What is Inferior Petrosal Sinus Sampling (IPSS)?

Inferior Petrosal Sinus Sampling (IPSS)

Inferior Petrosal Sinus Sampling (IPSS) is a specialized diagnostic procedure that measures ACTH gradients between the pituitary venous drainage and peripheral circulation to differentiate between pituitary and non-pituitary sources of ACTH-dependent Cushing's syndrome when MRI findings are inconclusive.

Purpose and Indications

• IPSS is considered the gold standard for distinguishing Cushing disease (pituitary source) from ectopic ACTH syndrome 1
• Primary indication: Patients with confirmed ACTH-dependent Cushing syndrome and no identified adenoma on pituitary MRI 2
• IPSS should only be performed after biochemical confirmation of ACTH-dependent hypercortisolism 1

Procedure Details

• Bilateral sampling of the inferior petrosal sinuses (which drain the pituitary gland) is performed by an experienced interventional radiologist 2
• Blood samples are collected simultaneously from both petrosal sinuses and a peripheral vein
• Samples are taken at baseline and after stimulation with either:
  • Corticotropin-releasing hormone (CRH) 2
  • Desmopressin (DDAVP) as an alternative stimulant 2

Diagnostic Criteria

• A pituitary source of ACTH excess is confirmed by:
  • ≥2:1 ratio of central-to-peripheral ACTH before stimulation 2
  • ≥3:1 ratio of central-to-peripheral ACTH after stimulation 2
• These criteria have high sensitivity for Cushing disease in experienced centers 2

Tumor Lateralization

• IPSS can help lateralize the pituitary tumor when no lesion is visible on MRI 2
• An inter-petrosal sinus ACTH gradient ≥1.4 after stimulation may indicate tumor lateralization 2
• Lateralization accuracy varies:
  • Some studies report 87-91% concordance with surgical findings 2
  • Other studies show lower accuracy (58-70%) 2
  • More recent data (2021-2022) confirm similar or higher (87.5%) accuracy 2

Technical Considerations

• Hypercortisolemia should be confirmed immediately before IPSS to ensure active disease, especially in cyclical Cushing's disease 2
• Medical therapy for Cushing disease must be stopped before IPSS 2
• Prolactin measurement during IPSS can serve as a marker of accurate catheterization 2, 3
• Prolactin-adjusted ACTH ratios may improve diagnostic accuracy when there is inadequate venous sampling 1

Limitations and Pitfalls

• False lateralization can occur due to altered pituitary blood flow 2
• Procedure reliability depends on the experience of the radiology team 2
• Technical difficulties or anatomical variants may prevent successful bilateral cannulation 4
• IPSS cannot be used to confirm the diagnosis of ACTH-dependent Cushing syndrome itself 1

Clinical Implementation

• IPSS should only be performed in specialized centers with expertise in this procedure 2
• In adult practice, IPSS is routine unless MRI unequivocally shows a pituitary adenoma that is unlikely to be an incidentaloma 2
• When IPSS results predict an ectopic source but none can be found, exploratory transsphenoidal surgery should be considered, as studies show 95% of such cases have a surgically proven pituitary source 4

Outcomes Impact

• Observational studies suggest that the introduction of IPSS may improve rates of surgical cure in patients with Cushing's disease 2
• Selective adenomectomy is the first-line treatment for Cushing's disease, with IPSS helping to guide the surgical approach when MRI is negative 2

IPSS is a valuable but technically demanding procedure that requires proper patient selection, experienced operators, and careful interpretation of results to maximize its diagnostic utility in the management of ACTH-dependent Cushing's syndrome.