Optimizing inferior petrosal sinus sampling: results of a multicenter study

Inferior petrosal sinus sampling (IPSS) confirms a central source of adrenocorticotropic hormone (ACTH) secretion in Cushing's disease (CD). We explored IPSS protocols to optimize diagnostic sensitivity and reduce laboratory testing burden. Patients from the multicenter Registry of Adenomas of the Pituitary and Related Disorders (RAPID) who underwent IPSS for management of CD, and in whom central:peripheral (C:P) ACTH levels were evaluated, were included. A total of 93 patients (mean age 44 ± 13 years, 17% male; 78% MRI-negative, 84% long-term remission) were analyzed. At baseline, 77% of patients showed a C:P ACTH ratio ≥2X, and all of these patients reached ≥3X C:P ACTH after stimulation. Among patients with a baseline ratio <2X, 57% (n = 12/21) crossed the ≥3X threshold after stimulation, prolactin normalization confirmed one additional patient, with two further patients remaining indeterminate. Stimulation produced 3.1-, 2.8-, and 1.9-fold increases in C:P ACTH at 2, 5, and 10 min post-stimulation, respectively, with the best response at 2-5 min. Cumulatively, 77%, 79%, 88%, 90%, and 91% of patients met criteria for CD by 0, 2, 5, 10, and 15 min, respectively. In this confirmed-CD cohort these proportions represent test sensitivity, rising from 77.4% (95% CI 67.6-85.4%) at baseline to 91.4% (95% CI 83.8-96.2%) by 15 min. Because all patients had surgically confirmed CD, these values reflect test sensitivity rather than overall diagnostic accuracy. Diagnostic yield plateaued by 15 min with negligible gain thereafter, and baseline together with a limited number of early post-stimulation samples captured most cases. These retrospective, hypothesis-generating findings suggest that a streamlined protocol may reduce laboratory and interpretive burden while preserving sensitivity, pending prospective validation.

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Journal
Journal of Clinical Neuroscience
Published
2026-10-27
DOI
https://doi.org/10.1016/j.jocn.2026.112367
Primary Topic
Pituitary Gland Disorders and Treatments
Type
article
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article

Optimizing inferior petrosal sinus sampling: results of a multicenter study

Kyle C. Wu, Michael J. Karsy, William T. Couldwell, Juan Carlos Fernandez-Miranda et al.
1 links
Journal of Clinical Neuroscience
Pituitary Gland Disorders and Treatments
article

Optimizing inferior petrosal sinus sampling: results of a multicenter study

Kyle C. Wu, Michael J. Karsy, William T. Couldwell, Juan Carlos Fernandez-Miranda, Carolina Benjamin, Albert H. Kim, Varun R. Kshettry, Clayton D. Rawson, Michael P. Catalino, Robert C. Rennert, Donato R. Pacione, Andrew S. Little, Kevin C.J. Yuen, Jamie J. Van Gompel, Michael R. Chicoine, Paul Gardner, Adam N. Mamelak, Sarah Collopy, Garni Barkhoudarian, Daniel M. Prevedello, Julie Martha Silverstein, Nathan Thomas Zwagerman, André Beer Furlan, Gabriel Zada, Samuel A. Tenhoeve, Marvin Bergsneider, James J. Evans, Dan Kelly, Won Kim
article en

Abstract

Inferior petrosal sinus sampling (IPSS) confirms a central source of adrenocorticotropic hormone (ACTH) secretion in Cushing's disease (CD). We explored IPSS protocols to optimize diagnostic sensitivity and reduce laboratory testing burden. Patients from the multicenter Registry of Adenomas of the Pituitary and Related Disorders (RAPID) who underwent IPSS for management of CD, and in whom central:peripheral (C:P) ACTH levels were evaluated, were included. A total of 93 patients (mean age 44 ± 13 years, 17% male; 78% MRI-negative, 84% long-term remission) were analyzed. At baseline, 77% of patients showed a C:P ACTH ratio ≥2X, and all of these patients reached ≥3X C:P ACTH after stimulation. Among patients with a baseline ratio <2X, 57% (n = 12/21) crossed the ≥3X threshold after stimulation, prolactin normalization confirmed one additional patient, with two further patients remaining indeterminate. Stimulation produced 3.1-, 2.8-, and 1.9-fold increases in C:P ACTH at 2, 5, and 10 min post-stimulation, respectively, with the best response at 2-5 min. Cumulatively, 77%, 79%, 88%, 90%, and 91% of patients met criteria for CD by 0, 2, 5, 10, and 15 min, respectively. In this confirmed-CD cohort these proportions represent test sensitivity, rising from 77.4% (95% CI 67.6-85.4%) at baseline to 91.4% (95% CI 83.8-96.2%) by 15 min. Because all patients had surgically confirmed CD, these values reflect test sensitivity rather than overall diagnostic accuracy. Diagnostic yield plateaued by 15 min with negligible gain thereafter, and baseline together with a limited number of early post-stimulation samples captured most cases. These retrospective, hypothesis-generating findings suggest that a streamlined protocol may reduce laboratory and interpretive burden while preserving sensitivity, pending prospective validation.

Journal of Clinical NeuroscienceVol. 155
University of Southern California (US), Cedars-Sinai Medical Center (US), Cleveland Clinic (US), Barrow Neurological Institute (US), St. Joseph's Hospital and Medical Center (US), Mayo Clinic (US), University of Miami (US), Thomas Jefferson University (US), University of California, Los Angeles (US), Medical College of Wisconsin (US), Washington University in St. Louis (US), University of Utah (US), University of South Florida (US), University of Michigan (US), Saint John's Health Center (US), Michigan Medicine (US), University of Pittsburgh Medical Center (US), Noorda College of Osteopathic Medicine (US), University of Virginia (US), The Ohio State University (US), New York University (US), University of Missouri (US), Stanford University (US)
Foundation for Barnes-Jewish Hospital, Barrow Neurological Foundation
Good health and well-being
Openalex Percentile: Top 11%
Pituitary Gland Disorders and Treatments
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