Management of Exogenous Cushing's Syndrome
The primary treatment for exogenous Cushing's syndrome is gradual tapering of the causative glucocorticoid medication rather than abrupt discontinuation, which can lead to adrenal insufficiency. 1
Understanding Exogenous Cushing's Syndrome
Exogenous Cushing's syndrome occurs when patients are exposed to excessive amounts of external glucocorticoids (such as prednisone, prednisolone, or other corticosteroids). This is the most common cause of Cushing's syndrome, characterized by:
- Obesity with central fat distribution
- Thinning of skin with easy bruisability
- Muscle wasting and weakness
- Hypertension
- Glucose intolerance/diabetes
- Osteoporosis
- Electrolyte imbalances
- Neuropsychiatric manifestations 1, 2
Treatment Algorithm
1. Gradual Tapering of Exogenous Glucocorticoids
- Never discontinue glucocorticoids abruptly - this can precipitate adrenal insufficiency due to HPA axis suppression 1
- Morning administration is preferred - administer before 9 AM to minimize adrenal suppression by mimicking natural cortisol rhythm 1
- Tapering schedule:
- Reduce dose in small increments at appropriate time intervals
- Continue until reaching the lowest effective dose that maintains clinical response
- For long-term therapy, consider alternate-day therapy (twice the usual daily dose given every other morning) 1
2. Managing Withdrawal Symptoms
Steroid withdrawal syndrome may occur despite acceptable cortisol levels and can manifest with symptoms similar to adrenal insufficiency:
- Fatigue, weakness, nausea, vomiting, hypotension
- Arthralgias, myalgias, fever
- Psychiatric symptoms 3
Management approach:
- Temporarily increase glucocorticoid dose if withdrawal symptoms occur
- Gradually taper again more slowly
- The syndrome is typically self-limiting (median duration ~10 months) 3
3. Monitoring During Tapering
- Regular assessment of clinical status for disease exacerbations
- Monitor for signs of adrenal insufficiency
- Adjust dosing during stressful situations (may require temporary dose increase) 1
4. Addressing Complications
- Hypertension: Mineralocorticoid receptor antagonists (spironolactone, eplerenone) are the cornerstone of antihypertensive therapy 4
- Glucose intolerance: Monitor blood glucose levels and adjust antidiabetic medications as needed
- Osteoporosis: Consider bone density assessment and appropriate therapy
- Electrolyte imbalances: Monitor and correct as needed 4, 2
Special Considerations
Alternate Day Therapy
For patients requiring long-term glucocorticoid treatment, consider alternate day therapy which:
- Provides therapeutic benefits while minimizing adverse effects
- Allows partial recovery of HPA axis function on off-days
- Reduces risk of cushingoid features, growth suppression, and adrenal suppression 1
Identifying Concurrent Endogenous Cushing's Syndrome
In rare cases, patients may have both exogenous and endogenous Cushing's syndrome. Consider this possibility if:
- Cushingoid features persist despite cessation of exogenous glucocorticoids for extended periods
- Additional testing is warranted in such cases (24-hour urinary free cortisol, overnight dexamethasone suppression test, ACTH levels) 5
Common Pitfalls to Avoid
- Abrupt discontinuation of glucocorticoids, which can precipitate adrenal crisis
- Failure to recognize steroid withdrawal syndrome as distinct from disease relapse
- Inadequate patient education about the importance of adherence to tapering schedule
- Not providing stress-dose instructions for illness or surgery during and after tapering
- Missing concurrent endogenous Cushing's syndrome in patients with persistent symptoms after exogenous steroid discontinuation 1, 5, 3
By following this approach, most patients with exogenous Cushing's syndrome can be successfully managed with gradual resolution of symptoms and recovery of normal HPA axis function.