What is the treatment for exogenous steroid-induced Cushing's syndrome?

Treatment of Exogenous Steroid-Induced Cushing's Syndrome

The primary treatment for exogenous steroid-induced Cushing's syndrome is gradual tapering and discontinuation of the offending steroid medication, while providing appropriate adrenal axis support during withdrawal. 1

Diagnosis and Recognition

• Exogenous steroid-induced Cushing's syndrome results from prolonged administration of glucocorticoids through oral, parenteral, or topical routes 2, 3
• Clinical features include cushingoid facies, central obesity, muscle wasting, hypertension, hyperglycemia, hypokalemia, osteoporosis, and increased susceptibility to infections 1
• Laboratory findings typically show suppressed endogenous cortisol production and ACTH levels due to negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis 1

Treatment Approach

1. Discontinuation Strategy

• Gradual tapering is essential rather than abrupt withdrawal to prevent adrenal insufficiency 4
• For oral steroids, implement alternate-day therapy during tapering to allow for re-establishment of more normal HPA axis activity on off-steroid days 4
• Tapering schedule should be individualized based on:
  • Duration of steroid use
  • Total cumulative dose
  • Potency of the steroid used
  • Underlying condition being treated 1, 4

2. Typical Tapering Protocol

• For long-term users (>3 months), reduce dose by approximately 10-20% every 1-2 weeks 4
• For high-dose, short-term users, more rapid tapering may be possible 4
• Morning dosing (before 9 am) is preferred to better mimic natural cortisol rhythm 4
• Monitor for signs of adrenal insufficiency during tapering (fatigue, weakness, hypotension, hypoglycemia) 1

3. Supportive Management During Tapering

• Provide stress-dose steroids during periods of illness, surgery, or significant stress 1
• Treat comorbidities associated with Cushing's syndrome:
  • Hypertension
  • Hyperglycemia/diabetes
  • Hypokalemia
  • Osteoporosis 1

4. For Topical Steroid-Induced Cushing's Syndrome

• Discontinue or switch to lower-potency topical steroids 3, 5
• Avoid occlusive dressings which increase absorption 5
• Limit application to affected areas only 3
• Consider non-steroidal alternatives for skin conditions when possible 5

5. For Severe Cases

• In cases of severe hypercortisolism with life-threatening complications, medical management with adrenostatic agents may be temporarily required while tapering 1, 6
• Options include:
  • Ketoconazole (400-1200 mg/day) - most commonly used due to relatively tolerable toxicity profile 1
  • Metyrapone (500 mg/day to 6 g/day) - rapid decrease in cortisol levels 1, 6
  • Osilodrostat (2-7 mg/day) - newer agent with high efficacy 1
  • Mitotane (250-500 mg/day up to 8 g/day) - slow onset but effective 1

Recovery of HPA Axis

• Recovery time for normal HPA activity is variable, depending on dose and duration of treatment 4
• May take weeks to months for full recovery 1, 4
• Monitor morning cortisol levels to assess recovery 1
• Continue education about the need for stress-dose steroids during recovery period 4

Prevention Strategies

• Use the lowest effective dose of steroids for the shortest duration possible 1
• Consider steroid-sparing agents when appropriate 1
• For topical steroids, limit quantity prescribed and avoid occlusive dressings 3, 5
• Patient education about proper use and potential side effects is essential 3

Common Pitfalls and Caveats

• Never abruptly discontinue steroids in patients with long-term use due to risk of adrenal crisis 4
• Patients may require stress-dose steroids for up to 12 months after discontinuation of long-term therapy 1, 4
• Patients should carry medical alert identification during and after tapering 1
• Symptoms of steroid withdrawal (fatigue, myalgia, arthralgia) may be confused with flare of underlying disease 1, 4
• Over-the-counter topical steroids can cause systemic effects if used excessively 3, 5