Management of Aldosterone Dysregulation
The management of aldosterone dysregulation primarily involves mineralocorticoid receptor antagonists (spironolactone or eplerenone) for bilateral disease and laparoscopic adrenalectomy for unilateral disease, with treatment decisions guided by proper diagnostic workup including adrenal venous sampling. 1, 2, 3
Diagnostic Approach
Screening
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 young age (<40 years) 1
Use plasma aldosterone-to-renin ratio (ARR) as the primary screening test
Confirmation
- Perform confirmatory testing with either:
Subtype Determination
- Adrenal CT imaging as initial study
- Adrenal venous sampling to definitively determine if aldosterone production is unilateral or bilateral 1, 2
- Critical for guiding treatment approach
- Should be performed by experienced radiologists
Treatment Algorithm
1. Unilateral Aldosterone-Producing Adenoma
- First-line treatment: Laparoscopic adrenalectomy 1, 2, 3
- Improves BP in virtually 100% of patients
- Completely cures hypertension in ~50% of patients
- Resolves hypokalemia and improves cardiac and kidney function
2. Bilateral Adrenal Hyperplasia
First-line treatment: Mineralocorticoid receptor antagonists 1, 2, 3
a) Spironolactone:
- Starting dose: 12.5-25 mg daily
- Typical effective dose: 50-100 mg daily
- Maximum dose: 200-400 mg daily if necessary
- FDA-approved dosing for primary hyperaldosteronism: 100-400 mg daily 2, 3
b) Eplerenone (alternative if spironolactone not tolerated):
- Starting dose: 25 mg daily
- Less potent than spironolactone but fewer sexual side effects
- Requires twice-daily dosing 2
3. Special Cases
- Glucocorticoid-remediable aldosteronism: Low-dose dexamethasone 2
- Patients unsuitable for surgery: Long-term maintenance with spironolactone at lowest effective dose 3
Monitoring and Follow-up
Initial Monitoring
- Check serum potassium and renal function within 1-2 weeks of starting treatment
- Monitor for hyperkalemia, especially when combined with ACE inhibitors 2
Long-term Monitoring
- Potassium monitoring:
- 3 days after initiating therapy
- 1 week after initiating therapy
- Monthly for first 3 months
- Periodically thereafter 2
- Regular assessment of blood pressure control
- Watch for side effects:
- Gynecomastia and breast tenderness in men
- Menstrual irregularities in women
- Sexual dysfunction
- Hyperkalemia (especially with renal impairment) 2
Clinical Pearls and Pitfalls
Important Considerations
- Early diagnosis and treatment are critical to prevent vascular remodeling that may result in residual hypertension 2
- Bilateral adrenal hyperplasia accounts for ~60% of primary aldosteronism cases and requires lifelong medical therapy 2
- When using spironolactone, establish a consistent pattern regarding meals, as food increases bioavailability by approximately 95% 3
Medication Interactions
- Avoid concomitant use of potassium supplements, salt substitutes containing potassium, or potassium-sparing drugs
- Use caution when combining with ACE inhibitors, angiotensin II antagonists, or NSAIDs due to increased hyperkalemia risk 3
- Spironolactone reduces renal clearance of lithium, increasing risk of lithium toxicity 3
Treatment Outcomes
- Treating primary aldosteronism, either by mineralocorticoid receptor antagonists or unilateral adrenalectomy:
- Resolves hypokalemia
- Lowers blood pressure
- Reduces number of antihypertensive medications required
- Improves cardiac and kidney function 1
By following this structured approach to diagnosis and management, aldosterone dysregulation can be effectively treated, leading to improved blood pressure control and reduction in cardiovascular and renal complications.