Outcome of Petrosal Venous Sampling in Consecutive 68 Patients From a Major Neurosurgical Center in the United Kingdom

Background: Cushing’s disease is a challenging endocrine disorder caused by non-physiological cortisol excess from adrenocorticotropic hormone (ACTH) secreting pituitary adenoma. Inferior petrosal venous sampling (IPSS) is considered the gold standard investigation to differentiate Cushing’s disease from ectopic ACTH syndrome. Methods: This retrospective study included all patients who underwent IPSS between January 2011 and October 2020 at The National Hospital for Neurology and Neurosurgery in London. Patients demographics, radiological, surgical, endocrinological and, histological data were retrieved. We assessed the accuracy of IPSS in localizing ACTH secreting pituitary adenoma and its concordance with neuroimaging and surgical findings at the time of tumor resection. Results: In total 68 patients underwent IPSS, 22 males and 46 females. The median age was 42 years. IPSS was performed prior to primary surgery in 61 patients (90%) and before secondary surgery in 4 patients (6%). Three patients (4%) are awaiting surgery at the time of our study. Fifty-two patients (80%) had positive histology of ACTH expressing adenoma. Four patients (8%) had ectopic ACTH syndrome. The sensitivity of IPSS in predicting Cushing’s disease prior to corticotropin-releasing hormone (CRH) stimulation was 91% (95% CI [83% to 97%]) and accuracy of 88% (95% CI [77% to 95%]). The sensitivity of IPSS post CRH administration was 96% (95% CI [87% to 100%]) with accuracy of 86% (95% CI [75% to 93%]). Data on lateralization of pituitary adenoma were available for 63 patients. Prior to CRH stimulation, lateralization was right sided in 35 patients (56%), left sided in 15 (24%), and 13 patients (20%) did not have adequate interpetrosal sinus ACTH ratio. Lateralization post CRH stimulation was right sided in 40 patients (64%), left sided in 20 (32%), and 3 patients (4%) did not achieve adequate ACTH gradient ratio between two sides. Eighteen patients (30%) switched adenoma lateralization between pre and post CRH stimulation. Post CRH IPSS was consistent with neuroradiology in localizing pituitary adenomas in 59% (29 out of 49 patients) and concordant with surgical findings in 41% (25 out of 61 patients). Patients with ectopic ACTH syndrome had negative IPSS at all stages. IPSS procedure failed in 2 patients (3%). No post procedure complications were reported. Conclusion: IPSS has high sensitivity in diagnosing pituitary driven Cushing’s disease with good safety profile. However, the reliability in lateralizing pituitary adenoma is debated. One third of patients in this cohort switched lateralization before and after CRH administration. Studies on monkeys and rats showed that CRH induces coronary vasodilation and reduction in systemic vascular resistance. This suggest that CRH might have vasoactive effect on pituitary blood vessels with subsequent influence on IPS:P ACTH gradient ratio between the two sides.