Lower Cutoffs Improve the Diagnostic Performance of Desmopressin-Stimulated Bilateral Inferior Petrosal Sinus Sampling for Cushing Disease: A Prospective Cohort Study.

OBJECTIVE

To prospectively evaluate the diagnostic performance of traditional versus optimized adrenocorticotropic hormone (ACTH) ratio cutoffs for desmopressin (DDAVP)-stimulated bilateral inferior petrosal sinus sampling (BIPSS) in differentiating Cushing disease (CD) from ectopic ACTH syndrome (EAS) in ACTH-dependent Cushing syndrome.

METHODS

We conducted a prospective single-center observational cohort study of 181 consecutive patients undergoing DDAVP-stimulated BIPSS in a high-volume tertiary pituitary center (Peking Union Medical College Hospital) in China between October 2023 and December 2024. Final diagnosis was confirmed by histopathology and/or biochemical remission. Diagnostic accuracy of traditional cutoffs (basal IPS:P >2.0 or stimulated >3.0) versus optimized cutoffs (determined by receiver operating characteristic curve analysis) was compared.

RESULTS

Among 167 patients with definitive diagnosis (153 CD, 14 EAS), BIPSS showed excellent overall discrimination (area under the curve, 0.994). Traditional cutoffs yielded a sensitivity of 91.5% and specificity of 100.0%. Lower cutoffs (basal IPS:P >1.49 or peak stimulated IPS:P >2.26) improved sensitivity to 97.4% while maintaining 100.0% specificity. Most peak IPS: P values occurred at 3 to 5 min post-DDAVP. False-negative results were associated with absent intersinus lateralization and low IPS ACTH levels, suggesting technical or anatomic sampling limitations rather than impaired DDAVP responsiveness.

CONCLUSION

DDAVP-stimulated BIPSS showed excellent diagnostic performance for differentiating CD from EAS and provides a practical alternative stimulation strategy when corticotropin-releasing hormone is unavailable. Lower DDAVP-specific ACTH ratio cutoffs improved sensitivity without compromising specificity and may reduce false-negative diagnoses of CD in patients with ACTH-dependent Cushing syndrome.