What is primary aldosteronism?

Primary Aldosteronism: Definition and Management

Primary aldosteronism is a group of disorders characterized by inappropriately high aldosterone production that is relatively autonomous from the major regulators of secretion (angiotensin II and potassium) and cannot be suppressed with sodium loading. 1

Pathophysiology

Primary aldosteronism causes:

• Hypertension
• Cardiovascular and kidney damage
• Sodium retention
• Suppressed plasma renin activity
• Increased potassium excretion (which may lead to hypokalemia)

The condition is characterized by two main subtypes:

• Unilateral aldosterone production (approximately 50% of cases)
  • Usually aldosterone-producing adenoma
  • Rarely unilateral adrenal hyperplasia
• Bilateral adrenal hyperplasia (approximately 50% of cases)
  • Also called idiopathic hyperaldosteronism 1

Clinical Presentation

Patients with primary aldosteronism may present with:

• Resistant hypertension
• Hypokalemia (spontaneous or diuretic-induced) - though notably absent in the majority of cases
• Muscle cramps or weakness
• Incidentally discovered adrenal mass
• Family history of early-onset hypertension
• Stroke at a young age (<40 years) 1

It's important to note that hypokalemia, once considered a hallmark of primary aldosteronism, is actually absent in the majority of cases and has a low negative predictive value for diagnosis 1.

Screening Recommendations

The ACC/AHA guidelines recommend screening for primary aldosteronism in adults with hypertension who have any of the following:

• 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. Initial screening: Plasma aldosterone-to-renin activity ratio (ARR)

   • Most accurate and reliable screening test
   • Common cutoff value is 30 (when plasma aldosterone is in ng/dL and renin activity in ng/mL/h)
   • Plasma aldosterone should be at least 10 ng/dL for a positive test
   • Patients should have unrestricted salt intake, normal serum potassium, and mineralocorticoid receptor antagonists withdrawn for at least 4 weeks before testing 1

2. Confirmatory testing if screening is positive:

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

3. Subtype differentiation if confirmed:

   • CT imaging of adrenal glands
   • Adrenal venous sampling to determine unilateral vs. bilateral disease 1

Treatment Approaches

Treatment depends on the subtype:

For Unilateral Disease:

• Unilateral laparoscopic adrenalectomy
  • Improves blood pressure in virtually 100% of patients
  • Complete cure of hypertension in about 50% of patients 1

For Bilateral Disease or Non-surgical Candidates:

• Mineralocorticoid receptor antagonists
  • Spironolactone (first-line) or eplerenone
  • Dosage: 100-400 mg daily for spironolactone 2
  • These medications effectively block the toxic effects of aldosterone on tissues 3

Clinical Pearls and Pitfalls

1. Don't rely on hypokalemia for diagnosis: Most patients with primary aldosteronism are normokalemic 1, 3.

2. Proper preparation for ARR testing: Ensure normal potassium levels and discontinue mineralocorticoid receptor antagonists for 4-6 weeks before testing 1.

3. Adrenal venous sampling: This is the most accurate method for distinguishing between unilateral and bilateral disease when surgical treatment is considered 3.

4. Medication management: When using spironolactone, be aware that it can be taken with or without food, but should be taken consistently with respect to food intake 2.

5. Long-term follow-up: Even after successful treatment, patients should be monitored for persistent hypertension, as surgery may not completely cure hypertension in all cases 1.

Primary aldosteronism is more common than previously thought and represents an important, potentially curable or effectively treatable cause of secondary hypertension. Early diagnosis and appropriate treatment can significantly reduce cardiovascular and renal complications associated with this condition.