What is the management of Cushing's syndrome caused by exogenous (external) steroids, specifically corticosteroids (e.g. prednisone)?

Management of Cushing's Syndrome Due to Exogenous Steroids

The primary management of exogenous Cushing's syndrome is to stop or gradually taper the causative glucocorticoid if clinically feasible, as this is the most direct and effective intervention. 1

Initial Assessment and Diagnosis

When Cushing's syndrome is suspected, the first critical step is determining whether the patient is taking exogenous glucocorticoids in any form 1:

• Identify all sources of exogenous steroids: oral medications (prednisone, prednisolone, methylprednisolone), inhaled corticosteroids, topical preparations (including clobetasol propionate), intra-articular injections, and intranasal formulations 1, 2
• Screen for drug interactions: Combination of itraconazole with methylprednisolone or inhaled budesonide/fluticasone significantly increases risk of exogenous Cushing's syndrome and adrenal insufficiency 1
• Assess duration and cumulative dose: Long-term use of >7.5 mg prednisone daily inevitably causes iatrogenic Cushing's syndrome 3

Management Strategy

Discontinuation or Tapering Protocol

Abrupt withdrawal must be avoided due to risk of life-threatening adrenal insufficiency from hypothalamic-pituitary-adrenal (HPA) axis suppression 4, 5:

• Gradual dose reduction in small increments at appropriate time intervals until the lowest effective dose is reached 4
• Taper rate depends on: duration of therapy, total cumulative dose, individual patient factors, and underlying disease activity 4, 5
• HPA axis suppression can persist for up to 12 months after discontinuation, requiring stress-dose coverage during intercurrent illness or surgery 4

Monitoring During Taper

Reduce maintenance dosing if symptoms of iatrogenic Cushing's syndrome develop, including 1:

• Bruising and thin skin
• Edema and weight gain
• Hypertension
• Hyperglycemia

Distinguish between three overlapping syndromes during the taper 5:

• Active Cushing's syndrome from ongoing steroid exposure
• Glucocorticoid withdrawal syndrome (fatigue, myalgias, arthralgias)
• Adrenal insufficiency from HPA axis suppression

Assessment of Adrenal Recovery

Do not completely stop glucocorticoid therapy until recovery of adrenal function is confirmed 5:

• Morning cortisol levels: If <3 mcg/dL, indicates adrenal insufficiency; if >15 mcg/dL, suggests recovery 1
• ACTH stimulation testing: Consider for indeterminate morning cortisol results (3-15 mcg/dL) 1
• Recovery time is variable: Depends on dose and duration of prior treatment 4

Management of Complications

Adrenal Insufficiency During Taper

If adrenal insufficiency develops 1:

Grade 1-2 (Mild to Moderate):

• Initiate hydrocortisone 15-20 mg daily in divided doses (two-thirds morning, one-third early afternoon) 1
• Titrate to maximum 30 mg daily for residual symptoms 1
• Endocrinology consultation 1

Grade 3-4 (Severe/Life-threatening):

• Hospitalize immediately 1
• IV hydrocortisone 50-100 mg every 6-8 hours 1
• Normal saline (at least 2L) 1
• Taper stress-dose corticosteroids to oral maintenance over 5-7 days 1

Stress Dosing Education

All patients on chronic glucocorticoids or recovering from HPA suppression require 1, 4:

• Education on stress dosing for illness, surgery, or trauma
• Emergency injectable glucocorticoid supply
• Medical alert bracelet or identification system
• Instructions on when to seek emergency care

Specific Considerations for Different Formulations

Topical steroids: Clobetasol propionate doses exceeding 50 g/week should not be prescribed; avoid occlusive dressings 2

Inhaled corticosteroids: When combined with azole antifungals (itraconazole), can cause exogenous Cushing's syndrome; monitor closely 1

Long-acting vs. short-acting steroids: Hydrocortisone allows recreation of diurnal cortisol rhythm (preferred); prednisone carries higher risk of over-replacement but may be used if adherence to short-acting regimen is problematic (hydrocortisone 20 mg = prednisone 5 mg) 1

Common Pitfalls to Avoid

• Never stop steroids abruptly in patients on chronic therapy—this can precipitate adrenal crisis 4
• Do not overlook non-oral routes of glucocorticoid administration (topical, inhaled, intra-articular) as causes of iatrogenic Cushing's 1, 2, 6
• Avoid over-replacement during taper—monitor for signs of iatrogenic Cushing's and adjust accordingly 1
• Screen for drug interactions particularly with azole antifungals that potentiate glucocorticoid effects 1
• Ensure stress-dose coverage during intercurrent illness or procedures even after apparent recovery, as HPA suppression may persist 4