Which of the following is the most sensitive biochemical screening test for Cushing's syndrome?
- A 8 AM serum cortisol
- B Plasma ACTH
- C Late-night salivary cortisol (two measurements) ✓
- D CRH stimulation test
Correct answer: C. Late-night salivary cortisol (two measurements)
Explanation
Late-night salivary cortisol has sensitivity and specificity exceeding 90% for Cushing's syndrome and reflects the loss of normal diurnal cortisol nadir at midnight. The Endocrine Society recommends three first-line tests: late-night salivary cortisol, 24-hour urinary free cortisol, or 1 mg overnight dexamethasone suppression test. Plasma ACTH differentiates ACTH-dependent from ACTH-independent disease after diagnosis, not for screening. 8 AM serum cortisol alone is not a reliable screening test.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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