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Consensus Guidelines on Inferior Petrosal Sinus Sampling: A Guideline From the Society of Vascular and Interventional
Farhan Siddiq1, Hunter Brooks1, Esra Demirtas2
1Department of Neurosurgery (F.S., H.B., I.A.B.), University of Missouri, Columbia.
Background:
Bilateral inferior petrosal sinus sampling (BIPSS) is the gold-standard test to distinguish Cushing disease (CD) from ectopic adrenocorticotropic hormone (ACTH) secretion when biochemistry confirms ACTH-dependent Cushing syndrome and pituitary magnetic resonance imaging is equivocal. However, practice varies widely between centers, leading to false negatives, misinterpretation, sampling errors, and avoidable risk. Neurointerventionalists performing BIPSS have lacked dedicated, procedure-focused guidance.
Methods:
Using the Society of Vascular and Interventional Neurology Guidelines and Practice Standards framework, a multidisciplinary panel (endocrinology, interventional neuroradiology, and endovascular neurosurgery) performed a systematic review through August 2025 and developed recommendations graded by class of recommendation and level of evidence through a modified Delphi process.
Results:
The guideline standardizes (1) indications for BIPSS in biochemically confirmed ACTH-dependent Cushing with normal, equivocal, or <6 mm pituitary lesions; (2) technical approach, including bilateral IPS catheterization, heparinization, and stimulation with corticotropin-releasing hormone or desmopressin; (3) sampling protocol with 2 prestimulation draws and timed collections at 3, 5, 10, and 15 minutes; (4) lab handling, emphasizing prechilled EDTA tubes, rapid ACTH processing, and prolactin measurement as an internal control of venous effluent; and (5) interpretation, using ACTH inferior petrosal sinus to peripheral ratio cutoffs (≥2 prestimulation, ≥3 poststimulation) and techniques to identify potential false negatives. The document also defines operator/institutional competency benchmarks and quality-assurance metrics.
Conclusions:
When executed with standardized technique and interpretation, BIPSS offers very high sensitivity and specificity for localizing ACTH pathology. These consensus guidelines provide a practical playbook for neurointerventionalists to perform BIPSS safely, reproducibly, and with maximal diagnostic yield.
