What is the management approach for a patient with primary aldosteronism (elevated aldosterone) and low Adrenocorticotropic hormone (ACTH) levels?

Management of Elevated Aldosterone with Low ACTH

This clinical presentation suggests primary aldosteronism, and management depends critically on determining whether the disease is unilateral (surgical candidate) or bilateral (medical therapy), which requires confirmatory testing followed by adrenal vein sampling in most cases. 1

Understanding the Clinical Context

Low ACTH with elevated aldosterone indicates autonomous aldosterone production independent of the renin-angiotensin-aldosterone system, which is the hallmark of primary aldosteronism (Conn syndrome). 1 The low ACTH is expected because aldosterone excess causes volume expansion and hypertension, which suppresses the hypothalamic-pituitary-adrenal axis feedback. 1

Important caveat: Ensure the patient is not taking exogenous glucocorticoids (oral prednisolone, dexamethasone, or inhaled fluticasone), as these can suppress ACTH and confound interpretation. 1

Step 1: Confirm the Diagnosis

Before proceeding with subtype evaluation, you must confirm autonomous aldosterone secretion with one of the following tests: 2

• Intravenous saline suppression test: Infuse 2L normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms primary aldosteronism 2
• Oral sodium loading test: Measure 24-hour urine aldosterone while on high-sodium diet (>200 mEq/day for 3 days); elevated urinary aldosterone confirms the diagnosis 2
• Fludrocortisone suppression test: Alternative confirmatory option 2

Critical preparation requirements:

• Ensure potassium repletion (target 4.0-5.0 mEq/L) before testing, as hypokalemia suppresses aldosterone production and causes false-negatives 2
• Maintain unrestricted salt intake 2
• Withdraw mineralocorticoid receptor antagonists for at least 4 weeks before testing 2

Step 2: Determine Unilateral vs. Bilateral Disease

This distinction is mandatory because it determines whether the patient is a surgical candidate (unilateral disease) or requires lifelong medical therapy (bilateral disease). 1

Initial Imaging

• Obtain non-contrast CT scan of the adrenal glands 2

Adrenal Venous Sampling (AVS)

AVS is mandatory before offering adrenalectomy in most patients, as CT findings alone are insufficient—adenomas on imaging can represent hyperplasia, and false positives are common due to nodular hyperplasia. 2 Up to 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone. 2

Exception to AVS requirement: Patients <40 years old with a single unilateral adenoma on CT and normal contralateral adrenal can proceed directly to surgery, as bilateral hyperplasia is rare in this population. 2

Step 3: Treatment Based on Subtype

For Unilateral Disease (Aldosterone-Producing Adenoma or Unilateral Hyperplasia)

Laparoscopic unilateral adrenalectomy is the treatment of choice. 1, 2 This approach:

• Improves blood pressure in virtually 100% of patients 2
• Cures hypertension completely in approximately 50% of patients 2
• Normalizes hypokalemia 2
• Improves cardiac and kidney function parameters 2

Preoperative medical preparation: Administer spironolactone 100-400 mg daily to optimize blood pressure and potassium before surgery. 3

For Bilateral Disease (Idiopathic Adrenal Hyperplasia)

Medical therapy with mineralocorticoid receptor antagonists (MRAs) is the cornerstone of lifelong treatment. 1, 2

First-Line: Spironolactone

• Starting dose: 50-100 mg once daily 1
• Titration: Can increase up to 300-400 mg once daily if necessary 1
• FDA-approved dosing for primary hyperaldosteronism: 100-400 mg daily 3
• Monitoring: Watch for hyperkalemia, particularly in patients with renal impairment 2

Alternative: Eplerenone

• Less potent than spironolactone and requires twice-daily administration 1
• Advantage: Causes less gynaecomastia and erectile dysfunction in men 1

Emerging Agents

• Non-steroidal MRAs (finerenone, exarenone) and aldosterone synthase inhibitors (baxdrostat) are being tested for primary aldosteronism 1

Special Case: Familial Hyperaldosteronism Type 1 (Glucocorticoid-Remediable)

If family history suggests familial disease, genetic testing for germ-line mutations is necessary. 1 Familial hyperaldosteronism type 1 can be corrected with low-dose dexamethasone, which is free of glucocorticoid effects and safe during pregnancy. 1

Critical Follow-Up Considerations

Treatment Targets Beyond Blood Pressure

Goals should not be limited to normalizing blood pressure—prevention or correction of cardiovascular and renal complications is mandatory. 4 Primary aldosteronism confers excess cardiovascular and renal complications compared to essential hypertension, reflecting aldosterone's ability to cause tissue damage beyond hypertension itself. 4, 5

Post-Surgical Monitoring

Even after successful adrenalectomy, some patients have residual hypertension due to vascular remodeling from delayed diagnosis. 1 The rate of cure is higher when diagnosis is made early in the disease course. 1

Medical Therapy Monitoring

• Monitor serum potassium and renal function regularly, especially when initiating or titrating MRAs 2
• Ensure adequate blood pressure control and assess for medication side effects 1
• Consider that MRAs block toxic effects of aldosterone on nonepithelial tissues, providing cardiovascular protection beyond blood pressure reduction 6

Common Pitfalls to Avoid

• Do not rely on hypokalemia as a diagnostic criterion—it is absent in approximately 50% of primary aldosteronism cases 2
• Do not proceed to surgery based on CT findings alone without AVS (except in patients <40 years with clear unilateral adenoma) 2
• Do not forget to correct hypokalemia before confirmatory testing, as it suppresses aldosterone and causes false-negatives 2
• Do not overlook the need for specialized referral—patients with confirmed primary aldosteronism should be referred to a hypertension specialist or endocrinologist for subtype determination and treatment planning 1, 2