Jugular Vein Sampling for Hormone Levels for the Diagnosis of Cushing Syndrome

Sampling from the inferior petrosal sinuses for ACTH levels differentiates Cushing disease from the ectopic ACTH syndrome in nearly all patients. Patients with corticotroph tumors have a petrosal-to-peripheral ACTH gradient of 2 or more, while patients with other causes of Cushing syndrome have lower gradients. Bilateral petrosal sinus sampling also often provides useful information on lateralization of the adenoma for the neurosurgeon. The widespread application of inferior petrosal sinus sampling has been limited by concerns about potential complications and by technical failures in the hands of less experienced radiologists. In this protocol, we compare ACTH levels in the internal jugular veins before and after CRH stimulation with those obtained by conventional inferior petrosal sinus sampling from patients with Cushing's syndrome. Obtaining blood from the jugular veins is a simple, practically risk-free procedure that could be accomplished easily in community hospitals on an outpatient basis. We hypothesize that corticotropin-releasing hormone (CRH) stimulation will increase ACTH production from corticotroph adenomas so that the diagnostic information from jugular venous sampling would be equivalent to that obtained by catheterization of the petrosal sinuses. Currently fewer than ten centers in the United States have sufficient technical expertise with inferior petrosal sinus sampling (IPSS) to ensure reliable results. This proposal to develop jugular venous sampling (JVS) with CRH stimulation as a test for the differential diagnosis of Cushing syndrome would potentially contribute greatly to the medical care of patients with Cushing syndrome, as a less costly, safer and more widely available alternative to inferior petrosal sinus sampling. Initial data from 35 patients undergoing both JVS and IPSS revealed no technical problems with either procedure. IPSS correctly identified 28/31 patients with Cushing disease, while JVS correctly identified 23 of these patients using conventional criteria (petrosal:peripheral greater than 2 before or 3 after CRH administration). Thus, JVS may be a useful initial procedure at institutions where IPSS is not available. However, since it is likely that jugular:peripheral ratios will be lower in patients with ectopic ACTH secretion (so far, 1.2 - 2.04), the protocol evaluates also the performance of JVS in patients with ectopic ACTH secretion to determine whether the criteria for interpretation of JVS should be different than those used for IPSS.