Inferior Petrosal Sinus Sampling Protocol for ACTH-Dependent Cushing Syndrome
Pre-Procedure Requirements
BIPSS should only be performed after confirming active hypercortisolism on the morning of the procedure, particularly critical in patients with cyclical disease. 1, 2
Mandatory Pre-Procedure Checklist:
Confirm ACTH-dependent Cushing syndrome biochemically before scheduling BIPSS—the procedure cannot diagnose Cushing syndrome itself, only localize the ACTH source 1, 3
Discontinue all steroidogenesis inhibitors (ketoconazole, metyrapone, etc.) with appropriate washout periods based on each drug's half-life 1, 2, 4
Document active hypercortisolism on the same morning using late-night salivary cortisol, 24-hour urinary free cortisol, or dexamethasone suppression test to ensure patients with cyclic disease are in an active phase 1, 2, 4
Perform the procedure only in specialized centers with experienced interventional radiologists, as diagnostic accuracy and complication rates are highly operator-dependent 1, 2, 4
Sampling Protocol
Catheter Placement:
Bilateral catheterization of both inferior petrosal sinuses is mandatory—successful bilateral cannulation should exceed 85% in experienced hands 1
Simultaneous peripheral venous sampling (typically femoral vein) is required for ratio calculations 3, 5
Measure prolactin levels from both petrosal sinuses to confirm adequate venous efflux and proper catheter positioning 1, 3, 6, 7
Sampling Timepoints:
Baseline samples: Draw ACTH and prolactin from both inferior petrosal sinuses and peripheral vein before any stimulation 1, 4, 3
Administer CRH or desmopressin (DDAVP) for stimulation—both are acceptable, though CRH is necessary for optimal diagnostic accuracy 1, 4
Post-stimulation samples: Draw ACTH and prolactin at 3,5, and 10 minutes after CRH administration (or appropriate intervals for desmopressin) 1, 4
Diagnostic Interpretation Criteria
Standard ACTH Ratios:
A central-to-peripheral ACTH ratio ≥2:1 at baseline OR ≥3:1 after CRH/desmopressin stimulation confirms a pituitary source with 96-100% sensitivity and near-100% specificity. 1, 2, 4
Prolactin-Adjusted Interpretation:
Calculate IPS:peripheral prolactin ratios to verify adequate pituitary venous drainage—a dominant basal IPS:peripheral prolactin ratio >1.8 confirms proper sampling 7
When baseline IPS:peripheral prolactin is <1.2, suspect inadequate pituitary venous efflux and apply prolactin-normalized ACTH ratios 7
Prolactin-normalized ACTH IPS:peripheral ratio ≥0.8 (or ≥0.33 using optimized cutoffs) supports pituitary Cushing disease when standard ratios are equivocal 6, 7
This prolactin adjustment is essential in patients lacking an IPS:peripheral ACTH gradient who would otherwise be misclassified as ectopic ACTH syndrome 3, 7
Lateralization (Optional):
An inter-petrosal sinus ACTH gradient ≥1.4 after stimulation suggests tumor lateralization, though concordance with surgical findings ranges only 58-87.5% 1, 2, 4
Prolactin-adjusted inter-sinus ACTH ratios may improve lateralization accuracy but require further validation 3
Critical Pitfalls to Avoid
Never use BIPSS as a first-line test—reserve it for cases where pituitary MRI shows no adenoma or lesions <6 mm 1, 4
Do not proceed if only unilateral IPS cannulation is achieved—a contralateral pituitary source cannot be excluded with single-sided sampling 3
Always measure prolactin concurrently—failure to do so may result in false-negative results (1-10% false-negative rate) when venous drainage is suboptimal 3, 7
Recognize that internal jugular vein sampling is NOT an acceptable alternative—sensitivity is only 68.7% compared to 93.8% for IPSS 5