Will Bilateral Inferior Petrosal Sinus Sampling (BIPSS) differentiate between ectopic and pituitary sources of Adrenocorticotropic Hormone (ACTH)-dependent Cushing's syndrome and is a Corticotropin-Releasing Hormone (CRH) stimulation test needed?

Bilateral Inferior Petrosal Sinus Sampling (BIPSS) for Differentiating Ectopic from Pituitary ACTH Sources

Yes, BIPSS effectively differentiates between ectopic and pituitary sources of ACTH-dependent Cushing's syndrome, and CRH stimulation is necessary for optimal diagnostic accuracy. 1

BIPSS Diagnostic Value

• BIPSS has high sensitivity for distinguishing between pituitary (Cushing's disease) and ectopic sources of ACTH, with a sensitivity of 88-100% and specificity of 67-100% 2
• BIPSS should be offered to patients with confirmed ACTH-dependent Cushing's syndrome when no adenoma is identified on pituitary MRI 1
• The procedure must be performed at a specialized center by an experienced interventional radiologist who regularly performs this procedure 1

CRH Stimulation Requirement

• CRH stimulation is essential during BIPSS to enhance the sensitivity of the procedure 3, 2
• A pituitary source of ACTH excess is confirmed by:
  • ≥2:1 ratio of central-to-peripheral ACTH before CRH stimulation 1
  • ≥3:1 ratio of central-to-peripheral ACTH after CRH stimulation 1
• Either CRH or desmopressin can be used as stimulants, with similar accuracy reported in pediatric series 1

Procedural Considerations

• Hypercortisolemia must be confirmed immediately prior to BIPSS to ensure the patient is in an active disease phase, especially important for cyclical Cushing's disease 1
• Medical therapy for Cushing's disease (steroidogenesis inhibitors) must be discontinued before BIPSS to enable accurate interpretation of results 1
• The procedure should only be performed after ACTH-dependent Cushing's syndrome has been biochemically confirmed 4

Additional Benefits of BIPSS

• BIPSS may help lateralize the pituitary adenoma when no lesion is visible on MRI 1
• Lateralization is suggested by an inter-petrosal sinus ACTH gradient ≥1.4 between the two sides after CRH or desmopressin stimulation 1
• Lateralization accuracy varies, with studies showing 58-91% concordance with surgical findings 1

Important Caveats

• BIPSS should not be used as a first-line test but reserved for cases where MRI does not show a clear pituitary adenoma 1, 4
• Despite its value for lateralization, BIPSS has limited accuracy (50-70% positive predictive value) for precise tumor localization within the pituitary 2
• False lateralization can occur due to altered pituitary blood flow, though this appears less problematic than previously thought 1
• Accurate catheterization is crucial; prolactin measurements during BIPSS have been used as markers of proper catheter placement, though their value for improving lateralization accuracy remains debated 1

In conclusion, for your upcoming MRI, if no clear pituitary adenoma is identified, BIPSS with CRH stimulation will be the next critical step to definitively differentiate between pituitary and ectopic sources of ACTH excess, which is essential for determining the appropriate surgical approach and optimizing outcomes 1, 5.