What are the initial steps and treatment options for primary hyperaldosteronism?

Management of Primary Hyperaldosteronism

The management of primary hyperaldosteronism requires proper diagnosis followed by targeted treatment based on whether the condition is unilateral or bilateral, with mineralocorticoid receptor antagonists for bilateral disease and laparoscopic adrenalectomy for unilateral disease. 1

Initial Diagnostic Steps

Screening

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

Laboratory Testing

1. Aldosterone-to-Renin Ratio (ARR):

   • Primary screening test with high negative predictive value 2
   • ARR >30 with plasma aldosterone ≥10 ng/dL is suggestive 1
   • Ensure patient has:
     • Unrestricted salt intake
     • Normal serum potassium
     • Mineralocorticoid receptor antagonists withdrawn for ≥4 weeks 1

2. Confirmatory Testing:

   • Required if ARR is elevated
   • Options include:
     • Intravenous saline suppression test
     • Oral salt-loading test 1

Imaging and Subtype Determination

1. Adrenal CT Imaging:

   • Initial study to identify potential adenomas and exclude adrenocortical carcinoma 1

2. Adrenal Venous Sampling:

   • Critical for determining if aldosterone production is unilateral or bilateral
   • Essential for guiding appropriate treatment approach 1

Treatment Algorithm

For Bilateral Disease (Idiopathic Hyperaldosteronism)

1. First-line Treatment: Mineralocorticoid receptor antagonists (MRAs)

   • Spironolactone:

     • Starting dose: 12.5-25 mg daily
     • Titrate up to 50-100 mg daily (maximum 200 mg if necessary) 1
     • FDA-approved for long-term maintenance therapy for bilateral micro or macronodular adrenal hyperplasia 3

   • Eplerenone (alternative with fewer sexual side effects):

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

2. Monitoring:

   • Check serum potassium and renal function within 1-2 weeks of starting treatment
   • Monitor for hyperkalemia, especially when combined with ACE inhibitors
   • Potassium monitoring: 3 days and 1 week after initiating therapy, then monthly for first 3 months 1

For Unilateral Disease (Aldosterone-Producing Adenoma)

1. First-line Treatment: Laparoscopic adrenalectomy

   • Improves blood pressure in virtually 100% of patients
   • Completely cures hypertension in approximately 50% of patients 1

2. Preoperative Management:

   • Spironolactone 100-400 mg daily in preparation for surgery 3

3. Alternative for Non-surgical Candidates:

   • Long-term maintenance therapy with spironolactone at lowest effective dosage 3

Special Considerations

Side Effects of MRAs

• Gynecomastia and breast tenderness in men
• Menstrual irregularities in women
• Sexual dysfunction
• Hyperkalemia (especially in patients with renal impairment) 1

Treatment Outcomes

• Early diagnosis and treatment mitigate aldosterone-specific target organ damage 4
• Vascular remodeling from delayed diagnosis may result in residual hypertension even after treatment 1

Common Pitfalls to Avoid

1. Delayed Diagnosis: Primary aldosteronism is underdiagnosed because it lacks specific, easily identifiable features 4

2. Medication Interference with ARR Testing:

   • Mineralocorticoid receptor antagonists raise aldosterone levels
   • Direct renin inhibitors and β-blockers lower renin levels 2

3. Inadequate Subtype Determination:

   • Failing to perform adrenal venous sampling when indicated can lead to inappropriate treatment selection 1

4. Insufficient Monitoring:

   • Inadequate potassium monitoring can lead to dangerous hyperkalemia, especially when MRAs are combined with ACE inhibitors 1

Primary aldosteronism is a common and potentially curable form of hypertension that requires systematic evaluation and targeted treatment to reduce cardiovascular morbidity and mortality.