What can be substituted for hydrocortisone (cortisol) in treating adrenal insufficiency if it's not available?

Substituting Hydrocortisone for Adrenal Insufficiency

When hydrocortisone is not available for adrenal insufficiency, prednisone or prednisolone should be substituted as the glucocorticoid component, combined with fludrocortisone for mineralocorticoid replacement in primary adrenal insufficiency. 1, 2

Glucocorticoid Substitution Options

Oral Replacement Therapy

• Prednisone/Prednisolone: 5-10 mg daily can be used as a substitute for hydrocortisone 10-30 mg daily 1
  • Typically given in divided doses to mimic natural cortisol rhythm
  • Longer half-life than hydrocortisone (biological half-life of 12-36 hours vs 8-12 hours)
  • More cost-effective than hydrocortisone in many healthcare systems

Important Considerations with Prednisolone

• Recent evidence suggests potential concerns with prednisolone in primary adrenal insufficiency:
  • Higher mortality compared to hydrocortisone in primary adrenal insufficiency (adjusted HR 2.92 vs 1.90) 3
  • Associated with worse lipid profiles, particularly higher total and LDL cholesterol levels 4
  • No significant mortality difference observed in secondary adrenal insufficiency 3

Mineralocorticoid Replacement

• Fludrocortisone: Required for primary adrenal insufficiency (not typically needed in secondary adrenal insufficiency) 2
  • Standard dose: 0.1 mg daily (range 0.05-0.2 mg) 2
  • Should be administered alongside glucocorticoid replacement 2
  • Dosage may need adjustment based on blood pressure, electrolytes, and edema 1

Dosing Guidelines

For Routine Maintenance:

1. Prednisolone: 5-10 mg daily in divided doses (typically 2/3 in morning, 1/3 in afternoon) 1, 3
2. Fludrocortisone: 0.1 mg daily (for primary adrenal insufficiency) 2

For Stress Dosing (during illness or surgery):

• Double or triple the maintenance glucocorticoid dose during minor illness 1
• For severe stress or adrenal crisis:
  • IV prednisolone or dexamethasone may be used if hydrocortisone is unavailable
  • Note that continuous IV hydrocortisone infusion (200 mg/24h) would be ideal during major stress 5

Monitoring and Adjustment

• Monitor for signs of over-replacement:

  • Weight gain, hypertension, edema, glucose intolerance
  • Cushingoid features (moon face, striae, central obesity)

• Monitor for signs of under-replacement:

  • Fatigue, weakness, nausea, hypotension, electrolyte abnormalities
  • Risk of adrenal crisis during stress

• Regular laboratory monitoring:

  • Electrolytes (particularly in primary adrenal insufficiency)
  • Lipid profile (especially with prednisolone) 4
  • Blood pressure

Pitfalls and Caveats

• Dosing challenges: Current standard treatment regimens often result in non-physiological cortisol levels with periods of over- and under-replacement 6, 7
• Mortality risk: Adrenal insufficiency is associated with increased mortality despite treatment 7
• Patient education: All patients require education on stress dosing, emergency injectable steroids, and medical alert identification 1
• Lipid monitoring: More vigilant monitoring of lipid profiles may be needed with prednisolone replacement 4

Remember that the goal of therapy is to mimic the natural cortisol rhythm as closely as possible while avoiding both over- and under-replacement, which can be challenging with currently available oral formulations 6, 7.