What is the appropriate use and dosage of Aldosterone (a steroid hormone) for treating hormonal imbalances?

Aldosterone: Appropriate Use and Dosage for Hormonal Imbalances

Aldosterone antagonists (mineralocorticoid receptor antagonists) are the treatment of choice for primary aldosteronism and should be initiated at 12.5-25 mg daily of spironolactone with careful monitoring of potassium and renal function. The management depends on whether the condition is unilateral or bilateral, with surgical options for unilateral disease and medical therapy for bilateral disease.

Diagnosis and Evaluation of Aldosterone Excess

Before initiating treatment, proper diagnosis is essential:

• Measure plasma aldosterone concentration and plasma renin activity
• Calculate aldosterone:renin ratio (ARR) - a cutoff value of 30 is used when plasma aldosterone is reported in ng/dL and plasma renin activity in ng/mL/h 1
• Plasma aldosterone concentration should be at least 10 ng/dL to interpret the test as positive 1
• Ensure patients have:
  • Unrestricted salt intake
  • Normal serum potassium
  • No mineralocorticoid receptor antagonists for at least 4 weeks before testing 1

Confirmatory testing is generally required (intravenous saline suppression test or oral salt-loading test) 1.

Treatment Approach

For Unilateral Aldosterone Excess

1. Refer for adrenal venous sampling to determine if unilateral or bilateral 1
2. If unilateral, refer for laparoscopic adrenalectomy, which:
   • Improves blood pressure in virtually 100% of patients
   • Results in complete cure of hypertension in about 50% 1

For Bilateral Aldosterone Excess or Non-Surgical Candidates

Medical therapy with mineralocorticoid receptor antagonists is the treatment of choice:

1. First-line agent: Spironolactone

   • Initial dose: 12.5-25 mg daily 1, 2, 3
   • For those with concerns about hyperkalemia or marginal renal function (eGFR 30-49 mL/min/1.73 m²), consider every-other-day dosing 1
   • Maintenance dose: Can be increased to 25-50 mg daily if needed 1, 2
   • Maximum dose: 100-400 mg daily for primary hyperaldosteronism 3

2. Alternative: Eplerenone

   • More selective mineralocorticoid receptor antagonist with fewer anti-androgenic side effects 4, 5
   • Initial dose: 25 mg once daily 1
   • Maintenance dose: Can be increased to 50 mg once daily 1

Monitoring Protocol

• Check potassium and renal function within 2-3 days after initiation 1, 2
• Recheck at 7 days 1, 2
• Monthly monitoring for first 3 months, then every 3 months if stable 2
• Target serum potassium: 4.0-5.0 mEq/L 2

Special Considerations

Women of Reproductive Age

• Spironolactone has anti-androgenic effects that may cause menstrual irregularities, breast tenderness, and hirsutism 1
• Consider eplerenone as an alternative in women of reproductive age 4, 5

Pregnancy

• Mineralocorticoid antagonists are generally contraindicated in pregnancy
• For pregnant women with primary aldosteronism, consider other antihypertensive medications 1

Adrenal Insufficiency

• In patients with primary adrenal insufficiency who may need aldosterone replacement:
  • Fludrocortisone is the mineralocorticoid of choice (not aldosterone directly)
  • Typical dose: 0.05-0.2 mg daily 1
  • Dose may need to be increased during pregnancy due to progesterone's anti-mineralocorticoid effects 1

Potential Adverse Effects and Precautions

• Hyperkalemia: Most serious risk, especially with:

  • Renal insufficiency (creatinine >2.5 mg/dL in men or >2.0 mg/dL in women)
  • Baseline potassium >5.0 mEq/L
  • Concomitant use of potassium supplements, ACE inhibitors, or ARBs 1, 2

• Gynecomastia and sexual dysfunction: More common with spironolactone than eplerenone 4, 5

• Menstrual irregularities: May occur with spironolactone 1

• Drug interactions: Avoid NSAIDs which can worsen renal function and increase hyperkalemia risk 2

Common Pitfalls to Avoid

1. Failing to discontinue potassium supplements when initiating therapy 2

2. Not instructing patients to temporarily stop the medication during episodes of diarrhea, vomiting, or dehydration 2

3. Missing the diagnosis of primary aldosteronism in resistant hypertension cases 6, 7

4. Inadequate monitoring of potassium and renal function after initiation 1, 2

5. Using high doses of spironolactone when lower doses may be effective with fewer side effects 2

Treating primary aldosteronism, either with mineralocorticoid receptor antagonists or unilateral adrenalectomy when indicated, resolves hypokalemia, lowers blood pressure, reduces the number of antihypertensive medications required, and improves parameters of impaired cardiac and kidney function 1.