What is the treatment for exogenous Cushing's syndrome?

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 providing appropriate supportive care for adrenal insufficiency. 1, 2

Understanding Exogenous Cushing's Syndrome

Exogenous Cushing's syndrome occurs due to prolonged exposure to synthetic glucocorticoids from external sources, most commonly prescribed medications. Unlike endogenous Cushing's syndrome (which results from overproduction of cortisol by the body), exogenous Cushing's requires a different management approach focused on addressing the iatrogenic cause.

Treatment Algorithm

Step 1: Identify and Address the Underlying Cause

• Confirm the source of exogenous glucocorticoid exposure (oral, injectable, topical, or inhaled)
• Review necessity of current glucocorticoid therapy with prescribing physician
• Consider alternative non-glucocorticoid therapies for the underlying condition when possible 1

Step 2: Implement Glucocorticoid Tapering

• Do not abruptly discontinue glucocorticoids as this may precipitate adrenal crisis 3
• Follow a structured tapering schedule based on:
  • Duration of prior glucocorticoid use
  • Current dose
  • Individual patient response
  • Underlying condition being treated

Tapering Protocol Example:

• For long-term users (>3 months): Reduce dose by approximately 10-20% every 1-2 weeks 3
• For high-dose short-term users: Consider more rapid tapering (25-50% reduction every few days)
• Morning administration is preferred to minimize HPA axis suppression 3

Step 3: Monitor for and Manage Complications

• Adrenal Insufficiency Management:

  • Provide stress-dose steroids during illness, surgery, or significant stress 2
  • Educate patient on signs/symptoms of adrenal insufficiency
  • Consider hydrocortisone replacement until HPA axis recovery

• Metabolic Complications:

  • Treat hypertension with mineralocorticoid receptor antagonists (spironolactone or eplerenone) 1
  • Manage hyperglycemia with appropriate glycemic control measures
  • Address dyslipidemia with dietary modifications and lipid-lowering therapy if needed

Step 4: Assess for HPA Axis Recovery

• Perform morning cortisol testing after glucocorticoid discontinuation
• Consider ACTH stimulation testing to evaluate adrenal function
• Continue physiologic replacement until HPA axis recovery is confirmed 2

Special Considerations

Drug Interactions

• Avoid concomitant use of medications that can potentiate glucocorticoid effects:
  • Itraconazole and other azole antifungals can significantly increase risk of Cushing's syndrome when combined with glucocorticoids 4
  • Inhaled fluticasone or budesonide combined with itraconazole can cause exogenous Cushing's syndrome 4

Monitoring Parameters

• Blood pressure
• Blood glucose
• Electrolytes (particularly potassium)
• Bone density
• Weight
• Psychological status

Common Pitfalls to Avoid

1. Abrupt discontinuation of glucocorticoids, which can precipitate adrenal crisis 3, 2

2. Failure to recognize hidden sources of glucocorticoids (topical preparations, intra-articular injections, herbal supplements) 5

3. Overlooking concurrent endogenous Cushing's syndrome in patients with history of exogenous glucocorticoid use 6

4. Inadequate patient education about symptoms of adrenal insufficiency during tapering

5. Insufficient stress dosing during intercurrent illness or procedures

Duration of Recovery

Recovery of the HPA axis after discontinuation of exogenous glucocorticoids may take months to years depending on:

• Duration of prior glucocorticoid therapy
• Cumulative dose
• Individual factors

Patients may require physiologic glucocorticoid replacement during this recovery period to prevent symptoms of adrenal insufficiency 2.