Tsagarakis S, Tsigos C, Vasiliou V, Tsiotra P, Kaskarelis J, Sotiropoulou C, Raptis S A, Thalassinos N
Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, Athens, Greece.
J Clin Endocrinol Metab. 2002 Apr;87(4):1646-53. doi: 10.1210/jcem.87.4.8358.
The role of desmopressin, alone or in combination with CRH, in the differential diagnosis between Cushing's disease (CD) and ectopic ACTH secretion (EAS) still remains uncertain. Based on existing data, the desmopressin test is regarded as an alternative to the CRH stimulation test and, when given in combination with CRH, it has been suggested to completely discriminate between patients with CD and EAS. However, assessment of these tests has been limited in only a small number of patients with EAS. Desmopressin is a relatively specific V2 vasopressin receptor (V2R) agonist. Although expression of V3 vasopressin receptor (V3R) is common in tumors with EAS, the expression of V2R has not been extensively investigated. In the present study, we report our findings of the desmopressin and the combined CRH-desmopressin test in a series of patients with CD and EAS; also, the expression of V2R and V3R was investigated in tumors with EAS by a RT-PCR method. We assessed a cohort of 31 patients with ACTH-dependent Cushing's syndrome, including 26 patients with CD and five cases with histologically confirmed EAS. To avoid bias of predetermined criteria, univariate curves of the receiver operating characteristics (ROC) were constructed by plotting the sensitivity against 1-specificity at each level of the percent cortisol (F) and ACTH responses to these tests. Following desmopressin administration there was an overlap of the percent F and ACTH responses among patients with CD and EAS, and the area under the ROC curve for both these responses was not significantly different than that occurring by chance. This was also true for the percent F response following the combined CRH-desmopressin test. However, the area under the ROC curve for the percent ACTH rise following the combined test was significantly different; the point of the ROC curve closest to 1 corresponded to a percent ACTH rise of 218% (88% sensitivity and 80% specificity). Expression of V2R and V3R mRNA was investigated in four of the five excised tumors with EAS and revealed the presence of the V2R in all, whereas the V3R mRNA was expressed in three of these cases. In conclusion, in this series the desmopressin test produced a significant overlap of responses between CD and patients with EAS and, therefore, is of limited value in the differential diagnosis of the ACTH-dependent Cushing's syndrome. This is most probably due to the expression of the V2R in tumors with EAS. Moreover, following the combined CRH-desmopressin test only the ACTH but not the F responses were diagnostically useful, but still far from completely discriminating patients with CD and EAS.
去氨加压素单独或联合促肾上腺皮质激素释放激素（CRH）在库欣病（CD）和异位促肾上腺皮质激素（ACTH）分泌（EAS）的鉴别诊断中的作用仍不确定。基于现有数据，去氨加压素试验被视为CRH刺激试验的替代方法，并且当与CRH联合使用时，有人提出它可以完全区分CD患者和EAS患者。然而，这些试验的评估仅在少数EAS患者中进行。去氨加压素是一种相对特异的血管加压素V2受体（V2R）激动剂。虽然血管加压素V3受体（V3R）在EAS肿瘤中普遍表达，但V2R的表达尚未得到广泛研究。在本研究中，我们报告了我们对一系列CD和EAS患者进行去氨加压素及联合CRH-去氨加压素试验的结果；此外，通过逆转录聚合酶链反应（RT-PCR）方法研究了EAS肿瘤中V2R和V3R的表达。我们评估了31例促肾上腺皮质激素依赖性库欣综合征患者，包括26例CD患者和5例经组织学证实的EAS患者。为避免预定标准的偏差，通过绘制皮质醇（F）百分比和ACTH对这些试验反应的每个水平下的敏感性与1-特异性的关系，构建了受试者操作特征（ROC）的单变量曲线。给予去氨加压素后，CD患者和EAS患者的F百分比和ACTH反应存在重叠，并且这两种反应的ROC曲线下面积与偶然发生的情况相比无显著差异。联合CRH-去氨加压素试验后的F百分比反应也是如此。然而，联合试验后ACTH升高百分比的ROC曲线下面积有显著差异；ROC曲线最接近1的点对应的ACTH升高百分比为218%（敏感性88%，特异性80%）。在5例切除的EAS肿瘤中的4例中研究了V2R和V3R mRNA的表达，结果显示所有肿瘤中均存在V2R，而其中3例表达V3R mRNA。总之，在本系列研究中，去氨加压素试验在CD和EAS患者之间产生了显著的反应重叠，因此在促肾上腺皮质激素依赖性库欣综合征的鉴别诊断中价值有限。这很可能是由于EAS肿瘤中V2R的表达。此外，联合CRH-去氨加压素试验后，只有ACTH反应而不是F反应在诊断上有用，但仍远不能完全区分CD和EAS患者。
