What is the primary treatment for adrenal insufficiency?

Treatment of Adrenal Insufficiency

The primary treatment for adrenal insufficiency is glucocorticoid replacement with hydrocortisone (15-25 mg daily in divided doses) combined with mineralocorticoid replacement using fludrocortisone (50-200 μg daily) for patients with primary adrenal insufficiency. 1, 2

Glucocorticoid Replacement

Standard Dosing Regimen

• Hydrocortisone: 15-25 mg daily in divided doses
  • Three-dose regimen: 10 mg (morning) + 5 mg (noon) + 2.5-5 mg (afternoon)
  • Two-dose regimen: 15-20 mg (morning) + 5-10 mg (early afternoon)
• Alternative: Cortisone acetate 25-37.5 mg daily in divided doses
• Alternative: Prednisolone 4-5 mg daily (only if compliance issues or intolerance to hydrocortisone) 1

Administration Timing

• Larger morning dose upon waking (mimics natural cortisol peak)
• Last dose at least 6 hours before bedtime to avoid sleep disturbance
• Modified-release hydrocortisone (Plenadren) allows once-daily dosing but is still being evaluated 1

Mineralocorticoid Replacement

• Fludrocortisone 50-200 μg daily in a single morning dose 1, 3
• Higher doses (up to 500 μg daily) sometimes needed in:
  • Children and younger adults
  • Last trimester of pregnancy (when progesterone counteracts mineralocorticoids) 1
• Indicated for primary adrenal insufficiency (Addison's disease) and salt-losing adrenogenital syndrome 3

Monitoring Treatment Efficacy

Clinical Parameters

• Blood pressure (supine and standing to check for postural hypotension)
• Weight (loss suggests insufficient replacement)
• Peripheral edema (suggests over-replacement)
• Salt cravings (suggests under-replacement)
• Overall energy levels and well-being 1, 2

Laboratory Parameters

• Serum electrolytes (sodium, potassium)
• Plasma renin activity (for mineralocorticoid adequacy) 2

Stress Dosing Protocol

Minor Illness/Stress

• Double or triple usual daily glucocorticoid dose 2

Moderate Stress

• Hydrocortisone 50-75 mg/day in divided doses 2

Severe Stress/Adrenal Crisis

• Hydrocortisone 100 mg IV/IM immediately
• Continue with 100-300 mg/day as continuous infusion or divided doses every 6 hours
• Fluid resuscitation with 3-4 L isotonic saline (initial rate ~1 L/hour)
• Monitor hemodynamic parameters and electrolytes 1, 2

Special Situations

Surgery

• Major surgery: 100 mg hydrocortisone IM before anesthesia, continue 100 mg IM every 6 hours until oral intake resumes
• Minor surgery: 100 mg hydrocortisone IM before anesthesia, double oral dose for 24 hours afterward 1

Pregnancy and Delivery

• 100 mg hydrocortisone IM at onset of labor
• Double oral dose for 24-48 hours after delivery 1

Physical Activity

• Extra 5 mg hydrocortisone before intense exercise (e.g., marathon)
• Additional fluid and salt intake during hot conditions or intense activity 1

Patient Education and Emergency Preparedness

• All patients should:
  • Wear medical alert identification
  • Carry a steroid alert card
  • Have an emergency hydrocortisone injection kit
  • Receive education on managing daily medications and illness 2

Common Pitfalls and Caveats

• Under-replacement of mineralocorticoids is common and may be compensated by over-replacement of glucocorticoids 1
• Medications that can interact with fludrocortisone (require dose adjustments):
  • Diuretics
  • Acetazolamide
  • NSAIDs
  • Drospirenone-containing contraceptives 1
• Medications that can interact with hydrocortisone:
  • Anti-epilepsy drugs/barbiturates (may need more hydrocortisone)
  • Antituberculosis drugs (may need more hydrocortisone)
  • Grapefruit juice (may need less hydrocortisone)
  • Liquorice (may need less hydrocortisone) 1
• Essential hypertension should be treated with vasodilators, not by stopping mineralocorticoid replacement (though dose reduction may be considered) 1
• Adrenal crisis can be precipitated by vomiting, diarrhea, infections, surgery, injury, or non-compliance 1, 4

Proper replacement therapy is critical as recent data shows that patients with adrenal insufficiency have impaired quality of life, increased morbidity, and reduced life expectancy despite conventional treatment 5, 6. This appears to be due to both increased exposure to cortisol and insufficient cortisol coverage during stress-related events 5.