Stimulatory effect of adrenocorticotropin on cortisol, aldosterone, and dehydroepiandrosterone secretion in normal humans: Dose-response study
Stimulatory effect of adrenocorticotropin on cortisol, aldosterone, and dehydroepiandrosterone secretion in normal humans: Dose-response study
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DOI：
10.1210/jc.85.9.3141
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发表时间：
2000-09-01
影响因子：
5.8
通讯作者：
Ghigo, E
中科院分区：
文献类型：
--
作者：
Arvat, E;Di Vito, L;Ghigo, E
短促肾上腺皮质激素试验在临床实践中广泛用于诊断肾上腺功能不全。虽然据报道1.0 μ g ACTH剂量对正常受试者的皮质醇水平具有最大的刺激作用，但经典的方法是给予250.0 μ g ACTH（1 - 24）。我们的目的是确定最大和最小刺激剂量的促肾上腺皮质激素对皮质醇，醛固酮，脱氢表雄酮（DHEA）在人类。为了达到这个目的，在12名正常志愿者中，（6男6女;年龄22 - 34岁;体重指数20 - 25公斤/米2）;体表面积1.6 - 1.9 m（2）），我们研究了八种ACTH剂量的剂量反应效应（0.01、0.03、0.06、0.125、0.5、1.0、25.0和250.0 μ g）对皮质醇、醛固酮和DHEA水平的影响。在0分钟给予每一剂量ACTH后，在+60分钟给予第二剂量250.0 μ g ACTH。除0.01 μ g外，所有剂量ACTH后的皮质醇Delta反应曲线下面积（Delta AUC）均显著高于（P <0.02）安慰剂后的皮质醇Delta反应曲线下面积（Delta AUC），显示出明确的剂量-反应关系（P <0.001）。0.03和1.0 μ g ACTH分别为最小和最大有效剂量。用0.01、0.03和0.06 μ g ACTH预处理对250.0 μ g ACTH的皮质醇反应没有改变，而随着ACTH预处理剂量的增加，皮质醇反应逐渐降低（P <0.001）。除0.01 μ g ACTH剂量外，其他剂量的醛固酮Δ AUC均显著高于安慰剂组（P <0.02），显示出明显的剂量-反应关系（P <0.001）。0.03 μ g的剂量是最小有效刺激剂量，而25.0 μ g显示出与250.0 μ g相同的醛固酮释放效果。用安慰剂预处理的250.0 μ g ACTH对醛固酮的反应，用0.01和0.03 μ g ACTH预处理没有改变，而增加ACTH预处理的剂量则降低了醛固酮的反应（P <0.05 - 0.02）。所有剂量ACTH的DHEA Delta AUC均显著高于安慰剂组（P <0.01），显示出明显的剂量-反应关系（P <0.001）。0.01和1.0 μ g ACTH分别为最小和最大有效剂量。用0.01、0.03、0.06和0.125 μ g ACTH预处理对250.0 μ g ACTH的DHEA反应没有改变，而用0.5、1.0和25.0 μ g ACTH预处理则逐渐降低（P <0.01）。总之，这些结果表明，一个非常低的ACTH剂量需要刺激肾上腺皮质类固醇，其中，DHEA似乎是最敏感的促肾上腺皮质激素刺激。
The short ACTH test is widely used in clinical practice for the diagnosis of adrenal insufficiency. It is classically performed administering 250.0 mu g ACTH(1-24) although 1.0 mu g ACTH dose has been reported having maximal stimulatory effect on cortisol levels in normal subjects. We aimed to define the maximal and the minimal stimulatory ACTH dose on cortisol, aldosterone, and dehydroepiandrosterone (DHEA) in humans. To this goal, in 12 normal volunteers (6 males and 6 females; age, 22-34 yr; body mass index 20-25 kg/m(2); body surface 1.6-1.9 m(2)), we studied the dose-response effect of eight ACTH doses (0.01, 0.03, 0.06, 0.125, 0.5, 1.0, 25.0, and 250.0 mu g) on cortisol, aldosterone, and DHEA levels. Each ACTH dose administered at 0 min was followed by a second ACTH dose of 250.0 mu g at +60 min. The cortisol Delta areas under response curve (Delta AUCs) after all ACTH doses, apart from 0.01 mu g, were significantly higher (P < 0.02) than that after placebo, showing a clear dose-response relationship (P < 0.001). The doses of 0.03 and 1.0 mu g ACTH were the minimal and maximal effective doses, respectively. The cortisol response to 250.0 mu g ACTH was not modified by pretreatment with 0.01, 0.03, and 0.06 mu g ACTH doses, whereas it was progressively reduced by increasing the dose of ACTH pretreatment (P < 0.001). The aldosterone Delta AUCs to all but 0.01 mu g ACTH doses were significantly higher (P < 0.02) than that after placebo, showing a clear dose-response relationship (P < 0.001). The dose of 0.03 mu g was the minimal effective stimulating dose, whereas 25.0 pg showed the same aldosterone-releasing effect of 250.0 mu g. The aldosterone response to 250.0 mu g ACTH, preceeded by placebo, was not modified by pretreatment with 0.01 and 0.03 mu g ACTH doses, whereas it was reduced by increasing the dose of ACTH pretreatment (P < 0.05-0.02). The DHEA Delta AUCs to all ACTH doses were significantly higher (P < 0.01) than that after placebo, showing a clear dose-response relationship (P < 0.001). The doses of 0.01 and 1.0 mu g ACTH were the minimal and maximal effective dose, respectively. The DHEA response to 250.0 mu g ACTH was not modified by pretreatment with 0.01, 0.03, 0.06, and 0.125 mu g ACTH doses, whereas it was progressively reduced by pretreatment with 0.5, 1.0, and 25.0 mu g ACTH doses (P < 0.01). In conclusion, these results show that an extremely low ACTH dose is needed to stimulate adrenal steroids and, among them, DHEA seems the most sensitive to corticotropin stimulation.