Pecori Giraldi F, Invitti C, Cavagnini F
University of Milan, Istituto Scientifico Ospedale San Luca, Istituto Auxologico Italiano IRCCS, Milan, Italy.
Clin Endocrinol (Oxf). 2001 May;54(5):601-7. doi: 10.1046/j.1365-2265.2001.01258.x.
Stimulation with corticotropin-releasing hormone (CRH) is one of principal tools for the differential diagnosis of ACTH-dependent Cushing's syndrome. However, different dosages and species of CRH may be employed; further, ACTH levels can be measured by radioimmunoassay (RIA) or immunoradiometric assay (IRMA). The aims of the present study were to perform a reappraisal of the diagnostic accuracy of the CRH test taking these different testing modalities into consideration and to study the correlation between basal ACTH and cortisol levels and their responses to CRH in patients with Cushing's disease.
The study population comprised 148 patients with Cushing's disease and 12 patients with ectopic ACTH secretion collected through an Italian multicentre study.
Patients were submitted to stimulation with 100 microg human or ovine CRH (36% and 64% of subjects, respectively) and ACTH measured either by RIA or IRMA (28% and 72%, respectively). A 50% increase in ACTH and cortisol levels was considered indicative of Cushing's disease.
Mean peak ACTH levels measured by RIA and IRMA were comparable, as was the diagnostic accuracy of the test with the two assays (87% for IRMA and 84% for RIA, ns). In patients with Cushing's disease, stimulation with ovine CRH induced greater hormonal responses compared to testing with human CRH although only the cortisol response reached statistical significance (ACTH: 247.5 +/- 28.0% vs. 168.5 +/- 21.3% over baseline, P = 0.06; cortisol: 89.3 +/- 8.5% vs. 60.8 +/- 9.6% over baseline, P < 0.05 for ovine and human CRH, respectively). No appreciable rise in ACTH and cortisol levels was registered among patients with ectopic ACTH secretion. Diagnostic accuracy of the cortisol response was significantly greater with the ovine than with human peptide (71% vs. 49%, P < 0.05, for ovine and human CRH, respectively) while the ACTH response yielded equal diagnostic accuracy (86% vs. 87%, ns, for the ovine and human peptide, respectively). Interestingly, the correlation between ACTH and cortisol peak responses in patients with Cushing's disease was significantly greater for human than for ovine CRH (r = 0.68 vs. r = 0.41, P < 0.01, respectively). In addition, baseline cortisol levels exhibited a significant negative correlation with both the ACTH and cortisol response to CRH suggesting the persistence of the negative cortisol feedback in patients with Cushing's disease.
(A) Both RIA and IRMA can be used indifferently for the assessment of the ACTH response to CRH. (B) Human and ovine CRH provide the same diagnostic accuracy as regards the ACTH response which, incidentally, represents the most accurate criterion for the evaluation of the CRH test; ovine CRH is superior to the human peptide in the evaluation of the cortisol response. (C) In patients with Cushing's disease, endogenous cortisol maintains the ability to negatively modulate CRH-stimulated corticotropin secretion.
促肾上腺皮质激素释放激素（CRH）刺激试验是促肾上腺皮质激素（ACTH）依赖性库欣综合征鉴别诊断的主要手段之一。然而，CRH的使用剂量和种类可能有所不同；此外，ACTH水平可通过放射免疫分析（RIA）或免疫放射分析（IRMA）进行测定。本研究的目的是综合考虑这些不同的检测方式，重新评估CRH试验的诊断准确性，并研究库欣病患者基础ACTH和皮质醇水平与其对CRH反应之间的相关性。
研究人群包括通过一项意大利多中心研究收集的148例库欣病患者和12例异位ACTH分泌患者。
患者接受100μg人或羊CRH刺激（分别占受试者的36%和64%），并通过RIA或IRMA测定ACTH（分别占28%和72%）。ACTH和皮质醇水平升高50%被认为提示库欣病。
RIA和IRMA测定的平均ACTH峰值水平相当，两种检测方法的试验诊断准确性也相当（IRMA为87%，RIA为84%，无显著差异）。在库欣病患者中，与用人CRH检测相比，用羊CRH刺激诱导的激素反应更大，尽管只有皮质醇反应达到统计学显著性（ACTH：相对于基线升高247.5±28.0% vs. 168.5±21.3%，P = 0.06；皮质醇：相对于基线升高89.3±8.5% vs. 60.8±9.6%，羊和人CRH分别为P < 0.05）。异位ACTH分泌患者中未观察到ACTH和皮质醇水平有明显升高。羊CRH的皮质醇反应诊断准确性显著高于人肽（分别为71%和49%，P < 0.05），而ACTH反应的诊断准确性相当（分别为86%和87%，无显著差异）。有趣的是，库欣病患者中，人CRH的ACTH和皮质醇峰值反应之间的相关性显著高于羊CRH（r分别为0.68和0.41，P < 0.01）。此外，基础皮质醇水平与ACTH和皮质醇对CRH的反应均呈显著负相关，提示库欣病患者中皮质醇负反馈持续存在。
（A）RIA和IRMA均可用于评估ACTH对CRH的反应。（B）人及羊CRH在ACTH反应方面具有相同的诊断准确性，顺便说一句，ACTH反应是评估CRH试验最准确的标准；在评估皮质醇反应方面，羊CRH优于人肽。（C）在库欣病患者中，内源性皮质醇保持对CRH刺激的促肾上腺皮质激素分泌进行负调节的能力。
