Arvat E, Di Vito L, Lanfranco F, Maccario M, Baffoni C, Rossetto R, Aimaretti G, Camanni F, Ghigo E
Department of Internal Medicine, University of Turin, Torino, Italy.
J Clin Endocrinol Metab. 2000 Sep;85(9):3141-6. doi: 10.1210/jcem.85.9.6784.
The short ACTH test is widely used in clinical practice for the diagnosis of adrenal insufficiency. It is classically performed administering 250.0 microg ACTH(1-24) although 1.0 microg 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/m2; body surface 1.6-1.9 m2), 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 microg) on cortisol, aldosterone, and DHEA levels. Each ACTH dose administered at 0 min was followed by a second ACTH dose of 250.0 microg at +60 min. The cortisol delta areas under response curve (deltaAUCs) after all ACTH doses, apart from 0.01 microg, 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 microg ACTH were the minimal and maximal effective doses, respectively. The cortisol response to 250.0 microg ACTH was not modified by pretreatment with 0.01, 0.03, and 0.06 microg ACTH doses, whereas it was progressively reduced by increasing the dose of ACTH pretreatment (P < 0.001). The aldosterone deltaAUCs to all but 0.01 microg 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 microg was the minimal effective stimulating dose, whereas 25.0 microg showed the same aldosterone-releasing effect of 250.0 microg. The aldosterone response to 250.0 microg ACTH, preceeded by placebo, was not modified by pretreatment with 0.01 and 0.03 microg ACTH doses, whereas it was reduced by increasing the dose of ACTH pretreatment (P < 0.05-0.02). The DHEA deltaAUCs 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 microg ACTH were the minimal and maximal effective dose, respectively. The DHEA response to 250.0 microg ACTH was not modified by pretreatment with 0.01, 0.03, 0.06, and 0.125 microg ACTH doses, whereas it was progressively reduced by pretreatment with 0.5, 1.0, and 25.0 microg 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.
短促肾上腺皮质激素（ACTH）试验在临床实践中广泛用于诊断肾上腺功能不全。传统做法是给予250.0微克ACTH（1 - 24），不过有报道称1.0微克ACTH剂量对正常受试者的皮质醇水平具有最大刺激作用。我们旨在确定对人类皮质醇、醛固酮和脱氢表雄酮（DHEA）具有最大和最小刺激作用的ACTH剂量。为实现这一目标，我们对12名正常志愿者（6名男性和6名女性；年龄22 - 34岁；体重指数20 - 25 kg/m²；体表面积1.6 - 1.9 m²）进行研究，观察了八种ACTH剂量（0.01、0.03、0.06、0.125、0.5、1.0、25.0和250.0微克）对皮质醇、醛固酮和DHEA水平的剂量 - 反应效应。在0分钟给予每种ACTH剂量后，于+60分钟给予第二次250.0微克的ACTH剂量。除0.01微克外，所有ACTH剂量后的皮质醇反应曲线下面积增量（deltaAUCs）均显著高于安慰剂组（P < 0.02），呈现明显的剂量 - 反应关系（P < 0.001）。0.03微克和1.0微克ACTH剂量分别是最小和最大有效剂量。250.0微克ACTH的皮质醇反应不受0.01、0.03和0.06微克ACTH剂量预处理的影响，而随着ACTH预处理剂量增加其反应逐渐降低（P < 0.001）。除0.01微克ACTH剂量外，所有剂量的醛固酮deltaAUCs均显著高于安慰剂组（P < 0.02），呈现明显的剂量 - 反应关系（P < 0.001）。0.03微克是最小有效刺激剂量，而25.0微克与250.0微克具有相同的醛固酮释放效应。在安慰剂预处理后给予250.0微克ACTH，其醛固酮反应不受0.01和0.03微克ACTH剂量预处理的影响，而随着ACTH预处理剂量增加其反应降低（P < 0.05 - 0.02）。所有ACTH剂量后的DHEA deltaAUCs均显著高于安慰剂组（P < 0.01），呈现明显的剂量 - 反应关系（P < 0.001）。0.01微克和1.0微克ACTH剂量分别是最小和最大有效剂量。250.0微克ACTH的DHEA反应不受0.01、0.03、0.06和0.125微克ACTH剂量预处理的影响，而随着0.5、1.0和25.0微克ACTH剂量预处理其反应逐渐降低（P < 0.01）。总之，这些结果表明刺激肾上腺类固醇所需的ACTH剂量极低，其中DHEA似乎对促肾上腺皮质激素刺激最为敏感。
