A 40-year-old man presents with features suggesting Cushing's syndrome. Which test is most appropriate to diagnose this condition?

• A. 24-hour urinary free cortisol
• B. ACTH stimulation test
• C. Serum cortisol after waking
• D. Overnight dexamethasone suppression test

Answer: (D)

The test relies on whether the body's cortisol production can be suppressed by a small amount of dexamethasone given overnight. In healthy individuals, dexamethasone lowers ACTH and hence cortisol levels by negative feedback, so the next morning a low cortisol is expected. In Cushing's syndrome, cortisol remains inappropriately high because cortisol production is autonomous and not suppressed by dexamethasone. This makes the overnight dexamethasone suppression test a practical and reliable screen for hypercortisolism.

Why this test fits best here: it’s quick and convenient, typically requiring a single overnight dose and a morning blood sample, with good overall specificity for detecting cortisol excess. In contrast, measuring 24-hour urinary free cortisol, while useful, requires accurate urine collection and can be influenced by various factors; a single morning serum cortisol lacks reliability due to natural diurnal variation; and an ACTH stimulation test is used after hypercortisolism is suspected to differentiate etiologies, not to screen for it.