What is the first line treatment for adrenal insufficiency?

First-Line Treatment for Adrenal Insufficiency

The first-line treatment for adrenal insufficiency is hydrocortisone (15-25 mg daily) in divided doses, combined with fludrocortisone (50-200 μg daily) for patients with primary adrenal insufficiency. 1

Glucocorticoid Replacement

Glucocorticoid replacement is the cornerstone of adrenal insufficiency treatment:

• Hydrocortisone is the preferred glucocorticoid replacement:

  • Typical dosage: 15-25 mg/day 1, 2
  • Standard regimen: Three divided doses (e.g., 10 mg on awakening, 5 mg at noon, 2.5 mg in late afternoon) 1
  • Two-dose regimen alternative: 15 mg + 5 mg or 10 mg + 10 mg 1

• Cortisone acetate is an alternative:

  • Typical dosage: 25-37.5 mg/day
  • Requires activation to hydrocortisone by hepatic 11β-hydroxysteroid dehydrogenase type 1 1

• Prednisolone (3-5 mg daily) may be considered in select cases:

  • For patients with compliance issues
  • For those experiencing marked fluctuations in energy levels
  • When hydrocortisone/cortisone acetate is not tolerated 1, 2

Mineralocorticoid Replacement

For primary adrenal insufficiency only (not needed in secondary adrenal insufficiency):

• Fludrocortisone: 50-200 μg once daily upon awakening 1
  • Higher doses (up to 500 μg daily) sometimes needed in children, younger adults, or during pregnancy 1
  • Dose should be adjusted based on:
    • Blood pressure (supine and standing)
    • Presence of peripheral edema
    • Serum potassium levels
    • Salt cravings or lightheadedness

Monitoring Treatment Efficacy

Clinical assessment is the primary method for monitoring glucocorticoid replacement:

• Signs of over-replacement: Weight gain, insomnia, peripheral edema
• Signs of under-replacement: Lethargy, nausea, poor appetite, weight loss, increased pigmentation 1

Fine-tuning of dosage should be based on:

• Patient's weight
• Energy levels throughout the day
• Mental concentration
• Daytime somnolence
• Changes in pigmentation
• Sleep patterns 1

Special Considerations

1. Morning symptoms: For patients with nausea/vomiting in the morning, consider waking earlier to take the first dose, then returning to sleep 1

2. Medication interactions:

   • Drugs that may increase hydrocortisone requirements: Anti-epileptics, barbiturates, antituberculosis drugs, etomidate, topiramate 1
   • Substances that may decrease hydrocortisone requirements: Grapefruit juice, licorice 1
   • Drugs to avoid with fludrocortisone: Diuretics, acetazolamide, carbenoxolone, NSAIDs 1

3. Adrenal androgen replacement:

   • Consider DHEA (25 mg daily) for women with persistent low libido or energy levels despite optimized glucocorticoid and mineralocorticoid replacement 1
   • Monitor DHEAS, androstenedione, and testosterone levels 1

4. Patient education:

   • Patients should carry a steroid card and wear a medical alert bracelet 1
   • Instruction on stress dosing during illness is essential to prevent adrenal crisis 1, 2
   • Unrestricted sodium intake is recommended; avoid potassium-containing salt substitutes 1

Adrenal Crisis Prevention

All patients with adrenal insufficiency should:

• Be educated about increasing glucocorticoid doses during illness or stress
• Have injectable hydrocortisone available for emergency use
• Be trained in parenteral hydrocortisone administration 2, 3

Failure to provide adequate glucocorticoid coverage during stress can lead to life-threatening adrenal crisis, characterized by hypotension, shock, hyponatremia, and altered mental status 2.