Cushing's Syndrome
Cushing's syndrome results from prolonged exposure to excess cortisol, either from an endogenous source (pituitary adenoma causing Cushing's disease, adrenal tumor, or ectopic ACTH) or, more commonly, from exogenous corticosteroid medications. The excess cortisol drives a distinctive cluster of metabolic, cardiovascular, and musculoskeletal complications.
Symptoms
Progressive central weight gain with a relatively thin face and extremities, broad purple stretch marks (striae), easy bruising, muscle weakness especially in the proximal thighs, hypertension, high blood sugar, fatigue, depression, poor wound healing, and -- in women -- menstrual irregularity and hirsutism. A 'buffalo hump' fat pad at the posterior neck and a rounded 'moon face' are classic.
Causes and risk
Pituitary ACTH-secreting adenoma (Cushing's disease) causes 70% of endogenous cases. Adrenal adenoma or carcinoma, ectopic ACTH from a lung or pancreatic tumor account for the rest. Iatrogenic Cushing's from chronic steroid use is the most common overall cause.
How it is evaluated
Screening tests -- 24-hour urinary free cortisol, late-night salivary cortisol (two measurements), and 1 mg overnight dexamethasone suppression test -- establish hypercortisolism. ACTH level differentiates pituitary/ectopic (ACTH-dependent) from adrenal (ACTH-independent) causes. MRI of the pituitary and CT of the adrenal glands are the primary imaging modalities.
Treatment
Surgical resection is first-line for pituitary adenoma (transsphenoidal surgery) and adrenal tumors. Radiation therapy and medical management (ketoconazole, metyrapone, osilodrostat) are used when surgery fails or is not feasible. Ectopic ACTH requires treatment of the primary tumor. Gradual steroid taper manages iatrogenic Cushing's.