What is the recommended treatment for adrenal insufficiency using Cortef (hydrocortisone)?

Hydrocortisone (Cortef) Treatment for Adrenal Insufficiency

For patients with primary adrenal insufficiency, the recommended treatment is 15-25 mg of hydrocortisone (Cortef) daily in split doses, with the first dose immediately after waking and the last dose not less than 6 hours before bedtime. 1

Dosing Regimen

Glucocorticoid Replacement

• Total daily dose: 15-25 mg of hydrocortisone (Cortef)
• Optimal dosing schedule: Three divided doses
  • Morning dose (immediately upon waking): 10 mg
  • Midday dose (around noon): 5 mg
  • Afternoon dose (around 4 PM): 2.5-5 mg
• Alternative two-dose regimen:
  • Morning: 15 mg
  • Early afternoon: 5 mg

The three-dose regimen (10+5+2.5 mg) better mimics the natural cortisol rhythm and provides more physiological coverage throughout the day 1.

Mineralocorticoid Replacement

• Most patients with primary adrenal insufficiency should also take 50-200 μg fludrocortisone (Florinef) as a single daily dose 1
• Not required for secondary adrenal insufficiency (when ACTH deficiency is the cause)

Dose Adjustments

Special Situations Requiring Dose Modification:

• Morning symptoms: For patients with morning nausea or lack of appetite, taking the first dose earlier (waking up, taking medication, then going back to sleep) may help relieve symptoms 1
• Night shift workers: Adjust schedule according to work pattern (e.g., 10 mg upon awakening before going to work) 1
• Stress doses: Increase hydrocortisone during:
  • Fever/illness: Double or triple the usual daily dose
  • Surgery/invasive procedures: IV or IM hydrocortisone required
  • Pregnancy: Small adjustments may be needed, particularly in the third trimester 1

Drug Interactions Requiring Dose Adjustments:

• May need increased hydrocortisone doses with:

  • Anti-epilepsy medications/barbiturates
  • Antituberculosis drugs
  • Etomidate
  • Topiramate 1

• May need decreased hydrocortisone doses with:

  • Grapefruit juice
  • Liquorice 1

Monitoring and Follow-up

• Annual clinical review with assessment of:
  • Overall health and well-being
  • Weight
  • Blood pressure (both lying and standing)
  • Serum electrolytes 1
• Consider serum or salivary cortisol day curve monitoring to guide dosing in cases of suspected malabsorption 1
• Monitor for development of other autoimmune disorders, particularly hypothyroidism 1
• Bone mineral density assessment every 3-5 years 1

Important Precautions

• All patients should:
  • Wear medical alert identification
  • Carry a steroid alert card
  • Have supplies for self-injection of parenteral hydrocortisone for emergencies 1
• Adrenal crisis should be treated immediately with 100 mg IV/IM hydrocortisone followed by 100 mg every 6-8 hours until recovered, along with isotonic saline 1
• Patients should take salt and salty foods freely and avoid potassium-containing salt substitutes 1
• Avoid dexamethasone for routine replacement therapy 1

Common Pitfalls

1. Under-replacement: Watch for symptoms like fatigue, nausea, poor appetite, weight loss, and increased pigmentation
2. Over-replacement: Watch for weight gain, insomnia, and peripheral edema
3. Inadequate stress dosing: Failure to increase doses during illness is a common cause of adrenal crisis
4. Timing errors: Taking the last dose too close to bedtime can cause insomnia
5. Missing mineralocorticoid replacement: Under-replacement is common and sometimes compensated by over-replacement with glucocorticoids 1

Hydrocortisone (Cortef) is the preferred glucocorticoid for replacement therapy as it most closely mimics natural cortisol and has both glucocorticoid and mineralocorticoid properties 2. While modified-release hydrocortisone formulations are being developed to better mimic physiological cortisol patterns, conventional immediate-release tablets remain the standard of care when properly dosed 1.