A specialised diagnostic procedure for ACTH-dependent Cushing syndrome

Inferior petrosal sinus sampling (IPSS), usually performed bilaterally, is a specialised catheter-based diagnostic test used in selected patients with confirmed ACTH-dependent Cushing syndrome. It helps determine whether excess adrenocorticotropic hormone (ACTH) is coming from the pituitary gland or from a source elsewhere in the body.

IPSS is not a screening test for Cushing syndrome and does not replace biochemical confirmation. It is generally considered after an endocrinologist has confirmed endogenous hypercortisolism and ACTH dependence, especially when pituitary MRI is negative, shows a small or uncertain lesion, or does not match the clinical and laboratory findings.

How does IPSS work?

The inferior petrosal sinuses are veins that drain blood from the pituitary region. During IPSS, thin catheters are guided through veins, usually from the groin, into the right and left inferior petrosal sinuses. Blood samples are collected simultaneously from both sides and from a peripheral vein. ACTH levels are compared before and after a stimulating agent is given according to protocol.

A central-to-peripheral ACTH gradient can support a pituitary source, while the absence of the expected gradient may suggest an ectopic source. Results must be interpreted by an experienced endocrine team together with the biochemical tests, imaging and the technical adequacy of catheter placement.

Who may be referred for IPSS?

• Patients with biochemically confirmed ACTH-dependent Cushing syndrome when the source remains uncertain.
• Patients with no visible pituitary lesion or an equivocal small lesion on MRI.
• Patients whose MRI findings do not adequately explain the hormonal test results.
• Selected patients being evaluated before pituitary surgery, after multidisciplinary endocrine review. Important: IPSS should be requested and interpreted within a coordinated endocrinology, pituitary surgery and interventional team. It should not be performed when hypercortisolism is unconfirmed or inactive because misleading results may occur.

Preparing for IPSS

• Review all endocrine test results and pituitary or body imaging with the treating team.
• Inform the team about anticoagulants, antiplatelet medicines, allergies, kidney disease and previous reactions to contrast.
• Complete requested blood tests, which may include blood count, kidney function and coagulation profile.
• Follow fasting and medication instructions exactly. Do not stop medicines unless the treating team advises it.
• Arrange for post-procedure observation and transport according to hospital instructions.

What happens after the procedure?

After catheter removal, pressure is applied to the access site and the patient is monitored for bleeding, pain, vital-sign changes and other complications. The laboratory measures ACTH in the paired samples, and the endocrinologist interprets the gradients in the context of the full clinical picture. The result guides the next diagnostic or surgical step rather than acting as a stand-alone diagnosis.

Benefits and risks

The main benefit of IPSS is improved localisation of ACTH production when non-invasive tests are inconclusive. This can help avoid inappropriate pituitary surgery or direct evaluation toward an ectopic ACTH source. As an invasive venous sampling procedure, it has risks such as access-site bleeding or bruising, contrast reaction, vein injury, blood clot formation and, rarely, neurological complications. The team explains the individual benefit-risk balance before the test.