Context: During bilateral inferior petrosal sinus sampling (BIPSS), the side-to-side adrenocorticotropic hormone (ACTH) ratio, referred to as , was used to predict pituitary adenoma localization.

Objective: To investigate the potential different diagnostic accuracy of BIPSS for differentiating Cushing disease (CD) and ectopic ACTH secretory syndrome (EAS) patients with low lateralization (inferior petrosal sinus [IPS]:IPS ≤ 1.4) and high lateralization (IPS:IPS > 1.4).

Methods: This single-center retrospective study (2011-2021) included (all patients had BIPSS results and confirmed pathologic diagnoses) 220 consecutive CD patients (validation set), 30 EAS patients, and 40 of the CD patients who had digital subtraction angiography (DSA) videos (discovery set).

Results: In the discovery set, the low-lateralization CD group (n = 11) had a higher median plasma ACTH concentration (62.2, IQR 44.7-181.0 ng/L) than the high-lateralization CD group (n = 29) (33.0, IQR 18.5-59.5, = .013). Lower IPS to peripheral ratios were observed in the low-lateralization group during BIPSS, both before and after stimulation ( = .013 and = .028). The sensitivity of BIPSS before stimulation in differentiating CD from EAS was lower in the low-lateralization group than the high-lateralization group (54.6% vs 93.1%, = .003), as validated in the validation set. DSA videos revealed higher vascular area difference visible in the 2 sides of the pituitary in low lateralization (median 1.2 × 10 pixels, IQR 0.5-1.8) than the high-lateralization group (0.4 × 10 pixels, IQR 0.1-0.7, = .008). The vascular area ratio of the 2 sides was also significantly higher in low (1.55, IQR 1.31-2.20) than high lateralization (1.19, IQR 1.07-1.35, = .010).

Conclusion: Our study suggested that low lateralization in CD patients may reduce the diagnostic sensitivity of BIPSS, which might be potentially associated with peripituitary vascular anatomy.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10989187PMC
http://dx.doi.org/10.1210/jendso/bvae056DOI Listing

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