What is primary hyperaldosteronism?

Primary Hyperaldosteronism: Definition, Diagnosis, and Management

Primary hyperaldosteronism is a group of disorders characterized by inappropriately high aldosterone production that is autonomous from the major regulators of secretion (angiotensin II and potassium) and cannot be suppressed with sodium loading. This condition causes hypertension, cardiovascular and kidney damage, sodium retention, suppressed plasma renin activity, and increased potassium excretion, which may lead to hypokalemia in severe cases. 1

Pathophysiology and Etiology

Primary hyperaldosteronism has two main subtypes:

• Unilateral aldosterone production (50% of cases)

  • Aldosterone-producing adenoma (most common)
  • Unilateral adrenal hyperplasia (rare)

• Bilateral adrenal hyperplasia (50% of cases)

  • Also known as idiopathic hyperaldosteronism 1

The excess aldosterone production leads to:

• Increased sodium reabsorption in the distal tubule
• Increased potassium and hydrogen ion excretion
• Volume expansion
• Hypertension that is often resistant to conventional treatment

Clinical Presentation

Primary hyperaldosteronism typically presents with:

• Hypertension (often resistant to conventional treatment)
• Hypokalemia (in severe cases, but absent in majority of patients)
• Muscle cramps or weakness (with hypokalemia)
• Metabolic alkalosis
• Arrhythmias, especially atrial fibrillation (with hypokalemia) 1

Screening Indications

Screening for primary hyperaldosteronism is recommended in patients with:

• Resistant hypertension
• Hypokalemia (spontaneous or substantial if diuretic-induced)
• Incidentally discovered adrenal mass
• Family history of early-onset hypertension
• Stroke at a young age (<40 years) 1

Diagnostic Approach

1. Screening Test:

   • Plasma aldosterone:renin activity ratio (ARR) is the most accurate and reliable screening method
   • Cutoff value is typically 30 when plasma aldosterone is reported in ng/dL and plasma renin activity in ng/mL/h
   • Plasma aldosterone concentration should be at least 10 ng/dL to interpret the test as positive 1

2. Test Conditions:

   • Unrestricted salt intake
   • Normal serum potassium
   • Withdrawal of mineralocorticoid receptor antagonists for at least 4 weeks 1

3. Confirmatory Testing:

   • Intravenous saline suppression test or
   • Oral salt-loading test with 24-hour urine aldosterone 1

4. Subtype Differentiation:

   • Adrenal CT scan
   • Adrenal venous sampling to determine unilateral vs. bilateral disease 1

Treatment

Treatment depends on the subtype:

For Unilateral Disease:

• Laparoscopic unilateral adrenalectomy:
  • Improves blood pressure in virtually 100% of patients
  • Results in complete cure of hypertension in about 50% of patients 1

For Bilateral Disease or Patients Unable to Undergo Surgery:

• Mineralocorticoid receptor antagonists:
  • Spironolactone (100-400 mg daily)
  • Eplerenone as an alternative 1, 2

Medication Management:

• For primary hyperaldosteronism treatment with spironolactone:
  • Initial dose: 100 mg daily (range 25-200 mg)
  • Maintenance dose: 100-400 mg daily
  • For long-term maintenance, use the lowest effective dose 2

Monitoring and Follow-up

• Regular monitoring of blood pressure
• Serum potassium levels
• Renal function
• Signs of cardiovascular damage

Prognosis and Outcomes

With appropriate treatment, primary hyperaldosteronism has excellent outcomes:

• Reduction in blood pressure
• Normalization of potassium levels
• Reversal of left ventricular hypertrophy
• Reduction in cardiovascular and renal complications 1, 3

Common Pitfalls to Avoid

1. Underdiagnosis: Primary hyperaldosteronism is often underdiagnosed because hypokalemia is absent in the majority of cases 1, 3

2. Inadequate screening: Failure to screen high-risk patients, particularly those with resistant hypertension

3. Improper testing conditions: Not normalizing potassium or discontinuing interfering medications before testing

4. Bypassing adrenal venous sampling: This is crucial for accurate subtype differentiation in most cases 4

5. Inadequate follow-up: After treatment, patients still require monitoring for blood pressure control and electrolyte balance

Early diagnosis and appropriate treatment of primary hyperaldosteronism are crucial to mitigate aldosterone-specific target organ damage and improve patient outcomes.