What is primary hyperaldosteronism?

Primary Hyperaldosteronism

Primary hyperaldosteronism is characterized by autonomous aldosterone production from the adrenal glands, representing the most common endocrine cause of hypertension with a prevalence of up to 12% in patients with severe hypertension. 1 This condition is significantly underdiagnosed, with screening rates as low as 2-4% even in high-risk groups.

Clinical Presentation and Screening

Who Should Be Screened

Screening for primary aldosteronism is recommended in 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
• Symptoms such as muscle cramping, weakness, headaches, or intermittent paralysis 1

Screening Process

• Morning collection (preferably between 8-10 AM)
• Patient seated for 5-15 minutes before collection
• Ensure patient is potassium-replete
• Consider menstrual cycle timing in females when interpreting results 1

Diagnostic Approach

Initial Testing

• Aldosterone-to-renin ratio (ARR) is the preferred initial test
• ARR ≥20 ng/dL per ng/mL/hr with plasma aldosterone ≥10 ng/dL is considered positive
• This has excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism 1

Confirmatory Testing

If ARR is positive, one of the following confirmatory tests should be performed:

• Intravenous saline suppression test
• Oral salt-loading test with 24-hour urine aldosterone measurement
• Fludrocortisone suppression test 1

Imaging and Subtype Differentiation

• Non-contrast CT scan of adrenal glands (or MRI if CT is contraindicated) after biochemical confirmation
• Adrenal vein sampling (AVS) is the gold standard for distinguishing between unilateral and bilateral aldosterone production
• AVS is particularly important in patients >40 years, those with normal-appearing adrenal glands on imaging, or when there's discordance between biochemical and imaging results 1

Treatment Options

For Unilateral Disease

• Laparoscopic adrenalectomy is the treatment of choice for unilateral disease, improving blood pressure in virtually 100% of patients and achieving complete cure of hypertension in approximately 50% of cases. 1
• Preoperative treatment with spironolactone at doses of 100-400 mg daily is recommended 2

For Bilateral Disease or Non-Surgical Candidates

• Medical therapy with mineralocorticoid receptor antagonists (MRAs)
• Spironolactone is the preferred initial agent due to lower cost and greater availability 3
• Dosing:
  • Initial dose: 25-100 mg daily (administered in single or divided doses)
  • Can be titrated at two-week intervals
  • For long-term maintenance, use the lowest effective dosage 2
• Monitor for hyperkalemia, especially in patients with reduced renal function 1
• Titrate MRA to increase renin in patients whose hypertension remains uncontrolled and renin is suppressed 3

Monitoring and Follow-up

Regular monitoring should include:

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

Outcomes and Prognosis

With appropriate treatment, primary hyperaldosteronism has excellent outcomes, including:

• Reduction in blood pressure
• Normalization of potassium levels
• Reversal of left ventricular hypertrophy
• Reduction in cardiovascular and renal complications 1

Common Pitfalls to Avoid

1. Underdiagnosis: Despite being common, primary aldosteronism is significantly underdiagnosed, with screening rates as low as 2-4% even in high-risk groups 1

2. Medication interference: Several medications can interfere with ARR testing. When possible, medications that affect the renin-angiotensin-aldosterone system should be discontinued before testing.

3. Inadequate subtype differentiation: Failure to properly differentiate between unilateral and bilateral disease can lead to inappropriate treatment selection.

4. Overlooking dexamethasone suppression testing: In patients with PA and adrenal adenoma, a 1-mg overnight dexamethasone suppression test should be performed to rule out subclinical Cushing's syndrome 3

5. Insufficient monitoring: Patients on MRAs require regular monitoring for hyperkalemia, especially at initiation of therapy and with dose increases 1