How to manage worsening hypertension in a patient with elevated aldosterone and normal renal doppler?

Management of Worsening Hypertension with Elevated Aldosterone

This patient requires further evaluation for primary aldosteronism with 24-hour urinary aldosterone after oral salt loading, followed by initiation of spironolactone 25-50 mg daily as the most effective treatment for resistant hypertension with aldosterone excess. 1, 2

Immediate Diagnostic Priority: Confirm Primary Aldosteronism

Your patient's aldosterone-to-renin ratio (ARR) of 2.8 is not elevated enough to diagnose primary aldosteronism by traditional screening criteria, but this does not exclude the diagnosis. 1

• The ARR has poor sensitivity and negative predictive value, particularly when renin is suppressed, which appears to be the case here with renin at 10.3. 1
• Recent evidence demonstrates that up to 22% of patients with hypertension have primary aldosteronism despite a negative ARR screening test. 1
• Proceed directly to 24-hour urinary aldosterone excretion after oral salt loading (using >12 µg/24h as the diagnostic threshold), as this is more sensitive than ARR alone in detecting aldosterone excess states. 1

Critical pitfall to avoid: Do not rely solely on the ARR to exclude primary aldosteronism in patients with worsening or resistant hypertension. 1

Pharmacological Management Strategy

First-Line Addition: Mineralocorticoid Receptor Antagonist

Add spironolactone 25 mg once daily immediately, even before confirmatory testing is complete, given the worsening hypertension. 1, 3, 2

• Spironolactone is the most effective agent for resistant hypertension and works regardless of whether formal primary aldosteronism is confirmed. 2
• The PATHWAY-2 trial demonstrated superior efficacy of spironolactone over other agents in resistant hypertension, supporting the concept of a spectrum of aldosterone excess. 1
• Titrate to 50 mg daily after 4 weeks if blood pressure remains uncontrolled and potassium remains ≤5.0 mEq/L. 3
• Monitor serum potassium and creatinine at 1 week, 4 weeks, then every 3 months. 1, 3

Alternative if Spironolactone Not Tolerated

If the patient develops gynecomastia or other antiandrogenic side effects (occurs in up to 10% of men), switch to eplerenone 50-100 mg daily, which has greater selectivity for the mineralocorticoid receptor. 4

Blood Pressure Target

Target blood pressure <130/80 mmHg for this 36-year-old patient with resistant hypertension. 1

• In younger patients with isolated hypertension, lifetime cardiovascular risk is substantially elevated, warranting aggressive blood pressure control. 1
• The 2024 ESC guidelines recommend systolic blood pressure of 120-129 mmHg if tolerated in most adults receiving treatment. 1

Additional Antihypertensive Therapy if Needed

If blood pressure remains uncontrolled on spironolactone:

• Add a long-acting dihydropyridine calcium channel blocker (amlodipine 5-10 mg daily) as the next step. 1
• Consider chlorthalidone 12.5-25 mg daily instead of hydrochlorothiazide, as it is more potent and longer-acting for resistant hypertension. 2
• Ensure the patient is on maximum tolerated doses of ACE inhibitor or ARB as foundational therapy. 1

Do not combine ACE inhibitors with ARBs, as this increases adverse effects without additional benefit. 1

Lifestyle Modifications

Sodium restriction to <2 grams per day is essential, as aldosterone excess causes sodium retention and volume expansion. 1

• Reinforce dietary sodium restriction aggressively, as this enhances the effectiveness of mineralocorticoid receptor antagonists. 1
• Weight loss if overweight/obese, as visceral adipocytes may contribute to aldosterone excess. 2
• Regular aerobic exercise 150 minutes per week. 1

Monitoring for Hyperkalemia

Check serum potassium within 1 week of starting spironolactone, then at 4 weeks, then every 3 months. 3

• If potassium rises to 5.5-5.9 mEq/L: reduce spironolactone to 25 mg every other day. 3
• If potassium ≥6.0 mEq/L: discontinue spironolactone and reassess. 3
• Avoid potassium supplements and potassium-enriched salt substitutes while on spironolactone. 1

When to Refer for Adrenal Imaging

If 24-hour urinary aldosterone is >12 µg/24h after salt loading, proceed with adrenal CT scan to differentiate unilateral aldosterone-producing adenoma from bilateral adrenal hyperplasia. 1

• Unilateral disease (adenoma) may be curable with adrenalectomy in a young patient. 1
• Bilateral disease (idiopathic hyperaldosteronism) requires lifelong medical management with spironolactone. 1, 5
• Consider referral to a hypertension specialist for adrenal vein sampling if imaging shows unilateral abnormality and surgical cure is being considered. 1