Screening test: 24‑hour urinary free cortisol – reveals elevated cortisol. Low‑dose (overnight) dexamethasone suppression test – used to establish diagnosis of Cushing's syndrome. Give 1 mg dexamethasone at midnight. Measure serum cortisol at 8–9 am. If cortisol <50 nmol/L, Cushing's is unlikely. ACTH level – differentiates ACTH‑dependent vs ACTH‑independent causes. ACTH‑dependent (↑ ACTH) ACTH‑independent (↓ ACTH) Cushing's disease (pituitary adenoma) Adrenal adenoma Ectopic ACTH secretion (e.g., small cell lung cancer, carcinoid tumour) Adrenal carcinoma Exogenous glucocorticoid administration High‑dose dexamethasone suppression test – differentiates pituitary vs ectopic source of ACTH. Give 8 mg dexamethasone at midnight. Measure serum cortisol at 8–9 am. Pituitary adenoma → cortisol suppressed (↓ ACTH, ↓ cortisol). Ectopic source → cortisol NOT suppressed (↑ ACTH, ↑ cortisol). Treatment (by cause) : Iatrogenic: stop medication if possible. Cushing's disease (pituitary adenoma) : surgical removal of pituitary adenoma. Adrenal adenoma or carcinoma: adrenalectomy. Ectopic ACTH: surgery (if cancer not yet spread). Drugs that reduce cortisol secretion: metyrapone, ketoconazole, fluconazole.
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