Inferior petrosal sinus sampling in Cushing's syndrome: usefulness and pitfalls

In patients with ACTH-dependent Cushing's syndrome (CS), the differentiation between Cushing's disease (CD) and ectopic ACTH secretion (EAS) can often be challenging. The traditionally used biochemical tests have limited diagnostic accuracy and imaging modalities may fail to detect the culprit lesion. Inferior petrosal sinus sampling (IPSS) was introduced more than 3 decades ago as a test with optimal diagnostic accuracy and has since become the gold standard in the differential diagnosis between CD and EAS. However, several, albeit rare, pitfalls may limit its diagnostic accuracy and awareness is needed to avoid incorrect interventions. Moreover, it is an invasive and demanding procedure, available in a limited number of centers worldwide. This review aims to critically present the usefulness and pitfalls of IPSS and define strategies for its optimal place in the contemporary management of CS.