How does hyperaldosteronism affect potassium levels?

Hyperaldosteronism Causes Hypokalemia

Hyperaldosteronism causes hypokalemia by increasing renal potassium excretion through aldosterone's action on the distal renal tubules. This occurs through aldosterone's competitive binding to mineralocorticoid receptors in the kidney, which promotes sodium retention and potassium excretion 1, 2.

Mechanism of Action

Aldosterone acts primarily through the following mechanisms:

• Distal tubular effect: Aldosterone binds to mineralocorticoid receptors in the distal convoluted renal tubule, causing increased sodium reabsorption and potassium excretion 2
• Ion exchange: Promotes sodium-potassium exchange in the distal tubule, where sodium is retained and potassium is excreted 2
• Increased potassium secretion: Enhances the activity of the sodium-potassium ATPase pump, leading to increased urinary potassium loss 1

Clinical Manifestations

In primary aldosteronism:

• Hypokalemia is a classic finding, with serum potassium typically <3.5 mEq/L 1
• Hypertension is nearly universal and often resistant to conventional therapy 1
• Metabolic alkalosis frequently accompanies hypokalemia 3
• Suppressed plasma renin activity is characteristic 1

Diagnosis and Evaluation

The diagnosis of hyperaldosteronism should be considered in patients with:

• Hypertension with spontaneous or diuretic-induced hypokalemia 1
• Resistant hypertension (requiring ≥3 medications) 1
• Severe hypertension (>180/110 mmHg) 1
• Early-onset hypertension or family history of early-onset hypertension 1

The recommended diagnostic approach includes:

1. Initial screening: Plasma aldosterone-to-renin ratio (ARR) with a sensitivity >90% when properly performed 1
2. Positive screening: ARR ≥20 ng/dL per ng/mL/hr with plasma aldosterone ≥10 ng/dL 1
3. Confirmatory testing: Intravenous saline suppression test, oral salt-loading test, or fludrocortisone suppression test 1

Management of Hyperaldosteronism and Hypokalemia

Treatment depends on whether the disease is unilateral or bilateral:

• Unilateral disease: Laparoscopic adrenalectomy is the treatment of choice, improving blood pressure in virtually 100% of patients and curing hypertension in ~50% 1

• Bilateral disease or non-surgical candidates: Medical therapy with mineralocorticoid receptor antagonists:

  • Spironolactone: Initial dose 12.5-25 mg daily, titrating up to 100 mg daily as needed 1, 4
  • Eplerenone: Alternative with fewer anti-androgenic side effects 4, 5

Monitoring and Precautions

When using mineralocorticoid receptor antagonists:

• Potassium monitoring: Check potassium levels within 3 days and again at 1 week after initiation, then monthly for 3 months and every 3 months thereafter 4
• Potassium supplementation: Generally discontinued after starting aldosterone antagonists 4
• Medication interactions: Avoid NSAIDs, COX-2 inhibitors, ACE inhibitors, ARBs, and potassium supplements which can increase hyperkalemia risk 4, 2
• Discontinuation criteria: Consider stopping or reducing dose if potassium exceeds 5.5 mEq/L or renal function worsens 4

Special Considerations

• Patients should be counseled to avoid high potassium-containing foods 4
• Aldosterone antagonists should be temporarily stopped during episodes of diarrhea or when loop diuretic therapy is interrupted 4
• Acute potassium chloride supplementation in patients with primary aldosteronism can suppress sodium-chloride cotransporter activity despite rising aldosterone levels 6
• The routine triple combination of ACEIs, ARBs, and aldosterone antagonists should be avoided due to hyperkalemia risk 4

Proper management of hyperaldosteronism not only corrects hypokalemia but also reduces cardiovascular and renal complications associated with this condition 1.