This single-center retrospective cohort study represents the first report from an Asian population to evaluate the diagnostic utility of bilateral inferior petrosal sinus sampling (BIPSS) in patients with adrenocorticotropin (ACTH)-dependent Cushing syndrome (CS).

In this retrospective cohort (2021–2025), twenty-four patients with newly diagnosed ACTH-dependent CS at Taipei Veterans General Hospital underwent BIPSS, with blood samples collected from the right and left inferior petrosal sinuses (IPS) and a peripheral vein before and after desmopressin (DDAVP) stimulation. ACTH levels were measured to calculate central-to-peripheral ACTH ratios for diagnostic purposes. The procedure was well tolerated, with no significant complications observed.

Histopathology confirmed Cushing Disease (CD) in nineteen patients and ectopic ACTH syndrome (EAS) in five. Without DDAVP stimulation, BIPSS achieved a sensitivity of 94.7%, specificity of 80.0%, positive predictive value (PPV) of 94.7%, negative predictive value (NPV) of 80.0%, and overall accuracy of 91.7%. Following DDAVP stimulation, diagnostic accuracy reached 100% across all parameters. However, when formally assessed by McNemar’s test, this improvement was not statistically significant. In contrast, pituitary magnetic resonance imaging (MRI) showed lower diagnostic performance (sensitivity: 89.8%, specificity: 60.0%, accuracy: 83.3%). Furthermore, BIPSS correctly predicted adenoma lateralization in 66.6% of CD patients, providing additional surgical guidance.

As the first cohort reported from an Asian population, these findings may help refine our understanding of potential ethnic or population-specific differences in the diagnostic performance of BIPSS. The results support BIPSS, as a safe and highly reliable tool for differential diagnosis in ACTH-dependent CS.