Diagnostic Criteria for ACTH-Dependent Cushing's Syndrome

Diagnostic Tests

The Endocrine Society recommends confirming hypercortisolism using at least two first-line tests, including late-night salivary cortisol (LNSC), 24-hour urinary free cortisol (UFC), and low-dose dexamethasone suppression test (LDDST), with sensitivity and specificity of 95% and 100% for LNSC, 89% and 100% for UFC, and 95% and 80% for LDDST 1, 2
The overnight dexamethasone suppression test has a diagnostic cut-off of ≥50 nmol/L (≥1.8 μg/dL) and sensitivity of 95% 1, 4, 5
The serum cortisol circadian rhythm study has a midnight diagnostic cut-off of ≥50 nmol/L (≥1.8 μg/dL) and sensitivity of 100% 1, 3, 5

Morning plasma ACTH levels >5 ng/L or >1.1 pmol/L indicate ACTH-dependent Cushing's, with a cut-off value of 29 ng/L (6.4 pmol/L) having sensitivity of 70% and specificity of 100% 1, 2, 4
The CRH stimulation test has a ≥20% increase in cortisol from baseline to support pituitary origin, with sensitivity of 74-100% 1, 4, 6
Pituitary MRI has adenoma detection sensitivity of 63% and specificity of 92% 1, 3
Bilateral inferior petrosal sinus sampling (BSIPSS) has diagnostic criteria of central-to-peripheral ACTH ratio ≥2:1 before stimulation and ≥3:1 after stimulation, with sensitivity of 100% 2, 3, 4

The American Academy of Pediatrics recommends screening for Cushing's syndrome in patients with unexplained weight gain combined with either decreased height SDS or height velocity 5
The Endocrine Society suggests ruling out exogenous glucocorticoid use before biochemical testing and confirming hypercortisolemia immediately prior to BSIPSS to ensure active disease phase 2, 3, 4, 5