Berneis K, Staub J J, Gessler A, Meier C, Girard J, Müller B
Division of Endocrinology, Diabetology and Clinical Nutrition, Department of Internal Medicine, University Hospitals, CH-4031 Basel, Switzerland.
J Clin Endocrinol Metab. 2002 Dec;87(12):5470-5. doi: 10.1210/jc.2001-011959.
The metyrapone test is used to test the hypothalamic-pituitary-adrenocortical axis. The present study aims to assess the diagnostic accuracy of combined stimulation of ACTH and compound-S (CMP-S). In addition, we analyzed the safety and practicability of this test as an outpatient procedure. A total of 327 metyrapone tests were analyzed retrospectively in 185 patients (mean age, 50.3 +/- 15.2 yr). One hundred thirteen patients had one test, and 72 patients had between 2 and 6 tests over 1-3 yr. Most patients suffered from pituitary adenomas (60 macroadenomas, 63 microadenomas) or other pituitary lesions (n = 29). Metyrapone (2 g) was given at 2400 h as an outpatient procedure. Blood samples for analysis of ACTH, CMP-S, and cortisol were taken at 0730 h. Stimulation of adrenal CMP-S and cortisol by pituitary ACTH demonstrated a dose-response curve with the shape of half a geometric parabola. CMP-S reached a plateau when ACTH rose above 175 ng/liter [r = 0.661, P < 0.0001 for ACTH <175 ng/liter; r = 0.083, P = not significant (NS) for ACTH >175 ng/liter], cortisol flattened at ACTH levels above 230 ng/liter (r = 0.633; P < 0.0001 for ACTH < 230 ng/liter; P = NS for ACTH >230 ng/liter). Alternatively, the sum of CMP-S plus cortisol also flattened when ACTH rose above 230 ng/liter (r = 0.696; P < 0.0001 for ACTH <230; P = NS for ACTH > 230 ng/liter). Receiver operating curve analysis defining a cut-off for ACTH at 150 ng/liter demonstrated a sensitivity of 47% and 67% at a cut-off level for CMP-S at 200 or 260 nmol/liter, respectively. The respective specificity was 82% and 68% for CMP-S. This compared with a sensitivity of 71% and specificity of 69% if the sum of CMP-S plus cortisol of 450 nmol/liter were used as cut-off. The response curve between CMP-S and ACTH implies a maximally stimulated adrenal cortex at circulating ACTH levels above 175 ng/liter. Single measurement of CMP-S using the cut-off at 200 nmol/liter, as suggested in the literature, yields a poor sensitivity of only 47% compared with ACTH. Despite the relatively high cross-reactivity of CMP-S in the cortisol assay, the sum of CMP-S and cortisol levels with a cut-off value of 450 nmol/liter yields a better diagnostic accuracy compared with CMP-S alone.
甲吡酮试验用于检测下丘脑 - 垂体 - 肾上腺皮质轴。本研究旨在评估促肾上腺皮质激素（ACTH）和化合物S（CMP - S）联合刺激的诊断准确性。此外，我们分析了该试验作为门诊程序的安全性和实用性。回顾性分析了185例患者（平均年龄50.3±15.2岁）的327次甲吡酮试验。113例患者进行了1次试验，72例患者在1 - 3年内进行了2至6次试验。大多数患者患有垂体腺瘤（60例大腺瘤，63例微腺瘤）或其他垂体病变（n = 29）。作为门诊程序，在24:00给予甲吡酮（2g）。于07:30采集血样分析ACTH、CMP - S和皮质醇。垂体ACTH对肾上腺CMP - S和皮质醇的刺激呈现出半条几何抛物线形状的剂量反应曲线。当ACTH升至高于175 ng/升时，CMP - S达到平台期[r = 0.661，ACTH <175 ng/升时P <0.0001；r = 0.083，ACTH >175 ng/升时P =无显著性差异（NS）]，当ACTH水平高于230 ng/升时，皮质醇趋于平稳（r = 0.633；ACTH <230 ng/升时P <0.0001；ACTH >230 ng/升时P = NS）。或者，当ACTH升至高于230 ng/升时，CMP - S加皮质醇的总和也趋于平稳（r = 0.696；ACTH <230时P <0.0001；ACTH > 230时P = NS）。将ACTH的临界值定义为150 ng/升的受试者工作特征曲线分析表明，当CMP - S的临界水平分别为200或260 nmol/升时，敏感性分别为47%和67%。CMP - S的相应特异性分别为82%和68%。相比之下，如果将CMP - S加皮质醇的总和450 nmol/升用作临界值，敏感性为71%，特异性为69%。CMP - S与ACTH之间的反应曲线表明，循环ACTH水平高于175 ng/升时肾上腺皮质受到最大刺激。如文献中所建议的，使用200 nmol/升的临界值单次测量CMP - S，与ACTH相比，敏感性仅为47%，较差。尽管CMP - S在皮质醇测定中具有相对较高的交叉反应性，但与单独使用CMP - S相比，临界值为450 nmol/升的CMP - S和皮质醇水平总和具有更好的诊断准确性。
