How is exogenous Cushing syndrome treated?

Treatment of Exogenous Cushing Syndrome

The primary treatment for exogenous Cushing syndrome is immediate discontinuation of the causative glucocorticoid if medically feasible, followed by gradual tapering to prevent adrenal insufficiency. 1

Initial Management: Source Identification and Discontinuation

The first critical step is identifying and stopping all sources of exogenous glucocorticoids 2, 1:

• Oral glucocorticoids (prednisone, dexamethasone, methylprednisolone) 1
• Injectable steroids (intra-articular, intramuscular, epidural) 1
• Inhaled corticosteroids (budesonide, fluticasone) 1
• Topical glucocorticoid preparations (high-potency creams, ointments) 1

Critical caveat: Abrupt discontinuation can precipitate life-threatening adrenal crisis, so gradual tapering is mandatory unless the patient has only received short-term therapy (<3 weeks). 1

Glucocorticoid Tapering Strategy

After confirming the diagnosis is exogenous (not endogenous hypercortisolism), implement a structured taper 1:

• Reduce the glucocorticoid dose gradually over weeks to months, depending on duration of prior use 1
• Monitor closely for adrenal insufficiency symptoms: fatigue, weakness, nausea, hypotension, and hypoglycemia 1
• Consider morning cortisol levels to assess HPA axis recovery during the taper 1

Drug Interaction Management

Avoid specific high-risk combinations that exacerbate exogenous Cushing syndrome 1:

• Do not combine azole antifungals (itraconazole, voriconazole) with inhaled budesonide or fluticasone, as this significantly increases systemic glucocorticoid exposure 1
• Avoid methylprednisolone with oral itraconazole due to heightened risk of Cushing syndrome followed by adrenal insufficiency 1

Management of Complications

Hypertension

Use mineralocorticoid receptor antagonists as first-line therapy 2, 1:

• Spironolactone or eplerenone block the mineralocorticoid effects of excess cortisol on renal sodium absorption 2, 1
• This addresses the primary mechanism of glucocorticoid-induced hypertension 2

Hyperglycemia

• Initiate appropriate glucose-lowering therapy 1
• Consider GLP-1 receptor agonists or DPP-4 inhibitors, particularly if pasireotide is being used for any reason 1

Hypokalemia

• Provide potassium supplementation as needed 3
• Mineralocorticoid receptor antagonists also help correct this 1

Severe Cases Requiring Pharmacologic Intervention

For patients with severe hypercortisolism who cannot immediately discontinue glucocorticoids due to underlying disease requirements 1:

Mifepristone (glucocorticoid receptor blocker) can be considered 1:

• Requires careful monitoring as cortisol levels remain elevated 1
• Only clinical features (not laboratory values) can assess treatment response 1

Cortisol synthesis inhibitors (ketoconazole, metyrapone) may be used for severe cases with complications 1:

• These are typically reserved for endogenous Cushing syndrome but can be considered in exceptional exogenous cases where discontinuation is impossible 1

Special Considerations for Inhaled Corticosteroids

When the source is inhaled steroids 1:

• Switch to lower-dose inhaled steroids or alternative medications for the underlying respiratory condition 1
• Use spacer devices with inhaled steroids to reduce systemic absorption 1
• Rinse mouth thoroughly after each inhaled steroid use to decrease the swallowed portion 1

Monitoring During Treatment

Track resolution of Cushingoid features systematically 1:

• Weight and body composition changes 1
• Blood pressure normalization 1
• Glucose levels 1
• Physical stigmata (facial plethora, striae, proximal muscle weakness, easy bruising) 1

Monitor for adrenal insufficiency during tapering 1:

• Fatigue and weakness 1
• Nausea and anorexia 1
• Hypotension 1
• Hypoglycemia 1

Common Pitfalls to Avoid

• Never abruptly stop glucocorticoids in patients on chronic therapy—this causes adrenal crisis 1
• Do not assume all Cushing syndrome is exogenous—always rule out endogenous causes before attributing symptoms solely to medication 2, 4
• Recognize that exogenous Cushing syndrome is the most common cause of Cushing syndrome overall, far exceeding endogenous etiologies 4, 5
• Be vigilant about occult sources including topical preparations on large body surface areas and compounded preparations 1