Iatrogenic Cushingoid Features
Iatrogenic Cushingoid features are the physical manifestations of Cushing syndrome caused by exogenous glucocorticoid administration through any route—oral, topical, inhaled, or ocular—and include moon facies, buffalo hump, purple striae, truncal obesity, proximal muscle weakness, easy bruising, and supraclavicular fat accumulation. 1
Physical Examination Findings
The characteristic physical features that develop from exogenous glucocorticoid exposure include: 1
- Moon facies (rounded, full facial appearance) 1, 2
- Buffalo hump (dorsocervical fat pad accumulation) 1
- Purple striae (wide, violaceous stretch marks on abdomen, thighs, or breasts) 1
- Truncal obesity with centripetal fat distribution 1
- Supraclavicular fullness (fat accumulation above the clavicles) 3
- Proximal muscle weakness (difficulty rising from a chair or climbing stairs) 1
- Easy bruising and skin fragility 1
- Facial plethora (reddish facial appearance) 4
- Acne 1
- Increased lanugo hair or hirsutism 1, 3
Metabolic and Systemic Manifestations
Beyond physical appearance, iatrogenic Cushing syndrome causes significant metabolic derangements: 2, 5
- Hypertension (present in >80% of cases) 1, 5
- Hyperglycemia and glucose intolerance (present in >80% of cases) 5, 4
- Metabolic alkalosis with hypokalemia 1
- Weight gain (though paradoxically, weight loss can occur in 10% of cases associated with malignancy) 1, 4
- Peripheral edema 1
Behavioral and Growth Effects
Particularly important in pediatric populations: 1, 6
- Growth deceleration and stunted growth 1, 6
- Irritability, fussiness, and personality changes (up to 29% of patients) 1
- Insomnia 1
- Mood disorders including depression and anxiety 5, 4
Critical Diagnostic Consideration
Before pursuing any biochemical testing for Cushing syndrome, exogenous glucocorticoid use must be excluded through detailed medication history. 1 The Endocrine Society emphasizes this as a strong recommendation based on high-quality evidence, as failure to exclude iatrogenic causes leads to unnecessary testing and potential harm without patient benefit. 1
Routes of Exposure to Assess
Iatrogenic Cushing syndrome can result from: 1, 6, 7, 8
- Oral glucocorticoids (most common) 4, 7
- Topical ocular corticosteroids (even at low doses, particularly in children) 6, 8, 3
- High-potency topical skin corticosteroids 1
- Inhaled corticosteroids (especially when combined with itraconazole) 1
- Intralesional corticosteroid injections 1
- Over-the-counter supplements containing undisclosed steroids 7
Common Pitfall: Drug Interactions
The combination of methylprednisolone with oral itraconazole, or inhaled budesonide/fluticasone with itraconazole, significantly increases the risk of exogenous Cushing syndrome and adrenal insufficiency due to CYP3A4 inhibition. 1 This interaction potentiates glucocorticoid effects and must be avoided or carefully monitored.
Life-Threatening Complication: HPA Axis Suppression
Chronic exogenous glucocorticoid exposure (particularly ≥2 years) causes complete suppression of the hypothalamic-pituitary-adrenal axis with adrenal atrophy, creating extreme risk of life-threatening adrenal crisis if steroids are abruptly discontinued. 2, 8, 3 Laboratory confirmation shows undetectable ACTH and cortisol levels. 2, 6, 8, 3
Abrupt withdrawal has precipitated documented adrenal crises requiring emergency management. 3 Any tapering must be gradual over 3-6 months with stress-dose protocols during physiologic stress. 2
Rare but Documented: Minimal Exposure Cases
Even extremely low doses of topical ocular steroids can cause iatrogenic Cushing syndrome, particularly in children or those with genetic variations in the glucocorticoid receptor gene (NR3C1). 6, 8 Cases have been documented with dexamethasone 2% eye drops used for as little as 6 months. 6, 8, 3