Overview
Definition
A clinical syndrome resulting from chronic, excessive exposure to glucocorticoids (cortisol).
Epidemiology
Iatrogenic (exogenous) is the most common cause overall. Endogenous causes are rare and more common in women.
Etiology & Risk Factors
- Exogenous: Prolonged use of exogenous corticosteroids (e.g., Prednisone)
- Cushing's Disease (70% of endogenous): ACTH-secreting pituitary adenoma
- Ectopic ACTH secretion (15%): Usually from Small Cell Lung Cancer
- Adrenal adenoma/carcinoma (15%): Cortisol-secreting tumor independent of ACTH
Clinical Symptoms
- Central obesity with thin extremities
- 'Moon facies' (round face) and 'Buffalo hump' (dorsocervical fat pad)
- Purple abdominal striae (stretch marks)
- Proximal muscle weakness
- Hirsutism and acne (in women)
- Hypertension and hyperglycemia
Clinical Approach
Diagnosis
- Initial Screening (need 2 abnormal tests): 24-hour urine free cortisol, Late-night salivary cortisol, Low-dose Dexamethasone suppression test (cortisol remains high)
- Determining the Source: Check ACTH level. If ACTH is high, it's ACTH-dependent (Pituitary vs Ectopic). If ACTH is low, it's ACTH-independent (Adrenal).
- High-dose Dexamethasone suppression test: Suppresses pituitary Cushing's, but NOT ectopic Cushing's.
Management
- Exogenous: Gradually taper steroids if possible
- Pituitary Adenoma: Transsphenoidal surgical resection
- Adrenal/Ectopic tumors: Surgical resection
- Medical block: Ketoconazole, Metyrapone (inhibits steroidogenesis)
Complications
- Osteoporosis and fractures
- Severe infections (immunosuppression)
- Diabetes mellitus
- Cardiovascular disease