Background: BIPSS is considered the gold-standard procedure for differentiating autonomous pituitary [Cushings Disease (CD)] and ectopic ACTH syndrome (EAS) sources of ACTH hypersecretion. A basal (i.e. unstimulated) pituitary:peripheral ACTH ratio >2, and/or a CRH stimulated pituitary:peripheral ACTH ratio >3, have been proposed as indicative of CD, with a range of sensitivities and specificities cited in the literature. Additionally, in CD a peak interpetrosal gradient of >1.4 has been reported to predict the side of the adenoma in approximately 2/3 of cases. We have re-examined the accuracy of these diagnostic thresholds in a cohort of patients undergoing BIPSS in our centre over the last 12 years, in whom confirmation of the underlying diagnosis was subsequently established.
Methods: 41 patients with biochemically proven ACTH-dependent Cushings syndrome, who had undergone BIPSS and had either subsequent histological confirmation of the ACTH source or significant improvement/cure of their Cushings were included in the study.
Results: Based on pre-CRH stimulation results, 90% of patients were deemed to have pituitary Cushings and 10% EAS. Post-CRH stimulation, 95% of patients reached the cut-off for CD. These yielded a sensitivity of 97% and a specificity of 100% for pre-CRH stimulation and 100% sensitivity and 67% specificity for post-CRH stimulation. The majority of BIPSS procedures lateralized to the right side (65%), but at surgery this was found to be correct in only half of cases. On the contrary, left lateralization had a much higher positive predictive value (80%). Overall, lateralization was accurate in 60% of cases.
Conclusion: Predominance of right sided lateralization on BIPSS is frequently (1:2) misleading. We propose that additional localizing strategies are pursued prior to pituitary surgery, such as detailed MRI sequences (e.g. SPGR MRI) or functional imaging modalities (e.g. 11C-Methionine PET). Whole gland exploration is particularly important for patients with inconclusive pre-operative localizing investigations.