Is a standalone outpatient Corticotropin-Releasing Hormone (CRH) stimulation test necessary before Bilateral Inferior Petrosal Sinus Sampling (BIPSS) in patients with Adrenocorticotropic Hormone (ACTH)-dependent Cushing's syndrome?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: October 5, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Standalone Outpatient CRH Testing Before BIPSS in ACTH-Dependent Cushing's Syndrome

No, a standalone outpatient CRH stimulation test is not necessary before performing Bilateral Inferior Petrosal Sinus Sampling (BIPSS) in patients with ACTH-dependent Cushing's syndrome. 1, 2

Diagnostic Approach to ACTH-Dependent Cushing's Syndrome

  • ACTH-dependent Cushing's syndrome should first be confirmed by measuring ACTH levels, with levels >5 ng/L (>1.1 pmol/L) indicating ACTH dependency 1, 3
  • A cut-off value of 29 ng/L (6.4 pmol/L) for ACTH has 70% sensitivity and 100% specificity for diagnosing Cushing's disease 1, 3
  • After confirming ACTH dependency, pituitary MRI should be performed to identify a potential adenoma 2, 4

Role of BIPSS in Diagnosis

  • BIPSS is indicated when ACTH-dependent Cushing's syndrome is confirmed but no adenoma is identified on pituitary MRI 1, 2
  • BIPSS is considered the gold standard for differentiating between pituitary and ectopic sources of ACTH excess 2, 5
  • BIPSS should only be performed in specialized centers with experienced interventional radiologists 1

CRH Stimulation During BIPSS

  • CRH stimulation is administered during the BIPSS procedure itself, not as a separate outpatient test beforehand 1, 2
  • During BIPSS, a pituitary source of ACTH excess is confirmed by:
    • ≥2:1 ratio of central-to-peripheral ACTH before CRH stimulation 1, 2
    • ≥3:1 ratio of central-to-peripheral ACTH after CRH stimulation 1, 2
  • CRH stimulation during BIPSS significantly improves diagnostic accuracy compared to unstimulated sampling 2, 5

Important Procedural Considerations

  • Hypercortisolemia should be confirmed immediately prior to BIPSS to ensure the patient is in an active disease phase, especially important for cyclical Cushing's disease 1, 2
  • Medical therapy for Cushing's disease (steroidogenesis inhibitors) must be stopped before BIPSS to enable accurate interpretation of results 1
  • Either CRH or desmopressin can be used as stimulants during BIPSS with similar accuracy 1

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 stimulation 1
  • Lateralization accuracy varies, with studies showing 58-91% concordance with surgical findings 1, 2

Common Pitfalls to Avoid

  • Performing BIPSS without first confirming ACTH-dependent Cushing's syndrome biochemically 2, 4
  • Conducting BIPSS during a period of cyclic remission in patients with cyclical Cushing's disease 1, 2
  • Relying solely on BIPSS lateralization data for surgical planning, as false lateralization can occur due to altered pituitary blood flow 1, 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Diagnostic Approach to ACTH-Dependent Cushing's Syndrome

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Cushing's Syndrome Classification and Diagnosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Diagnostic Criteria for ACTH-Dependent Cushing's Syndrome

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.