A 38-year-old woman presents with weight gain, proximal myopathy, and hypertension. Overnight 1 mg dexamethasone suppression test shows cortisol of 6.8 mcg/dL (normal <1.8). Late-night salivary cortisol is elevated on two occasions. ACTH level is 85 pg/mL (normal 10–60). MRI pituitary shows a 5 mm hypointense lesion. Which additional test most reliably confirms pituitary Cushing's disease vs ectopic ACTH?

• A High-dose (8 mg) dexamethasone suppression test
• B Urine free cortisol on 24-hour collection
• C CT chest and abdomen for ectopic source
• D Inferior petrosal sinus sampling (IPSS) with CRH stimulation ✓

Explanation

IPSS with CRH stimulation is the gold standard for differentiating pituitary from ectopic ACTH secretion; a central-to-peripheral ACTH gradient >2 basal or >3 post-CRH confirms pituitary origin. High-dose dexamethasone suppression has lower specificity (~80%) and can give false positives. 24-hour urine free cortisol confirms hypercortisolism but does not lateralise the source. CT imaging identifies tumours but cannot confirm biochemical source.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.