What is the treatment for adrenal insufficiency?

Treatment for Adrenal Insufficiency

The standard treatment for adrenal insufficiency consists of glucocorticoid replacement with hydrocortisone (15-25 mg daily in divided doses) and mineralocorticoid replacement with fludrocortisone (50-200 μg once daily) for primary adrenal insufficiency. 1

Glucocorticoid Replacement

Dosing and Administration

• Hydrocortisone is the preferred glucocorticoid replacement:

  • Total daily dose: 15-25 mg 1
  • Dosing schedule: Split doses with first dose immediately after waking, and last dose at least 6 hours before bedtime 1
  • Typical regimen: 2/3 of dose in morning, 1/3 in early afternoon 1
  • In children: 6-10 mg/m² of body surface area 1

• Alternative glucocorticoids:

  • Prednisone: 3-5 mg daily 2
  • Cortisone acetate: 18.75-31.25 mg daily 1
  • Modified-release hydrocortisone (Plenadren): Once-daily dosing, available in Europe 1

Severity-Based Treatment Approach

1. Mild symptoms (asymptomatic or G1):

   • Prednisone 5-10 mg daily or hydrocortisone 10-20 mg morning, 5-10 mg afternoon 1
   • Endocrine consultation recommended

2. Moderate symptoms (G2):

   • Initially higher doses (prednisone 20 mg daily or hydrocortisone 20-30 mg morning, 10-20 mg afternoon) 1
   • Taper to maintenance doses over 5-10 days

3. Severe symptoms/Adrenal crisis (G3-4):

   • Immediate IV hydrocortisone 100 mg bolus followed by 100-300 mg/day as continuous infusion or every 6 hours 1
   • Rapid IV isotonic saline (2-4 L with initial rate ~1 L/hour) 1
   • Taper to maintenance doses over 7-14 days after discharge 1

Mineralocorticoid Replacement

• For primary adrenal insufficiency only (not needed in secondary adrenal insufficiency) 1
• Fludrocortisone 50-200 μg once daily in the morning 1, 3
• Higher doses (up to 500 μg) may be needed in children, younger adults, or during pregnancy 1
• Monitor effectiveness through:
  • Blood pressure (including postural measurements)
  • Serum electrolytes
  • Presence of peripheral edema
  • Salt cravings 1

Adrenal Androgen Replacement

• Consider DHEA replacement (25 mg daily) in women with persistent fatigue or low libido despite optimized glucocorticoid and mineralocorticoid replacement 1
• Monitor DHEA-S, androstenedione, and testosterone levels
• Limited evidence for routine use 1

Special Situations

Adrenal Crisis Management

• Immediate IV/IM hydrocortisone 100 mg bolus followed by 100 mg every 6-8 hours 1
• Rapid IV isotonic saline infusion (initial rate ~1 L/hour) 1
• Identify and treat precipitating factors (infection, trauma, etc.) 1

Stress Dosing

• Minor illness/stress: Double or triple oral glucocorticoid dose 1
• Major surgery/severe illness: IV hydrocortisone 100 mg followed by 100-300 mg/day 1

Pregnancy

• May need increased hydrocortisone by 2.5-10 mg daily in third trimester 1
• Fludrocortisone dose often needs to be increased during late pregnancy 1
• During delivery: IV hydrocortisone 100 mg every 6 hours as needed 1
• Double oral dose for 24-48 hours postpartum 1

Patient Education and Monitoring

• All patients must have:
  • Medical alert bracelet/card identifying adrenal insufficiency 1
  • Education on stress dosing during illness 1
  • Emergency injectable hydrocortisone kit 4
  • Annual follow-up with assessment of weight, blood pressure, and electrolytes 1

Common Pitfalls and Caveats

• Mineralocorticoid under-replacement is common and can lead to recurrent adrenal crises 1
• Avoid medications that interact with fludrocortisone:
  • Diuretics, acetazolamide, NSAIDs (avoid)
  • Liquorice and grapefruit juice (potentiate mineralocorticoid effect) 1
• Always start glucocorticoids several days before thyroid hormone in patients with both adrenal and thyroid insufficiency 1
• Screen regularly for other autoimmune disorders, particularly thyroid disease 1
• Patients on chronic glucocorticoid therapy are at risk for adrenal insufficiency if medication is abruptly discontinued 2

The goal of treatment is to provide adequate hormone replacement while minimizing adverse effects, preventing adrenal crises, and optimizing quality of life.