Treatment of Exogenous Cushing's Syndrome
The primary treatment for exogenous Cushing's syndrome is gradual tapering and discontinuation of the causative glucocorticoid medication, while carefully monitoring for adrenal insufficiency and disease reactivation. 1, 2
Understanding Exogenous Cushing's Syndrome
Exogenous Cushing's syndrome results from prolonged exposure to external (iatrogenic) glucocorticoid medications used to treat various conditions. It is the most common form of Cushing's syndrome and presents with:
- Cushingoid features: moon face, buffalo hump, central obesity
- Metabolic complications: hyperglycemia, hypertension
- Skin changes: thin fragile skin, petechiae, ecchymoses
- Neuropsychiatric symptoms: mood disorders, cognitive changes
- Suppression of the hypothalamic-pituitary-adrenal (HPA) axis 3, 4
Treatment Algorithm
Step 1: Identify and Address the Underlying Cause
- Determine which exogenous glucocorticoid is causing the syndrome
- Evaluate if the medication can be discontinued or replaced with a non-glucocorticoid alternative
- Consider if the dose can be reduced while maintaining disease control 1, 2
Step 2: Implement Gradual Tapering Protocol
- Never abruptly discontinue glucocorticoids due to risk of adrenal insufficiency
- Tapering schedule depends on:
- Duration of prior glucocorticoid use
- Dose of glucocorticoid
- Individual patient response
- Underlying disease activity 2
Step 3: Monitor for Complications During Withdrawal
Three major complications require monitoring:
- Adrenal insufficiency: fatigue, weakness, hypotension, hypoglycemia
- Reactivation of underlying disease: return of symptoms of the condition being treated
- Steroid withdrawal syndrome: myalgia, arthralgia, lethargy, depression 2
Step 4: Manage Comorbidities
- Treat hypertension with mineralocorticoid receptor antagonists (spironolactone or eplerenone) as first-line agents
- Address hyperglycemia with appropriate diabetic medications
- Consider bone protection strategies for steroid-induced osteoporosis
- Manage dyslipidemia if present 1
Practical Tapering Approaches
For long-term glucocorticoid use (>3 months):
- Reduce dose by 10-20% every 1-2 weeks if on high doses
- Once at physiologic dose (equivalent to prednisone 5-7.5 mg/day):
- Switch to once-daily morning dosing
- Reduce by 1 mg every 2-4 weeks
- Consider alternate-day dosing before complete discontinuation 2
Monitoring During Tapering
- Regular clinical assessment for signs of adrenal insufficiency
- Morning cortisol levels to assess HPA axis recovery
- ACTH stimulation test when approaching physiologic doses
- Blood pressure monitoring
- Blood glucose monitoring in diabetic patients
- Assessment of underlying disease activity 1, 2
Special Considerations
- Acute complications: For severe psychosis or other life-threatening complications of hypercortisolism, more rapid dose reduction may be needed with close monitoring 5
- Concomitant medications: Avoid medications that can potentiate glucocorticoid effects, such as itraconazole and other azole antifungals 1
- Recovery time: The HPA axis may take months to years to fully recover after prolonged glucocorticoid use 2
- Stress dosing: During the recovery period, patients may require stress-dose steroids during illness, surgery, or other stressful events 1
Common Pitfalls to Avoid
- Tapering too quickly, which can precipitate adrenal crisis
- Failing to educate patients about signs of adrenal insufficiency
- Not providing patients with emergency glucocorticoids and instructions for use
- Overlooking the need for stress dosing during intercurrent illness
- Inadequate monitoring of the underlying condition being treated with glucocorticoids 2
By following this systematic approach to tapering exogenous glucocorticoids while carefully monitoring for complications, patients with exogenous Cushing's syndrome can be safely managed to minimize both the effects of hypercortisolism and the risks associated with glucocorticoid withdrawal.