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

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.

Bilateral inferior petrosal sinus sampling: validity, diagnostic accuracy in lateralization of pituitary microadenoma, and treatment in eleven patients with Cushing’s syndrome – a single-center retrospective cohort study

“…In this investigation, the utilization of Prolactin-normalized ACTH IPS/P ratios exhibited a sensitivity and specificity of 100% for the CD diagnosis. This finding aligns with research conducted by Detomas et al, which reported a sensitivity of 96% and specificity of 100% for the normalized ACTH: Prolactin IPS/P ratio [ 26 ]. It seems that concurrently assessing prolactin levels may potentially enhance the diagnostic accuracy of BIPSS.…”

The diagnostic yield of inferior petrosal sinus sampling in Cushing syndrome in the era of ovine CRH shortage

“…IPSS can accurately differentiate a central pituitary lesion from a peripheral ectopic ACTH source [ 11 ], yet stimulation with oCRH is imperative to increase its correctness [ 25 ]. Namely, with oCRH stimulation, results of IPSS have been associated to robustly confirm or exclude the diagnosis of CD with an 80–100% sensitivity and over 95% specificity [ 12 , 16 , 17 , 22 , 27 ]. Thereby, an asymmetric venous outflow does not appear to significantly affect the precision with which the adenoma side can be predicted [ 4 ], although results after oCRH stimulation show significant differences with larger numerical variations.…”

“…Nonetheless, perhaps owing to the small patient cohort, it does not seem to influence clinical outcomes, at least to a noticeable extent. Very recently, an European multicenter study used human CRH (hCRH) as an alternative stimulant showing a sensitivity of 81.1% (95% CI 72.1–87.8) and a specificity of 85.7% (95% CI 56.2–97.5) applying the conventional cut-off values of ≥ 3 for post-hCRH stimulation, and a sensitivity 94.3% (95% CI 87.6–97.7) and specificity 85.7% (95% 56.1–97.5) using an newly calculated optimized cut-off values of ≥ 2.1 post-hCRH [ 16 ]. Alternatively, desmopressin might be used instead given its availability and easy applicability.…”

Subtyping of Cushing’s Syndrome: A Step Ahead

“…Recently, it has been reported that the simultaneous measurement of prolactin might further improve the diagnostic performance of human CRH stimulated BIPSS: the normalized ACTH to prolactin ratio was able to correctly detect ACTH source in 31 out of 32 confirmed ACTH-dependent CS [34].…”