Tsagarakis S, Vassiliadi D, Kaskarelis I S, Komninos J, Souvatzoglou E, Thalassinos N
Department of Endocrinology, Athens Polyclinic Hospital, Athens, Greece.
J Clin Endocrinol Metab. 2007 Jun;92(6):2080-6. doi: 10.1210/jc.2006-2691. Epub 2007 Mar 13.
Although bilateral inferior petrosal sinus sampling (BIPSS) with CRH stimulation is the most accurate procedure for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS), 4-15% of patients with Cushing's disease (CD) fail to demonstrate diagnostic gradients. Preliminary data suggest that a more potent stimulation by the combined administration of CRH plus desmopressin during BIPSS may provide some diagnostic advantage. A crucial issue, however, is whether such an amplified stimulation may affect the specificity of the procedure, and this was the main aim of the present study.
We investigated the diagnostic accuracy of BIPSS performed by CRH plus desmopressin stimulation.
A retrospective analysis was conducted at a single tertiary care center.
Fifty-four patients were admitted for the investigation of ACTH-dependent CS. CD was diagnosed in 47 patients; occult ectopic ACTH syndrome (oEAS) was histologically confirmed in seven patients.
INTERVENTION(S): All patients underwent BIPSS with CRH plus desmopressin administration. Additional noninvasive tests included CRH test, high-dose dexamethasone suppression test, desmopressin test, and pituitary magnetic resonance imaging.
Gradients of inferior petrosal sinus (IPS) to peripheral (IPS/P) ACTH were calculated before and after stimulation with CRH plus desmopressin.
The sensitivity for a basal IPS/P gradient greater than 2 was 61.7%, with 100% specificity and a diagnostic accuracy of 66.7%. After stimulation with CRH plus desmopressin, receiver operating characteristic (ROC) curve analysis showed that a cutoff gradient of more than 2 offers the best test performance. In total, 46 of 47 patients with CD had an IPS/P gradient greater than 2, but none of the patients with oEAS, resulting in a sensitivity of 97.9%. The specificity was 100%, diagnostic accuracy was 98.2%, and the positive and negative predictive values were 100 and 87.5%, respectively. A subgroup of 18 patients (16 with CD and two with oEAS) had contradictory responses to routine tests with CRH and/or high-dose dexamethasone suppression test; sensitivity, specificity, and accuracy of BIPSS in this subgroup were 100%.
The application of a combined stimulation with CRH plus desmopressin during BIPSS is associated with a high sensitivity but no loss of specificity.
虽然促肾上腺皮质激素释放激素（CRH）刺激下的双侧岩下窦采血（BIPSS）是诊断促肾上腺皮质激素（ACTH）依赖性库欣综合征（CS）最准确的方法，但15%的库欣病（CD）患者未能显示出诊断梯度。初步数据表明，在BIPSS期间联合使用CRH和去氨加压素进行更有效的刺激可能具有一定的诊断优势。然而，一个关键问题是这种增强的刺激是否会影响该方法的特异性，这也是本研究的主要目的。
我们研究了CRH联合去氨加压素刺激下BIPSS的诊断准确性。
在一家三级医疗中心进行回顾性分析。
54例因ACTH依赖性CS入院检查的患者。47例诊断为CD；7例经组织学证实为隐匿性异位ACTH综合征（oEAS）。
所有患者均接受了CRH联合去氨加压素的BIPSS检查。其他非侵入性检查包括CRH试验、大剂量地塞米松抑制试验、去氨加压素试验和垂体磁共振成像。
计算CRH联合去氨加压素刺激前后岩下窦（IPS）与外周血（IPS/P）ACTH的梯度。
基础IPS/P梯度大于2时的敏感性为61.7%，特异性为100%，诊断准确性为66.7%。CRH联合去氨加压素刺激后，受试者工作特征（ROC）曲线分析表明，截断梯度大于2时检测性能最佳。47例CD患者中，共有46例IPS/P梯度大于2，但oEAS患者均无此情况，敏感性为97.9%。特异性为100%，诊断准确性为98.2%，阳性和阴性预测值分别为100%和87.5%。18例患者（16例CD和2例oEAS）对CRH和/或大剂量地塞米松抑制试验的常规检查有矛盾反应；该亚组中BIPSS的敏感性、特异性和准确性均为100%。
BIPSS期间联合使用CRH和去氨加压素刺激具有高敏感性且不损失特异性。
