What is the appropriate management for an adult patient with a history of hypertension, presenting with hyperaldosteronism and hyporeninemia?

Management of Hyperaldosteronism with Hyporeninemia

This patient has confirmed primary aldosteronism based on an aldosterone/renin ratio >100 (10.2 ng/dL divided by <0.1 ng/mL/h) with aldosterone ≥10 ng/dL, and requires immediate confirmatory testing followed by subtype determination with adrenal venous sampling to determine if surgical cure via unilateral adrenalectomy is possible. 1, 2

Immediate Next Steps

Confirmatory Testing Required

• Proceed directly to confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed with sodium loading, as screening tests alone are insufficient for definitive diagnosis 1, 3
• Perform either an intravenous saline suppression test (2L normal saline over 4 hours, with failure to suppress plasma aldosterone below 5 ng/dL confirming diagnosis) or an oral sodium loading test (24-hour urine aldosterone measurement after 3 days of high sodium intake) 1, 2
• Ensure the patient has unrestricted salt intake and normal serum potassium before confirmatory testing, as hypokalemia suppresses aldosterone production and causes false-negative results 1, 2

Critical Subtype Determination

• Order non-contrast CT scan of the adrenal glands immediately as initial imaging to identify unilateral adenoma versus bilateral hyperplasia 1, 3
• Adrenal venous sampling (AVS) is mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease, as CT findings alone are insufficient—up to 25% of patients would undergo unnecessary surgery based on imaging alone 2, 4
• The only exception to AVS requirement is patients <40 years old with imaging showing a single affected gland, as bilateral hyperplasia is rare in this population 2

Treatment Algorithm Based on Subtype

For Unilateral Disease (Aldosterone-Producing Adenoma)

• Laparoscopic unilateral adrenalectomy is the definitive treatment of choice, improving blood pressure in virtually 100% of patients and achieving complete cure of hypertension in approximately 50% 1, 5
• Surgery also normalizes hypokalemia, reduces antihypertensive medication requirements, and reverses target organ damage including left ventricular hypertrophy and renal dysfunction 1, 6
• Refer to an experienced endocrine surgeon for laparoscopic approach 3

For Bilateral Disease (Idiopathic Hyperaldosteronism)

• Initiate spironolactone 100-400 mg daily as first-line medical therapy for long-term management 7, 8
• Start at 100 mg daily and titrate based on blood pressure response and potassium levels 8
• Eplerenone 50-100 mg daily is an alternative for patients who develop gynecomastia, breast tenderness, or sexual dysfunction on spironolactone, though it is less potent and requires twice-daily dosing 5

Critical Safety Monitoring

Before Initiating Mineralocorticoid Receptor Antagonists

• Verify serum potassium ≤5.0 mEq/L and confirm serum creatinine <2.0-2.5 mg/dL or eGFR >30 mL/min 5
• Discontinue all potassium supplements and avoid combining with potassium-sparing diuretics 5, 8
• Exercise extreme caution when combining with ACE inhibitors, ARBs, or NSAIDs due to dramatically increased hyperkalemia risk 5

Monitoring Schedule

• Check potassium and creatinine at 3 days, 1 week, then monthly for the first 3 months, and subsequently every 3 months if stable 5
• Patients with renal impairment (eGFR <45 mL/min) or those taking ACE inhibitors/ARBs have significantly increased risk of life-threatening hyperkalemia 5, 9

Common Pitfalls to Avoid

Diagnostic Errors

• Do not rely on presence or absence of hypokalemia—it is absent in approximately 50% of confirmed primary aldosteronism cases 1, 2
• Never proceed to surgery based on CT findings alone without adrenal venous sampling, as imaging has poor specificity for lateralization 2, 4
• Do not dismiss the diagnosis if renin is not completely suppressed—patients with severe hypertensive kidney damage can have "escape" of renin from suppression while still having primary aldosteronism 9

Treatment Considerations

• Early diagnosis and treatment are critical—delayed treatment leads to irreversible vascular remodeling, resulting in persistent hypertension even after successful adrenalectomy 2, 5
• Patients with this condition have 3.7-fold increased heart failure, 4.2-fold increased stroke, 6.5-fold increased MI, and 12.1-fold increased atrial fibrillation compared to essential hypertension at equivalent blood pressure levels 1

Referral Recommendations

• Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination and treatment planning 2, 3
• Adrenal venous sampling should be performed at specialized centers with experienced interventional radiologists to ensure accurate lateralization 2, 3