What are the signs and management of hyperaldosteronism?

Signs and Management of Hyperaldosteronism

Primary aldosteronism is characterized by hypertension, hypokalemia, suppressed plasma renin activity, and excessive aldosterone production, requiring targeted treatment with either mineralocorticoid receptor antagonists or adrenalectomy depending on whether the disease is bilateral or unilateral.

Clinical Signs and Symptoms

Common Presentations

• Hypertension: Often moderate to severe or resistant to standard treatment 1, 2
• Hypokalemia: Resulting in:
  • Muscle weakness
  • Muscle cramping
  • Fatigue
  • Headaches
  • Intermittent paralysis in severe cases 2
• Metabolic alkalosis: Due to increased sodium retention and potassium excretion 1

Physical Examination Findings

• Elevated blood pressure (may be resistant to multiple medications)
• Normal physical examination in many cases
• Absence of edema (unlike other causes of secondary hypertension)
• No specific physical stigmata (unlike Cushing syndrome)

Laboratory Abnormalities

• Low serum potassium (though 30-50% of patients may be normokalemic)
• Elevated plasma aldosterone level
• Suppressed plasma renin activity
• Elevated aldosterone-to-renin ratio (ARR) ≥20-30 2

Diagnostic Approach

Screening

1. Who to screen:

   • Patients with resistant hypertension
   • Hypertension with spontaneous or diuretic-induced hypokalemia
   • Hypertension with adrenal incidentaloma
   • Early-onset hypertension or family history of early-onset hypertension
   • Severe hypertension (>180/110 mmHg) 1, 2

2. Initial screening test:

   • Morning aldosterone-to-renin ratio (ARR) with patient seated for 5-15 minutes before collection 2
   • ARR ≥20 ng/dL per ng/mL/hr with plasma aldosterone ≥10 ng/dL is considered positive 2

3. Important considerations for testing:

   • Ensure patient is potassium-replete
   • Consider medication effects on ARR (see below)
   • Consider menstrual cycle timing in females 2

Medications Affecting ARR Testing 1

• False positives: Beta-blockers, NSAIDs, alpha-2 agonists, steroids
• False negatives: ACE inhibitors, ARBs, diuretics, calcium channel blockers

Confirmatory Testing

After positive screening, one of the following is recommended 2:

• Intravenous saline suppression test
• Oral salt-loading test with 24-hour urine aldosterone measurement
• Fludrocortisone suppression test

Subtype Determination

1. Imaging:

   • Non-contrast CT scan of adrenal glands (or MRI if CT contraindicated) 2

2. Adrenal vein sampling (AVS):

   • Gold standard for distinguishing unilateral from bilateral disease
   • Recommended prior to adrenalectomy, particularly in:
     • Patients >40 years old
     • Normal-appearing adrenal glands on imaging
     • Discordance between biochemical and imaging results 2

Management

For Unilateral Disease (Aldosterone-producing adenoma)

• Laparoscopic adrenalectomy is the treatment of choice 1, 2
• Outcomes:
  • Improves blood pressure in nearly 100% of patients
  • Complete cure of hypertension in ~50% of patients
  • Normalizes potassium levels 2

For Bilateral Disease (Idiopathic hyperaldosteronism)

• Medical therapy with mineralocorticoid receptor antagonists:

  1. Spironolactone (first-line) 3, 4:

     • Initial dose: 12.5-25 mg daily 4
     • Titrate up to 100 mg daily as needed 4
     • Monitor for side effects: gynecomastia, erectile dysfunction, menstrual irregularities

  2. Eplerenone (alternative):

     • 50-100 mg daily 4
     • Fewer anti-androgenic side effects but less potent and more expensive

Dosing for Primary Hyperaldosteronism 3

• For medical management: 100-400 mg daily of spironolactone
• For preoperative preparation: 100-400 mg daily of spironolactone

Additional Treatment Considerations

• Potassium supplementation: May be needed initially until medical therapy takes effect
• Additional antihypertensives: May be required if blood pressure control is inadequate
  • Calcium channel blockers are often effective 4
  • Potassium-sparing diuretics (amiloride, triamterene) can be added 4

Monitoring

• Regular monitoring of:
  • Blood pressure
  • Serum potassium levels
  • Renal function
  • Signs of cardiovascular damage 2
• For patients on mineralocorticoid receptor antagonists:
  • Monitor for hyperkalemia, especially at initiation and with dose increases
  • Particularly important in patients with reduced renal function 2

Prognosis

With appropriate treatment, primary hyperaldosteronism has excellent outcomes 2:

• Reduction in blood pressure
• Normalization of potassium levels
• Reversal of left ventricular hypertrophy
• Reduction in cardiovascular and renal complications

Common Pitfalls

1. Underdiagnosis: Primary aldosteronism is significantly underdiagnosed, with screening rates as low as 2-4% even in high-risk groups 2
2. Medication interference: Many antihypertensive medications can affect the ARR, leading to false results 1
3. Relying solely on imaging: CT/MRI findings alone are insufficient to determine unilateral vs. bilateral disease in many cases, making AVS crucial 2
4. Inadequate potassium replacement: Ensuring potassium repletion before testing is essential for accurate results 2