What is the treatment for adrenal insufficiency due to low cortisol levels?

Treatment for Adrenal Insufficiency Due to Low Cortisol Levels

The standard treatment for adrenal insufficiency is glucocorticoid replacement with hydrocortisone (15-25 mg daily) in divided doses, plus fludrocortisone (0.05-0.2 mg daily) for primary adrenal insufficiency. 1

Diagnosis Confirmation

Before initiating treatment, confirm adrenal insufficiency with:

• Morning serum cortisol and ACTH levels
• ACTH stimulation test if results are equivocal
• Distinguish between primary (low cortisol, high ACTH) and secondary (low cortisol, low/normal ACTH) adrenal insufficiency 2

Glucocorticoid Replacement

Primary Adrenal Insufficiency

• Hydrocortisone: 15-25 mg daily in divided doses
  • Typical regimen: 10 mg on waking, 5 mg at noon, 2.5 mg in late afternoon (16:00) 1
  • Alternative regimens: 15+5+5 mg, 10+5+5 mg, 10+5+2.5 mg, or 7.5+5+2.5 mg 1
• Cortisone acetate: 25-37.5 mg daily in divided doses (alternative to hydrocortisone) 1
• Prednisolone: 4-5 mg daily (only for selected patients with compliance issues or marked energy fluctuations) 1

Secondary Adrenal Insufficiency

• Similar glucocorticoid regimens as primary adrenal insufficiency
• No mineralocorticoid replacement needed 1

Mineralocorticoid Replacement (for Primary Adrenal Insufficiency Only)

• Fludrocortisone: 0.05-0.2 mg once daily upon awakening 1
• Higher doses (up to 0.5 mg daily) may be needed in children, younger adults, or during pregnancy 1
• Evaluate effectiveness by monitoring:
  • Blood pressure (sitting and standing)
  • Salt cravings
  • Presence of peripheral edema
  • Electrolytes (sodium and potassium) 1, 2

Dose Adjustments and Monitoring

Dose Titration

• Adjust based on clinical symptoms rather than laboratory values
• Signs of over-replacement: weight gain, insomnia, peripheral edema
• Signs of under-replacement: fatigue, nausea, poor appetite, weight loss, increased pigmentation 1

Special Situations

• Morning symptoms: Take first dose earlier and go back to sleep 1
• Night shift workers: Adjust schedule (e.g., 10 mg upon awakening before work) 1
• Drug interactions: Adjust dose when taking medications that affect hydrocortisone metabolism:
  • May need increased dose with: anti-epileptics, barbiturates, antituberculosis drugs, etomidate, topiramate
  • May need decreased dose with: grapefruit juice, licorice 1

Stress Dosing

Minor Illness (fever, cold)

• Double regular daily dose until recovery 2

Moderate Stress

• 2-3 times maintenance dose (e.g., hydrocortisone 20-30 mg morning, 10-20 mg afternoon)
• Taper back to maintenance over 5-10 days 1

Severe Stress/Adrenal Crisis

• Immediate IV hydrocortisone 100 mg or dexamethasone 4 mg
• IV normal saline (at least 2L)
• Taper to maintenance dose over 7-14 days 1, 2

Patient Education and Emergency Preparedness

All patients must:

• Wear medical alert identification (bracelet/card) 1, 2
• Carry emergency injectable hydrocortisone 2
• Understand "sick day rules" for stress dosing 2
• Consult with endocrinologist before surgery or procedures 1
• Eat unrestricted sodium but avoid potassium-containing salt substitutes 1

Pitfalls to Avoid

• Never delay treatment if adrenal crisis is suspected 2
• Always start corticosteroids before thyroid hormone in patients with multiple hormone deficiencies 2
• Avoid dexamethasone for long-term replacement (lacks mineralocorticoid activity) 1
• Avoid medications that interact with fludrocortisone: diuretics, acetazolamide, carbenoxolone, NSAIDs 1
• Don't rely on plasma ACTH and serum cortisol for dose adjustments during maintenance therapy 1
• Beware of under-replacement with mineralocorticoids, which can lead to recurrent adrenal crises 1

Newer Treatment Options

• Modified-release hydrocortisone (Plenadren) allows once-daily dosing but is still being evaluated 1
• Continuous subcutaneous hydrocortisone infusion may better mimic physiological cortisol patterns in selected cases 3, 4