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) plus fludrocortisone (0.05-0.2 mg daily) for primary adrenal insufficiency. 1, 2

Glucocorticoid Replacement

Hydrocortisone is the preferred glucocorticoid replacement for several reasons:

• It most closely mimics physiologic cortisol
• It provides both glucocorticoid and some mineralocorticoid effects
• Standard dosing is 15-25 mg daily 1, 3

Dosing Schedule:

• Three-dose regimen (preferred): 10 mg on awakening, 5 mg at noon, 2.5-5 mg in late afternoon (before 6 PM)
• Two-dose regimen (alternative): 15 mg on awakening, 5 mg in early afternoon 1

Monitoring:

• Clinical assessment is the primary method for dose adjustment
• Signs of over-replacement: weight gain, insomnia, peripheral edema
• Signs of under-replacement: fatigue, nausea, poor appetite, weight loss, increased pigmentation 1

Mineralocorticoid Replacement

For primary adrenal insufficiency, mineralocorticoid replacement is essential:

• Fludrocortisone: 0.05-0.2 mg once daily, typically taken upon awakening 1, 2
• Dose is adjusted based on:
  • Blood pressure (standing and supine)
  • Serum electrolytes (sodium and potassium)
  • Presence of peripheral edema
  • Salt cravings 1

Important considerations:

• Allow unrestricted sodium intake
• Avoid potassium-containing salt substitutes
• Under-replacement is common and may predispose to adrenal crises 1

Medication Interactions to Monitor

Drugs affecting hydrocortisone metabolism:

• Anti-epileptics/barbiturates (may need increased dose)
• Antituberculosis drugs (may need increased dose)
• Antifungal drugs (may need dose adjustment)
• Etomidate (may need increased dose)
• Topiramate (may need increased dose)
• Grapefruit juice (may need decreased dose)
• Liquorice (may need decreased dose) 1

Drugs affecting fludrocortisone:

• Diuretics (avoid)
• Acetazolamide (avoid)
• Carbenoxolone, licorice (avoid)
• NSAIDs (avoid)
• Drospirenone-containing contraceptives (may need increased dose) 1

Patient Education and Crisis Prevention

All patients must:

• Wear a medical alert bracelet/necklace
• Carry a steroid card
• Learn how to adjust doses during illness or stress
• Have emergency injectable hydrocortisone available 1, 3

Adrenal Crisis Management

For adrenal crisis (life-threatening emergency):

1. Immediate IV hydrocortisone 100 mg bolus 4
2. Follow with 100-300 mg/day as continuous infusion or divided doses every 6 hours
3. Rapid IV fluid resuscitation with isotonic saline (1L over first hour)
4. Treat precipitating conditions 1

Common Pitfalls to Avoid

1. Inadequate mineralocorticoid replacement - leads to salt cravings, postural hypotension, and increased risk of adrenal crisis
2. Evening dosing of hydrocortisone - can cause insomnia and disrupt circadian rhythm
3. Failure to adjust doses during illness - major cause of adrenal crisis
4. Relying on laboratory tests alone - clinical assessment is more important for dose adjustments
5. Overlooking drug interactions - can lead to under or over-replacement 1, 3

Adrenal insufficiency requires lifelong hormone replacement therapy, with careful attention to dose adjustments during times of illness or stress to prevent potentially fatal adrenal crisis.