Bilateral inferior petrosal sinus sampling with human CRH stimulation in ACTH-dependent Cushing's syndrome: results from a retrospective multicenter study

Mario Detomas; Katrin Ritzel; Isabella Nasi-Kordhishti; Marie Helene Schernthaner-Reiter; Marco Losa; Viola Tröger; Barbara Altieri; Matthias Kroiss; Ralph Kickuth; Martin Fassnacht; Alexander Micko; Jürgen Honegger; Martin Reincke; Timo Deutschbein

doi:10.1093/ejendo/lvad050

Bilateral inferior petrosal sinus sampling with human CRH stimulation in ACTH-dependent Cushing's syndrome: results from a retrospective multicenter study

Eur J Endocrinol. 2023 May 18:lvad050. doi: 10.1093/ejendo/lvad050. Online ahead of print.

Authors

Affiliations

¹ Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany.
² Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
³ Department of Neurosurgery, University of Tübingen, Tübingen, Germany.
⁴ Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
⁵ Department of Neurosurgery, Istituto Scientifico San Raffaele, Vita-Salute University, Milano, Italy.
⁶ Institute of Diagnostic and Interventional Radiology, University Hospital, University of Würzburg, Würzburg, Germany.
⁷ Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
⁸ Medicover Oldenburg MVZ, Oldenburg, Germany.

PMID: 37200460
DOI: 10.1093/ejendo/lvad050

Abstract

Objective: Bilateral inferior petrosal sinus sampling (BIPSS) is regarded as gold standard to differentiate between Cushing´s disease (CD) and ectopic Cushing's syndrome (ECS). However, published data e.g. on the diagnostic value of additional prolactin analysis is controversial. Thus, we evaluated the diagnostic performance of BIPSS with and without prolactin in a multicenter study.

Design and methods: Retrospective study in 5 European reference centers. Patients with overt adrenocorticotropin (ACTH)-dependent Cushing's syndrome at the time of BIPSS with human corticotropin-releasing hormone stimulation were eligible. Cut-offs for the inferior petrosal sinus (IPS) to peripheral (P) ACTH ratio and the normalized ACTH:prolactin IPS:P ratio were calculated via receiver operator characteristics analyses (reference: CD).

Results: 156 patients with BIPSS were identified. Of these, 120 patients (92 (77%) females; 106 (88%) CD, 14 (12%) ECS) had either histopathologically confirmed tumors or biochemical remission and/or adrenal insufficiency after surgery; only this subgroup was analyzed by ROC analysis. The optimal cut-offs for the ACTH IPS:P ratio were ≥1.9 at baseline (sensitivity 82.1% (95%CI 73.2-88.6), specificity 85.7% (95%CI 56.2-97.5), AUC 0.86) and ≥2.1 at 5 minutes post-CRH (sensitivity 91.3% (95%CI 83.6-95.7), specificity 92.9%(95%CI 64.1-99.6), AUC 0.96). A subgroup underwent additional prolactin analysis. An optimal cut-off of ≥1.4 was calculated for the normalized ACTH:prolactin IPS:P ratio (sensitivity 96.0% (95%CI 77.7-99.9), specificity 100% (95%CI 56.1-100), AUC 0.99).

Conclusion: Our study confirms the high accuracy of BIPSS in the differential diagnosis of ACTH-dependent Cushing's syndrome and suggests that the simultaneous measurement of prolactin might further improve the diagnostic performance of this test.

Keywords: Catheter; Cushing’s disease; IPSS; ectopic; petrosal sinus; pituitary; prolactin.