What is the preferred treatment between hydrocortisone and prednisolone for exogenous Cushing's syndrome?

Hydrocortisone vs. Prednisolone in Exogenous Cushing's Syndrome

Hydrocortisone is preferred over prednisolone for managing exogenous Cushing's syndrome due to its shorter half-life, better mimicking of natural cortisol rhythm, and reduced risk of iatrogenic Cushing's features. 1

Understanding Exogenous Cushing's Syndrome

Exogenous Cushing's syndrome results from supraphysiological exposure to external glucocorticoids (such as prednisone, prednisolone, dexamethasone) rather than endogenous overproduction. This condition is characterized by:

• Central obesity, moon facies, hirsutism, and reddish-purple stretch marks
• Metabolic abnormalities (hyperglycemia, hypertension)
• Increased risk of infections
• Neuropsychiatric symptoms
• Increased cardiovascular risk

Treatment Approach

First-line Treatment: Hydrocortisone

When transitioning from high-dose exogenous steroids causing Cushing's syndrome:

• Hydrocortisone 15-20 mg daily in divided doses (typically 2/3 in morning, 1/3 in early afternoon) 1
• Titrate to a maximum of 30 mg daily total dose based on symptoms
• Reduce maintenance dosing if symptoms of iatrogenic Cushing's syndrome persist

Why Hydrocortisone is Superior to Prednisolone:

1. Better Physiologic Profile:

   • Hydrocortisone allows for recreation of the natural diurnal rhythm of cortisol 1
   • Shorter half-life (8-12 hours) compared to prednisolone (12-36 hours)
   • Closer mimicking of natural cortisol production

2. Reduced Risk of Persistent Cushing's Features:

   • Lower risk of bruising, thin skin, edema, weight gain, hypertension, and hyperglycemia 1
   • Easier to titrate and adjust based on clinical response

3. Conversion Equivalence:

   • 20 mg of hydrocortisone is equivalent to 5 mg of prednisolone 1
   • This allows for more precise dosing when tapering

Monitoring and Dose Adjustment

• Assess for signs of persistent Cushing's features (bruising, thin skin, edema, weight gain)
• Monitor for symptoms of adrenal insufficiency (fatigue, weakness, hypotension)
• Adjust dose based on clinical response, aiming for the lowest effective dose
• Provide education on stress dosing for sick days and emergency situations

Special Considerations

Drug Interactions

• Be cautious when combining with azole antifungals (e.g., itraconazole) as this can increase the risk of exogenous Cushing's syndrome 1
• Methylprednisolone combined with oral itraconazole has a higher risk of exogenous Cushing's syndrome and adrenal insufficiency 1

Tapering Schedule

• Gradual tapering is essential to avoid adrenal crisis
• Never stop abruptly after long-term therapy 2
• Individualize tapering schedule based on duration of prior steroid exposure

Common Pitfalls to Avoid

1. Abrupt Discontinuation:

   • Always taper gradually to allow HPA axis recovery
   • Sudden withdrawal can precipitate adrenal crisis

2. Inadequate Patient Education:

   • Patients need clear instructions on stress dosing
   • Medical alert bracelet/card for adrenal insufficiency is recommended 1

3. Overlooking Comorbidities:

   • Continue to manage persistent metabolic abnormalities even after steroid adjustment
   • Screen for and treat osteoporosis, hypertension, and diabetes

4. Insufficient Monitoring:

   • Regular follow-up is essential to assess for both under-replacement and over-replacement

In conclusion, while both hydrocortisone and prednisolone can be used in managing exogenous Cushing's syndrome, hydrocortisone is preferred due to its physiologic profile, shorter half-life, and reduced risk of perpetuating Cushing's features. The goal is to provide adequate glucocorticoid coverage while minimizing adverse effects and allowing recovery of the HPA axis.