Dickstein G, DeBold C R, Gaitan D, DeCherney G S, Jackson R V, Sheldon W R, Nicholson W E, Orth D N
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
J Clin Endocrinol Metab. 1996 Aug;81(8):2934-41. doi: 10.1210/jcem.81.8.8768855.
The CRH test may sometimes be useful in the differential diagnosis of Cushing's syndrome, because most patients with pituitary ACTH-dependent Cushing's syndrome (Cushing's disease) respond to CRH, but those with other causes of Cushing's syndrome usually do not. However, about 10% of Cushing's disease patients fail to respond to CRH. We wondered if we could eliminate these false negative results either by exploiting the potential additive or synergistic effects of another ACTH secretagogue or by reducing glucocorticoid inhibition of CRH's ACTH-releasing effect. We compared the effect on plasma ACTH and cortisol in 51 patients with Cushing's disease of administering ovine CRH (1 microgram/kg BW, i.v.) alone, arginine vasopressin (AVP; 10 U, i.m.) alone, the combination of CRH and AVP, and CRH after pretreatment with metyrapone (1 g, orally, every 4 h for three doses; CRH + MET). The rates of nonresponse (ACTH increment, < 35%; cortisol increment, < 20%) to AVP and CRH alone were 26% and 8%, respectively; all patients responded to CRH + AVP. The lack of response was not due to improper administration or rapid metabolism of the agonist, because plasma CRH and AVP concentrations were similar in responders and nonresponders. A synergistic ACTH response to CRH + AVP occurred in 65% of the patients. MET pretreatment increased basal plasma ACTH levels in most patients and induced the greatest mean peak ACTH response to CRH, but 8% of the patients did not respond to CRH + MET with an ACTH increment of 35% or more. Because all of the Cushing's disease patients tested in this study responded to the combination of CRH + AVP, whereas 8% failed to respond to CRH alone, we conclude that CRH + AVP administration may provide a more reliable test for the differential diagnosis of ACTH-dependent Cushing's syndrome than administration of CRH alone. Whether this improved sensitivity is accompanied by unaltered specificity for Cushing's disease must be tested in patients with chronic ectopic ACTH syndrome.
促肾上腺皮质激素释放激素（CRH）试验有时在库欣综合征的鉴别诊断中可能有用，因为大多数垂体促肾上腺皮质激素（ACTH）依赖性库欣综合征（库欣病）患者对CRH有反应，但其他原因导致的库欣综合征患者通常无反应。然而，约10%的库欣病患者对CRH无反应。我们想知道能否通过利用另一种ACTH促分泌剂的潜在相加或协同作用，或通过减少糖皮质激素对CRH促ACTH释放作用的抑制来消除这些假阴性结果。我们比较了单独给予绵羊CRH（1微克/千克体重，静脉注射）、单独给予精氨酸加压素（AVP；10单位，肌肉注射）、CRH与AVP联合应用以及在美替拉酮预处理后给予CRH（1克，口服，每4小时一次，共三剂；CRH + MET）对51例库欣病患者血浆ACTH和皮质醇的影响。单独对AVP和CRH无反应（ACTH增量<35%；皮质醇增量<20%）的比例分别为26%和8%；所有患者对CRH + AVP均有反应。无反应并非由于激动剂给药不当或代谢过快，因为反应者和无反应者的血浆CRH和AVP浓度相似。65%的患者对CRH + AVP出现协同ACTH反应。美替拉酮预处理使大多数患者的基础血浆ACTH水平升高，并诱导出对CRH最大的平均峰值ACTH反应，但8%的患者对CRH + MET无反应，ACTH增量未达到35%或更高。由于本研究中所有接受测试的库欣病患者对CRH + AVP联合应用均有反应，而8%的患者单独对CRH无反应，我们得出结论，与单独给予CRH相比，给予CRH + AVP可能为ACTH依赖性库欣综合征的鉴别诊断提供更可靠的试验。这种提高的敏感性是否伴有对库欣病的特异性不变，必须在慢性异位ACTH综合征患者中进行测试。
