What is the best management approach for Conn's syndrome (primary aldosteronism)?

Management of Conn's Syndrome (Primary Aldosteronism)

Laparoscopic unilateral adrenalectomy is the definitive treatment for unilateral disease (aldosterone-producing adenoma or unilateral hyperplasia), while mineralocorticoid receptor antagonists—specifically spironolactone as first-line—are the cornerstone of therapy for bilateral adrenal hyperplasia. 1, 2

Diagnostic Workup and Subtype Classification

Before initiating treatment, you must determine whether the disease is unilateral or bilateral, as this fundamentally dictates management 1, 2:

• Screen with plasma aldosterone-to-renin ratio (cutoff >30 when aldosterone is in ng/dL and renin activity in ng/mL/h, with aldosterone ≥10 ng/dL) 1
• Confirm diagnosis with saline suppression test or oral salt-loading test 1
• Perform adrenal vein sampling to distinguish unilateral from bilateral disease—this is the gold standard and should be done in specialized centers before surgery 1, 2
• Approximately 50% of cases are unilateral (usually adenoma) and 50% are bilateral (idiopathic hyperaldosteronism) 1, 2

Critical caveat: Hypokalemia is absent in the majority of primary aldosteronism cases and has low negative predictive value for diagnosis 1, 2. Do not exclude the diagnosis based on normal potassium levels.

Treatment Algorithm Based on Disease Subtype

For Unilateral Disease (Adenoma or Unilateral Hyperplasia)

Laparoscopic unilateral adrenalectomy is the treatment of choice 1, 2, 3:

• Improves blood pressure in virtually 100% of patients 2, 3
• Achieves complete cure of hypertension in approximately 50% of cases 2, 3
• Normalizes hypokalemia in all patients 4
• Reverses aldosterone-specific target organ damage including left ventricular hypertrophy and albuminuria 5

For patients who are not surgical candidates or decline surgery, proceed to medical therapy with mineralocorticoid receptor antagonists 2, 5

For Bilateral Disease (Idiopathic Hyperaldosteronism)

Medical therapy with mineralocorticoid receptor antagonists is the definitive treatment 1, 2, 3:

First-line: Spironolactone 2, 5, 6:

• Start at 50-100 mg daily (FDA-approved dosing for primary hyperaldosteronism: 100-400 mg daily) 6
• Titrate up to 300-400 mg daily if necessary for blood pressure control 5, 3
• Can be given as single or divided doses 6

Alternative: Eplerenone 2:

• Use 50-100 mg daily in 1-2 doses 2
• Fewer sexual side effects compared to spironolactone (gynecomastia, menstrual irregularities) 2

If blood pressure remains uncontrolled on adequate MRA dosing, add potassium-sparing diuretics (amiloride or triamterene) or calcium channel antagonists 7

Special Subtype: Familial Hyperaldosteronism Type 1

Low-dose dexamethasone is the treatment for glucocorticoid-remediable aldosteronism 2, 3

Monitoring and Safety Considerations

Critical monitoring requirements when initiating MRA therapy 7:

• Check serum potassium and creatinine closely at treatment initiation and during dose titration 7
• Avoid combining MRAs with other potassium-sparing medications or potassium supplements due to severe hyperkalemia risk 2
• Use MRAs with extreme caution if eGFR <45 mL/min 2
• Do not combine MRAs with ACE inhibitors or ARBs without careful monitoring due to additive hyperkalemia risk 2

Timing and Prognostic Considerations

Early diagnosis and treatment are critical 2, 5:

• Delayed diagnosis leads to irreversible vascular remodeling that causes residual hypertension even after appropriate treatment 2, 5
• Aldosterone excess causes aldosterone-specific cardiovascular and renal damage beyond simple blood pressure effects 1, 5
• Target organ damage (left ventricular hypertrophy, albuminuria, carotid intima-media thickness) can be reversed with appropriate MRA therapy 5

Referral Indications

Refer to hypertension specialist or endocrinologist 1:

• All patients with positive screening test for primary aldosteronism 1
• Complex cases or rare forms of primary aldosteronism 5
• For adrenal vein sampling, which should be performed in specialized centers 2

Common Pitfalls to Avoid

• Do not rely on hypokalemia for diagnosis—most patients are normokalemic 1, 2
• Do not use CT imaging alone to determine laterality—adrenal vein sampling is required for accurate subtype determination 1, 2
• In patients <40 years with unilateral adenoma on imaging, adrenal vein sampling may be reasonably excluded as bilateral hyperplasia is rare in this population 1
• Suspect malignancy if the tumor is >3 cm, has irregular morphology, is lipid-poor, does not wash out on contrast CT, or secretes multiple hormones—these require open adrenalectomy 1
• Withdraw spironolactone/eplerenone for at least 4 weeks before screening tests to avoid false results 1