What is the management and treatment approach for a patient diagnosed with hyperaldosteronism?

Management and Treatment of Hyperaldosteronism

Immediate First Step: Determine Primary vs Secondary Hyperaldosteronism

The critical first decision is distinguishing primary from secondary hyperaldosteronism, as this fundamentally determines treatment strategy—primary hyperaldosteronism requires either surgery or lifelong mineralocorticoid receptor antagonist therapy, while secondary hyperaldosteronism requires treating the underlying condition. 1, 2

• Measure plasma aldosterone concentration and plasma renin activity simultaneously 1, 2
• In primary hyperaldosteronism: aldosterone is elevated AND renin is suppressed (aldosterone/renin ratio ≥20-30) 3
• In secondary hyperaldosteronism: BOTH aldosterone AND renin are elevated 1, 2
• Ensure potassium repletion before testing, as hypokalemia suppresses aldosterone production and causes false-negative results 3

Management of Primary Hyperaldosteronism

Step 1: Confirm the Diagnosis

After positive screening (ARR ≥20-30 with aldosterone ≥10-15 ng/dL), confirmatory testing is mandatory 3:

• Intravenous saline suppression test: Infuse 2L normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms autonomous secretion 3
• Oral sodium loading test: Measure 24-hour urine aldosterone after 3 days of high salt intake 3, 2
• Testing must be performed with unrestricted salt intake and normal serum potassium 3
• Critical caveat: Mineralocorticoid receptor antagonists (spironolactone, eplerenone) must be withdrawn at least 4 weeks before any confirmatory testing 3

Step 2: Determine Unilateral vs Bilateral Disease

This distinction is absolutely mandatory because it determines whether the patient is a surgical candidate (unilateral) or requires lifelong medical therapy (bilateral). 3, 2

• Obtain non-contrast CT scan of adrenal glands as initial imaging 3
• Adrenal venous sampling (AVS) is the gold standard and mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease 3, 2
• Exception: AVS may be omitted in patients <40 years with imaging showing a single affected gland, as bilateral hyperplasia is rare in this population 3
• Never proceed to surgery based on CT findings alone—up to 25% of patients would undergo unnecessary adrenalectomy without AVS 3

Step 3: Treatment Based on Subtype

For Unilateral Disease (Aldosterone-Producing Adenoma):

Laparoscopic unilateral adrenalectomy is the definitive treatment of choice and should be offered to all surgical candidates. 3, 2, 4

• Surgery improves blood pressure in virtually 100% of patients 3, 2
• Complete cure of hypertension occurs in approximately 50% of cases 3, 2
• Adrenalectomy normalizes hypokalemia, reduces antihypertensive medication requirements, and improves cardiac and kidney function 3
• Early diagnosis and treatment are crucial—delayed diagnosis leads to irreversible vascular remodeling causing persistent hypertension even after successful surgery 3, 2

For Bilateral Disease (Bilateral Adrenal Hyperplasia) or Non-Surgical Candidates:

Spironolactone is the first-line medical treatment and cornerstone of lifelong therapy. 3, 2, 4, 5

Specific dosing algorithm:

1. Start spironolactone 25-50 mg once daily (FDA-approved starting dose for primary hyperaldosteronism is 100 mg daily, but clinical practice often begins lower to minimize side effects) 3, 2, 4, 5
2. Titrate gradually: Increase to 100 mg/day after 2-4 weeks if blood pressure remains uncontrolled 2, 5
3. Maximum dose: 200-400 mg/day for primary hyperaldosteronism 2, 4, 5
4. Monitor closely: Check serum potassium and creatinine within 1 week of initiation and with each dose adjustment 3, 2

Alternative agent:

• Eplerenone can be used as an alternative in patients who cannot tolerate spironolactone side effects (particularly gynecomastia, breast tenderness, decreased libido, erectile dysfunction) 3, 1, 2
• Eplerenone is less potent than spironolactone and requires twice-daily dosing at 50-100 mg/day 3, 5

Additional therapy if needed:

• Add potassium-sparing diuretics (amiloride or triamterene) if blood pressure not controlled on maximum spironolactone 5
• Add calcium channel blockers as third-line agents 5

Critical Monitoring Parameters

Monitor the following at each visit and with dose adjustments: 2

• Serum potassium (risk of hyperkalemia, especially in patients with renal impairment, diabetes, or concurrent ACE inhibitor/ARB use) 3, 2
• Serum creatinine (may increase with spironolactone, particularly in patients with pre-existing kidney damage from severe hypertension) 2, 6
• Blood pressure and fluid status 1, 2
• Potassium supplementation may be necessary if hypokalemia persists despite treatment 1, 2

Special Consideration: Patients with Renal Impairment

In patients with severe hypertension and secondary kidney damage, spironolactone may cause marked increases in serum creatinine and hyperkalemia due to decreased filtered sodium load. 6

• Start with lower doses (25 mg every other day) in patients with eGFR 30-50 mL/min/1.73 m² 4
• Monitor potassium and creatinine even more closely 6
• Despite these risks, early specific treatment is still indicated as even patients with advanced hypertension benefit from targeted therapy 6

Management of Secondary Hyperaldosteronism

Treat the underlying condition causing elevated renin and aldosterone (heart failure, cirrhosis, nephrotic syndrome, renal artery stenosis). 1, 2

• Address fluid and sodium depletion to correct the hyperaldosteronism 7
• Mineralocorticoid receptor antagonists may be used symptomatically but do not address the root cause 1
• Monitor electrolytes and renal function closely 1

Common Pitfalls to Avoid

• Never rely on presence or absence of hypokalemia alone—it is absent in approximately 50% of primary aldosteronism cases 3
• Never proceed to adrenalectomy based on CT findings alone without adrenal venous sampling (except in patients <40 years with unilateral adenoma) 3
• Never perform confirmatory testing while patient is taking spironolactone or eplerenone—requires 4-week washout 3
• Never test patients who are hypokalemic—correct potassium first as hypokalemia suppresses aldosterone production 3
• Do not delay diagnosis—early treatment prevents irreversible cardiovascular and renal complications that carry 3.7-fold increased heart failure risk, 4.2-fold increased stroke risk, and 12.1-fold increased atrial fibrillation risk compared to essential hypertension 3