How to manage hyperaldosteronism and associated hypertension?

Management of Hyperaldosteronism and Associated Hypertension

For patients with primary aldosteronism, treatment should be based on subtype determination, with mineralocorticoid receptor antagonists (such as spironolactone) as first-line therapy for bilateral disease and laparoscopic adrenalectomy for unilateral disease. 1

Diagnosis and Screening

Who to Screen

• Screen for primary aldosteronism in patients with:
  • Resistant hypertension
  • Hypokalemia (spontaneous or diuretic-induced)
  • Incidentally discovered adrenal mass
  • Family history of early-onset hypertension
  • Stroke at a young age (<40 years) 2, 1

Diagnostic Process

1. Initial Screening: Use plasma aldosterone-to-renin activity ratio (ARR)

   • Cutoff value: ARR > 30 with plasma aldosterone ≥ 10 ng/dL
   • Ensure unrestricted salt intake and normal potassium levels
   • Withdraw mineralocorticoid receptor antagonists for ≥4 weeks before testing 1

2. Confirmatory Testing:

   • Intravenous saline suppression test or oral salt-loading test 1

3. Subtype Determination:

   • Adrenal CT imaging
   • Adrenal venous sampling to determine if unilateral or bilateral 1

Treatment Algorithm

1. For Unilateral Disease (Aldosterone-Producing Adenoma)

• First-line: Laparoscopic adrenalectomy 1
  • Improves blood pressure in virtually 100% of patients
  • Completely cures hypertension in approximately 50% of patients

2. For Bilateral Disease (Idiopathic Hyperaldosteronism)

• First-line: Mineralocorticoid receptor antagonists 1

  • Spironolactone:

    • Starting dose: 12.5-25 mg daily
    • Titrate up to 50-100 mg daily (up to 200 mg if necessary) 1, 3
    • For primary hyperaldosteronism: 100-400 mg daily 3

  • Eplerenone (alternative with fewer sexual side effects):

    • Starting dose: 25 mg daily
    • Requires twice-daily dosing
    • Less potent than spironolactone 1

3. For Glucocorticoid-Remediable Aldosteronism (Type 1)

• Low-dose dexamethasone 1

Monitoring Protocol

Initial Monitoring

• Check serum potassium and renal function within 1-2 weeks of starting treatment
• Monitor potassium at 3 days and 1 week after initiating therapy
• Continue monthly monitoring for the first 3 months 1

Long-term Monitoring

• Regular assessment of blood pressure control
• Periodic measurement of serum potassium and renal function
• Watch for side effects:
  • Gynecomastia and breast tenderness in men
  • Menstrual irregularities in women
  • Sexual dysfunction
  • Hyperkalemia (especially with renal impairment) 1, 4

Efficacy and Benefits

• Spironolactone effectively controls blood pressure and hypokalemia in most cases 4
• In resistant hypertension, add-on spironolactone can decrease BP by 23.2/12.5 mmHg 5
• Particularly effective in patients with low serum potassium levels (<4 mmol/L) 5
• Effective even in patients without demonstrable hyperaldosteronism 6, 7

Managing Side Effects

• Common side effects of spironolactone:

  • Gynecomastia and breast tenderness in men
  • Decreased libido and impotence in men
  • Menstrual irregularities in women
  • Hyperkalemia 1, 4

• Strategies to minimize side effects:

  • Use lowest effective dose (ideally <150 mg/day) 8
  • Consider eplerenone for patients experiencing sexual side effects 1
  • Regular monitoring of potassium levels, especially when combined with ACE inhibitors 1

Special Considerations

• Early diagnosis and treatment are crucial as vascular remodeling from delayed diagnosis may result in residual hypertension even after treatment 1
• Bilateral adrenal hyperplasia accounts for approximately 60% of primary aldosteronism cases and requires lifelong medical therapy 1
• Spironolactone can be taken with or without food, but should be taken consistently with respect to food 3

Emerging Treatments

• Newer non-steroidal MRAs (finerenone, exarenone) and aldosterone synthase inhibitor (baxdrostat) are being investigated for primary aldosteronism 1