Revamped perspective on conventional interpretation: the foreboding prognostic significance of low-lateralization in inferior petrosal sinus sampling for diagnosis of Cushing's disease.

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 detected on MRI. PURPOSE: This study aimed to investigate the diagnostic accuracy of BIPSS and prognosis of low-lateralization [lateralization ratio of bilateral inferior petrosal sampling (IPS) ≤ 1.4] CD with microadenoma (≤ 6 mm). METHODS: This single-centre retrospective study (2011-2019) included 25 EAS and 179 CD (microadenoma ≤ 6 mm) patients whose diagnoses were confirmed by pathology. All CD patients received two to ten years of follow-up. RESULTS: According to the multivariable regression results, a false-negative diagnosis at baseline might be associated with a lateralization ratio ≤ 1.4 (adjusted OR = 12.69, 95% CI 4.14-38.86; P < 0.001). CD patients were divided into a low-lateralization group (lateralization ratio ≤ 1.4) and a high-lateralization group (> 1.4). An inferior petrosal sinus-to-peripheral ACTH ratio (IPS: P-ACTH) ≥ 2.0 had a sensitivity of 55.0% (95% CI 39.8%-69.3%) for the low-lateralization group (n = 40), which was lower than the sensitivity of 93.5% (95% CI 88.2%-96.6%) for the high-lateralization group (n = 139) (P < 0.001). CONCLUSION: Lower diagnostic accuracy and poorer surgical outcomes were found for the low-lateralization group, with a lesser likelihood of remission and more impaired pituitary function after pituitary surgery. CLINICAL TRIAL NUMBER: Not applicable.