What is the management and diagnosis of primary hypoaldosteronism?

Primary Hypoaldosteronism: Diagnosis and Management

Diagnosis

The diagnosis of primary hypoaldosteronism requires demonstrating low aldosterone levels in the context of hyperkalemia and/or hyponatremia, with elevated plasma renin activity (PRA) distinguishing it from secondary causes. 1

Clinical Presentation

The key clinical features to identify include:

• Hyperkalemia (present in 94.6% of cases) is the hallmark finding 2
• Hypovolemic hyponatremia occurs in approximately 54.5% of cases due to renal salt wasting 2
• Metabolic acidosis (type 4 renal tubular acidosis) develops in 60.3% of patients due to impaired ammonia production from hyperkalemia 3, 2
• Hypotension or postural hypotension reflects insufficient mineralocorticoid activity and volume depletion 4, 3
• Salt craving and symptoms of volume depletion 1

Diagnostic Testing

Measure paired plasma aldosterone concentration (PAC) and plasma renin activity (PRA) simultaneously - this is the cornerstone of diagnosis 4:

• Low aldosterone levels with elevated PRA confirms primary hypoaldosteronism (distinguishing it from secondary hypoaldosteronism where both are low) 3
• The stimulated PAC/serum potassium ratio below 3 is highly specific for hypoaldosteronism 5
• Check serum electrolytes: sodium, potassium, bicarbonate, and creatinine 4

Important diagnostic pitfall: Normal potassium levels do not exclude hypoaldosteronism - approximately 50% of patients may be normokalemic 2. Additionally, hyponatremia with urinary sodium wasting should prompt consideration of hypoaldosteronism in the differential diagnosis 2.

Distinguishing Primary from Pseudohypoaldosteronism

• Type I pseudohypoaldosteronism shows normal or elevated aldosterone levels with elevated PRA, indicating aldosterone resistance at the renal tubule 3, 5
• Type II pseudohypoaldosteronism presents with hypertension (unlike primary hypoaldosteronism which causes hypotension) due to chloride hyperabsorption 3

Management

Fludrocortisone 50-200 μg once daily in the morning, combined with liberal salt intake, is the definitive treatment for primary hypoaldosteronism. 1

Mineralocorticoid Replacement

• Start fludrocortisone at 50-200 μg once daily, taken in the morning 1
• Higher doses (up to 200 μg) may be required in children and younger adults 1
• Encourage unrestricted salt and salty food consumption to maintain adequate sodium balance 1
• Avoid potassium-containing salt substitutes 1

Monitoring Treatment Efficacy

Clinical parameters to assess regularly 1:

• Blood pressure (should normalize; postural hypotension indicates under-replacement) 4
• Weight stability 4
• Absence of peripheral edema (suggests over-replacement)
• Resolution of salt cravings and lightheadedness 1

Laboratory monitoring 4, 1:

• Serum sodium and potassium levels
• Assessment of PRA can help guide dosing in patients with persistent symptoms 4

Special Situations

• During late pregnancy: Increase fludrocortisone dose due to anti-mineralocorticoid effects of progesterone 1
• If essential hypertension develops: Reduce (but do not discontinue) fludrocortisone dose 4, 1
• In primary adrenal insufficiency (where both cortisol and aldosterone are deficient): Add glucocorticoid replacement with hydrocortisone 15-25 mg daily in divided doses, and restart fludrocortisone when hydrocortisone dose falls below 50 mg/day 4, 1

Medication Interactions to Avoid

The following medications interfere with fludrocortisone and should be avoided 1:

• Diuretics
• Acetazolamide
• NSAIDs
• Licorice (has mineralocorticoid activity)
• Grapefruit juice
• Drospirenone-containing contraceptives (may require fludrocortisone dose adjustment)

Alternative Management for Pseudohypoaldosteronism

Since the treatment differs fundamentally based on etiology 3:

• Type I pseudohypoaldosteronism: Potassium restriction, sodium bicarbonate, and loop diuretics (not fludrocortisone, as aldosterone resistance is present) 3
• Type II pseudohypoaldosteronism: Sodium restriction and thiazide diuretics 3
• Severe hyperkalemia in any form: May require potassium-binding resins 3

Annual Follow-Up

Regular monitoring should include 4:

• Assessment of quality of life, medication adherence, and self-management during illness
• Physical examination for signs of under- or over-replacement
• Serum electrolytes (sodium and potassium)
• Screening for associated autoimmune conditions if primary adrenal insufficiency is present 4