What are the steps to diagnose and manage hyperaldosteronism?

Diagnosing and Managing Hyperaldosteronism

The diagnosis of hyperaldosteronism requires a systematic approach beginning with screening using the aldosterone-to-renin ratio (ARR), followed by confirmatory testing, subtype differentiation, and targeted treatment based on whether the condition is unilateral or bilateral. 1

Screening Process

Who to Screen

• Patients with:
  • Resistant hypertension
  • Hypertension with spontaneous or diuretic-induced hypokalemia
  • Adrenal incidentaloma
  • Early-onset hypertension
  • Family history of early-onset hypertension or stroke at young age (<40 years)
  • Unilateral adrenal masses 1

Initial Screening Test

• Aldosterone-to-renin ratio (ARR) is the most reliable first-line screening test
  • Cutoff value ≥30 when plasma aldosterone is reported in ng/dL and plasma renin activity in ng/mL/h
  • Plasma aldosterone should be at least 10 ng/dL for a positive test 1, 2

Testing Conditions for ARR

• Morning measurement with patient seated for 5-15 minutes
• Unrestricted salt intake
• Normal serum potassium levels
• Withdrawal of interfering medications when possible:
  • Mineralocorticoid receptor antagonists (withdraw for at least 4 weeks)
  • Direct renin inhibitors
  • β-blockers 1, 2

Important caveat: Normal potassium levels do not exclude hyperaldosteronism. Up to 20% of patients with primary aldosteronism have normal serum potassium levels 3, 4.

Confirmatory Testing

After a positive ARR screening, confirmatory testing is required:

• Intravenous saline suppression test
• Oral salt loading test
• Fludrocortisone suppression test 1, 2

These tests confirm autonomous aldosterone production that fails to suppress with volume expansion.

Subtype Differentiation

Imaging

• Non-contrast CT scan of adrenal glands as first-line imaging
• MRI as alternative if CT is contraindicated 1

Adrenal Venous Sampling (AVS)

• Gold standard for distinguishing between unilateral and bilateral aldosterone production
• Recommended prior to adrenalectomy, particularly in:
  • Patients >40 years
  • Normal-appearing adrenal glands on imaging
  • Discordance between biochemical and imaging results 1

Treatment Based on Subtype

Unilateral Disease (Aldosterone-Producing Adenoma)

• Laparoscopic adrenalectomy is the treatment of choice
  • Improves blood pressure in virtually 100% of patients
  • Achieves complete cure of hypertension in approximately 50% 1, 2

Bilateral Disease (Idiopathic Hyperaldosteronism) or Non-Surgical Candidates

• Medical therapy with mineralocorticoid receptor antagonists:

  • Spironolactone: Starting at 25-100 mg daily, titrating up to 400 mg daily as needed 1, 5
  • For primary hyperaldosteronism: 100-400 mg daily 5
  • Monitor for hyperkalemia, especially in patients with reduced renal function 1
  • Eplerenone is an alternative with fewer side effects 2

• If blood pressure is not normalized, additional treatment options include:

  • Potassium-sparing diuretics (amiloride or triamterene)
  • Calcium channel antagonists 6

Monitoring and Follow-up

• Regular monitoring of:

  • Blood pressure
  • Serum potassium levels
  • Renal function
  • Signs of cardiovascular damage 1

• After adrenalectomy:

  • Monitor for resolution of hypertension and normalization of potassium levels
  • Some patients may still require antihypertensive medication 1

• For medical therapy:

  • Titrate medication to achieve target blood pressure
  • Monitor for hyperkalemia, especially at initiation of therapy and with dose increases 1, 5

With appropriate treatment, primary hyperaldosteronism has excellent outcomes, including reduction in blood pressure, normalization of potassium levels, reversal of left ventricular hypertrophy, and reduction in cardiovascular and renal complications 1.