Pitfalls in Performing and Interpreting Inferior Petrosal Sinus Sampling: Personal Experience and Literature Review

J Clin Endocrinol Metab. 2021 Apr 23;106(5):e1953-e1967. doi: 10.1210/clinem/dgab012.


Context: Inferior petrosal sinus sampling (IPSS) helps differentiate the source of ACTH-dependent hypercortisolism in patients with inconclusive biochemical testing and imaging, and is considered the gold standard for distinguishing Cushing disease (CD) from ectopic ACTH syndrome. We present a comprehensive approach to interpreting IPSS results by examining several real cases.

Evidence acquisition: We performed a comprehensive review of the IPSS literature using PubMed since IPSS was first described in 1977.

Evidence synthesis: IPSS cannot be used to confirm the diagnosis of ACTH-dependent Cushing syndrome (CS). It is essential to establish ACTH-dependent hypercortisolism before the procedure. IPSS must be performed by an experienced interventional or neuroradiologist because successful sinus cannulation relies on operator experience. In patients with suspected cyclical CS, it is important to demonstrate the presence of hypercortisolism before IPSS. Concurrent measurement of IPS prolactin levels is useful to confirm adequate IPS venous efflux. This is essential in patients who lack an IPS-to-peripheral (IPS:P) ACTH gradient, suggesting an ectopic source. The prolactin-adjusted IPS:P ACTH ratio can improve differentiation between CD and ectopic ACTH syndrome when there is a lack of proper IPS venous efflux. In patients who have unilateral successful IPS cannulation, a contralateral source cannot be excluded. The value of the intersinus ACTH ratio to predict tumor lateralization may be improved using a prolactin-adjusted ACTH ratio, but this requires further evaluation.

Conclusion: A stepwise approach in performing and interpreting IPSS will provide clinicians with the best information from this important but delicate procedure.

Keywords: IPSS; case-based review; interpretation; performance.

Publication types

  • Review

MeSH terms

  • ACTH Syndrome, Ectopic / diagnosis*
  • Diagnosis, Differential
  • Humans
  • Petrosal Sinus Sampling / methods*
  • Petrosal Sinus Sampling / standards*
  • Pituitary ACTH Hypersecretion / diagnosis*