Revamped Perspective on Conventional Interpretation : The Foreboding Prognostic Significance of Low - Lateralization in Inferior Petrosal Sinus Sampling for Cushing's Disease Diagnosis

Context Bilateral inferior petrosal sinus sampling (BIPSS) is widely used to differentially diagnose ectopic ACTH syndrome (EAS) and Cushing’s disease (CD) with pituitary lesions less than 6 mm on MRI. Purpose This study aimed to investigate the diagnostic accuracy of BIPSS and prognosis for low-lateralization (lateralization ratio of bilateral IPS ≤ 1.4) CD with microadenoma (≤ 6 mm). Methods A single-center retrospective study (2011–2019) included 25 EAS and 179 CD (≤ 6 mm) patients, whose diagnosis were confirmed by pathology. All the CD patients received two to ten years follow-up. Results According to multivariable regression, false-negative diagnosis at baseline might be associated with lateralization ratio ≤ 1.4 (adjusted OR = 12.69, 95%CI 4.14–38.86, P  < 0.001). CD patients were divided into the low-lateralization group (lateralization ratio ≤ 1.4) and the high-lateralization group (> 1.4). IPS:P ≥ 2.0 produced sensitivity of 55.0% (39.8%-69.3%) for low-lateralization group (n = 40) to diagnose CD, lower than sensitivity of 93.5% (88.2%-96.6%) for high-lateralization group (n = 139) ( P  < 0.001). Survival analysis showed a higher hazard of nonremission after surgery in low-lateralization group than high-lateralization group (hazard ratio = 3.636, 95%CI 1.456–9.080, P  = 0.006). The incidence of impaired pituitary function after surgery in low-lateralization group was higher than high-lateralization group (median (IQR) 1 (0,2) vs. 0 (0,1), P  = 0.038). Conclusion Lower diagnostic accuracy and worser surgical outcomes were found for low-lateralization group, with more likely nonremission and more impaired pituitary function after pituitary surgery.