Treatment Strategy for Exogenous Cushing's Syndrome
The primary treatment for exogenous Cushing's syndrome is immediate discontinuation of the causative glucocorticoid if medically feasible, followed by gradual tapering to prevent adrenal insufficiency. 1, 2
Initial Management: Discontinuation and Tapering
Stop the exogenous glucocorticoid source immediately if possible. 1 This includes:
- Oral glucocorticoids 1
- Injectable steroids 1
- Inhaled corticosteroids 1
- Topical glucocorticoid preparations 1
Implement a gradual taper rather than abrupt cessation to avoid precipitating adrenal crisis, as prolonged exogenous glucocorticoid use suppresses the hypothalamic-pituitary-adrenal axis. 2 The tapering schedule depends on duration and dose of prior glucocorticoid exposure.
Critical Monitoring During Tapering
Monitor closely for signs of adrenal insufficiency throughout the tapering process, including: 2
Alternative Medication Strategies
For patients who cannot discontinue glucocorticoids due to underlying medical conditions:
Switch to lower-dose inhaled steroids or alternative non-steroidal medications for the underlying condition when possible. 2
Use spacer devices with inhaled corticosteroids to reduce systemic absorption. 2
Rinse mouth thoroughly after inhaled steroid use to decrease the swallowed portion and minimize systemic exposure. 2
Drug Interaction Prevention
Avoid concomitant use of azole antifungals (itraconazole, voriconazole) with inhaled budesonide or fluticasone, as this combination significantly increases risk of exogenous Cushing's syndrome through CYP3A4 inhibition. 2
Avoid methylprednisolone when combined with oral itraconazole due to heightened risk of exogenous Cushing's syndrome and subsequent adrenal insufficiency. 2
Management of Complications
Hypertension
Use spironolactone or eplerenone for hypertension management, as these mineralocorticoid receptor antagonists block the effects of excess cortisol on mineralocorticoid receptors. 2
Hyperglycemia
Implement appropriate glucose-lowering therapy, with consideration of GLP-1 receptor agonists or DPP-4 inhibitors if pasireotide is being used concurrently. 2
Severe Cases Requiring Pharmacologic Intervention
For severe exogenous Cushing's syndrome with life-threatening complications where glucocorticoids cannot be discontinued:
Consider mifepristone (glucocorticoid receptor blocker) for severe hypercortisolism, though this requires careful monitoring as cortisol levels remain elevated and only clinical features can assess treatment response. 2
Consider medications that block cortisol synthesis (ketoconazole, metyrapone) for severe cases with complications. 2
Ongoing Monitoring
Monitor for resolution of Cushingoid features, including: 2
- Weight changes 2
- Blood pressure normalization 2
- Glucose levels 2
- Physical stigmata (facial plethora, striae, easy bruising) 2
Important Clinical Pitfall
Do not assume all Cushingoid features are due to exogenous glucocorticoids alone. Rare cases of co-occurrence of exogenous and endogenous Cushing's syndrome have been reported. 3 If Cushingoid features persist after complete cessation of exogenous glucocorticoids for an adequate period (typically several months to one year), investigate for endogenous Cushing's syndrome with appropriate biochemical testing. 3