Detomas Mario, Ritzel Katrin, Nasi-Kordhishti Isabella, Schernthaner-Reiter Marie Helene, Losa Marco, Tröger Viola, Altieri Barbara, Kroiss Matthias, Kickuth Ralph, Fassnacht Martin, Micko Alexander, Honegger Jürgen, Reincke Martin, Deutschbein Timo
Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany.
Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
Eur J Endocrinol. 2023 May 18. doi: 10.1093/ejendo/lvad050.
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.
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).
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).
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.
双侧岩下窦采血（BIPSS）被视为区分库欣病（CD）和异位库欣综合征（ECS）的金标准。然而，已发表的数据，如关于额外催乳素分析的诊断价值存在争议。因此，我们在一项多中心研究中评估了有无催乳素情况下BIPSS的诊断性能。
在5个欧洲参考中心进行的回顾性研究。在BIPSS时接受人促肾上腺皮质激素释放激素刺激的明显促肾上腺皮质激素（ACTH）依赖性库欣综合征患者符合条件。通过受试者操作特征分析（参考：CD）计算岩下窦（IPS）与外周（P）ACTH比值以及标准化ACTH：催乳素IPS：P比值的临界值。
共确定了156例接受BIPSS的患者。其中，120例患者（92例（77%）为女性；106例（88%）为CD，14例（12%）为ECS）在手术后有组织病理学确诊的肿瘤或生化缓解和/或肾上腺功能不全；只有该亚组通过ROC分析进行了分析。ACTH IPS：P比值的最佳临界值在基线时≥1.9（敏感性82.1%（95%CI 73.2 - 88.6），特异性85.7%（95%CI 56.2 - 97.5），AUC 0.86），在CRH后5分钟时≥2.1（敏感性91.3%（95%CI 83.6 - 95.7），特异性92.9%（95%CI 64.1 - 99.6），AUC 0.96）。一个亚组进行了额外的催乳素分析。标准化ACTH：催乳素IPS：P比值的最佳临界值计算为≥1.4（敏感性96.0%（95%CI 77.7 - 99.9），特异性100%（95%CI 56.1 - 100），AUC 0.99）。
我们的研究证实了BIPSS在ACTH依赖性库欣综合征鉴别诊断中的高准确性，并表明同时测量催乳素可能进一步提高该检查的诊断性能。
