Diagnosing Hypercortisolism

Confirming Hypercortisolism

• The Endocrine Society recommends confirming hypercortisolism using one of the first-line tests, including 24-hour urinary free cortisol, late-night salivary cortisol, or 1 mg overnight dexamethasone suppression test, with a normal suppression being cortisol <1.8 μg/dL 1

Differentiating ACTH-Dependent from ACTH-Independent Disease

• The American College of Endocrinology suggests measuring morning plasma ACTH to distinguish ACTH-dependent from ACTH-independent disease, with ACTH >5 ng/L indicating ACTH-dependent disease with high certainty 2
• ACTH >29 ng/L has 70% sensitivity and 100% specificity for Cushing's disease specifically 2

Localizing the Source of ACTH-Dependent Disease

• High-quality pituitary MRI (3T preferred over 1.5T) with thin slices should be performed to detect pituitary adenomas, and if an adenoma ≥10 mm is detected, BIPSS is not necessary for diagnosis 1, 2
• If no adenoma or lesion <6 mm is detected, proceed to BIPSS 1, 2

Diagnostic Criteria for BIPSS

• Central-to-peripheral ACTH ratio ≥2:1 before stimulation suggests pituitary source, and central-to-peripheral ACTH ratio ≥3:1 after CRH or desmopressin stimulation confirms pituitary source 1
• Ratio <2 before or <3 after stimulation suggests ectopic tumor 1

Advanced Imaging for Ectopic ACTH Syndrome

• 68Ga-DOTATATE PET imaging is useful for localizing ectopic ACTH-secreting neuroendocrine tumors, with a sensitivity of approximately 65% 1