Bilateral sequential inferior petrosal sinus sampling with corticotrophin-releasing hormone stimulation in the diagnosis of Cushing’s disease S J Padayatty 1,3 , S M Orme 1 , M Nelson 1,2 , J T Lamb 2 and P E Belchetz 1 1 Department of Endocrinology and 2 Department of Neuroradiology, The General Infirmary at Leeds, Leeds LS13EX, UK and 3 Division of Endocrinology, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA (Correspondence should be addressed to S J Padayatty, Payson House #14C, 435 East 70 th Street, Manhattan, New York, New York 10021 USA) Abstract Objective: The demonstration of a central to peripheral ACTH gradient in a hypercortisolaemic patient is diagnostic of Cushing’s disease. We tried to determine whether single blood samples for ACTH obtained sequentially from each of the inferior petrosal sinuses following human corticotrophin-releasing hormone (hCRH) stimulation can reliably establish such a gradient. Design: Prospective study. Patients: Seventeen patients with clinical and biochemical features of Cushing’s syndrome. Methods: After the administration of hCRH, the patients underwent bilateral sequential inferior petrosal sinus sampling, with a single blood sample obtained from each of the inferior petrosal sinuses sequentially, along with a peripheral venous sample. The petrosal sinus catheter was withdrawn immediately after obtaining a blood sample. Patients did not require indwelling catheters in the petrosal sinuses, nor heparinisation. Results: Bilateral sequential inferior petrosal sinus sampling correctly identified a pituitary source of ACTH, as shown by a central to peripheral ACTH ratio >2, in all patients in whom the procedure was successfully carried out. All patients underwent transsphenoidal pituitary surgery resulting in remission. Conclusions: The simplified method of inferior petrosal sinus sampling, using a single sequential sample from each of the inferior petrosal sinuses, following initial hCRH stimulation, is as accurate as the more complex test using multiple bilateral simultaneous inferior petrosal sinus samples. It avoids the use of indwelling cerebral venous catheters and is therefore unlikely to cause brain stem damage. European Journal of Endocrinlogy 139 161–166 Introduction The differential diagnosis of Cushing’s syndrome, in particular the differentiation of pituitary-dependent adrenocorticotrophin (ACTH) hypersecretion from ecto- pic ACTH secretion, is often difficult. Pituitary imaging with computed tomography or magnetic resonance scanning sometimes identifies an adenoma but the results may be misleading due to high false positive and false negative results. Identifying an ACTH gradient between inferior petrosal sinuses and the peripheral blood is at present the most accurate method of identifying a pituitary source of ACTH hypersecretion (1). This is done by sampling both inferior petrosal sinuses simultaneously for ACTH, using pre-placed catheters, before and after the administration of corticotrophin-releasing hormone (CRH). The demon- stration of a central to peripheral gradient in the concentration of ACTH in a hypercortisolaemic patient is diagnostic of a pituitary source of ACTH hypersecre- tion. Bilateral simultaneous inferior petrosal sinus sampling (BSimIPSS) as presently carried out is technically demanding in time and materials and carries a small risk. Cavernous sinus sampling (2, 3), developed to improve diagnostic accuracy, is even more invasive and complex but provides no advantage over inferior petrosal sinus sampling (4). Jugular venous sampling is less invasive but also less sensitive (5). We have simplified inferior petrosal sinus sampling to make it easier, cheaper and potentially a safer procedure, without any loss in diagnostic accuracy. Patients and methods Patients Seventeen consecutive patients referred to the endo- crine service were studied prospectively. There were 4 males and 13 females with a mean age of 38 years (range 22–73) (Table 1). The patients had history and clinical findings typical of Cushing’s syndrome. After 2 European Journal of Endocrinology (1998) 139 161–166 ISSN 0804-4643  1998 Society of the European Journal of Endocrinology