Inferior petrosal sinus sampling in the differential diagnosis of ACTHD-dependent Cushing's syndrome

The diagnostic differentiation between Cushing's disease and ectopic adrenocorticotropic hormone (ACTH) syndrome is frequently difficult, because dynamic biochemical testing and/or radiological imaging are commonly inconclusive. Direct inferior petrosal sinus sampling (IPSS) for ACTH is considered by many to be the most accurate test for this differential diagnosis. IPSS involves simultaneous blood sampling for ACTH from the right inferior petrosal sinus (IPS), left IPS, and a peripheral vein both before and after corticotropin-releasing hormone (CRH) stimulation. A basal central to peripheral ratio (C:P ratio) greater than or equal to2 or a stimulated C:P ratio greater than or equal to3 suggests Cushing's disease, whereas ratios <2 and <3, respectively, suggest ectopic ACTH syndrome. In experienced centers, the diagnostic sensitivity and specificity of IPSS approaches 100%. The indications for IPSS are debated, with some advocating use when standard dynamic tests are inconclusive, and others advocating use only when pituitary magnetic resonance imaging (MRI) is inconclusive. Intersinus ACTH gradients greater than or equal to1.4 may suggest a lateralization of ACTH secreting pituitary tumors, but the utility of IPSS in this situation is less clear. In experienced hands, IPSS is generally safe, but serious complications may rarely occur. Although some advocate direct sampling from the cavernous sinuses, this method does not seem to be superior to IPSS.