mg once or twice daily 5, 6
• Maximum dose: 100 mg daily 5
• Reaches steady state within 2 days 5

Critical Monitoring Requirements

Electrolyte and Renal Function Surveillance

• Monitor serum potassium and creatinine closely when initiating MRA therapy 2, 6
• Risk of hyperkalemia is increased, particularly in elderly patients (≥65 years) and those with reduced kidney function 3, 5
• Use MRAs with extreme caution if eGFR <45 mL/min 3

Combination Therapy Considerations

• Combining MRAs with thiazide diuretics (e.g., hydrochlorothiazide or chlorthalidone) maximizes efficacy and reduces hyperkalemia risk in resistant hypertension 7
• Avoid combining MRAs with ACE inhibitors, ARBs, or potassium supplements without careful monitoring due to severe hyperkalemia risk 3, 7

Special Populations and Rare Forms

Familial Hyperaldosteronism Type 1

• Low-dose dexamethasone is the specific treatment for glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type 1) 1, 2, 3
• This form can be safely treated during pregnancy with dexamethasone 1
• Requires genetic testing for germ-line mutations to diagnose 1

Common Pitfalls to Avoid

Diagnostic Errors

• Do not exclude primary aldosteronism based on normal potassium levels alone—hypokalemia is absent in the majority of cases and has low negative predictive value 1, 3
• Ensure proper screening test preparation: patients need unrestricted salt intake, normal serum potassium, and MRAs withdrawn for at least 4 weeks before aldosterone:renin ratio testing 1

Treatment Timing

• Early diagnosis and treatment are critical—delayed diagnosis leads to irreversible vascular remodeling that causes residual hypertension even after appropriate treatment 1, 2, 3
• Vascular remodeling affects renal function and accounts for why some patients have persistent hypertension despite removing the aldosterone source 1

Medication Safety

• Never use eplerenone with strong CYP3A4 inhibitors (e.g., ketoconazole, saquinavir) as they significantly increase eplerenone blood levels 5
• Spironolactone causes gynaecomastia and erectile dysfunction in men more frequently than eplerenone 1

Emerging Therapies

• Newer non-steroidal MRAs (finerenone, exarenone) and aldosterone synthase inhibitors (baxdrostat) are being tested for primary aldosteronism and show promise in resistant hypertension 1, 2

Referral Indications

• Refer to hypertension specialist or endocrinologist after positive screening test for further evaluation, confirmatory testing, and subtype determination 1
• Complex cases and rare forms of secondary hypertension should be managed at specialized hypertension centers 1, 2