Geer Eliza B, Landman Rita E, Wardlaw Sharon L, Conwell Irene M, Freda Pamela U
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Pituitary. 2005;8(2):115-22. doi: 10.1007/s11102-005-5227-6.
Nalmefene Stimulation of the HPA Axis.
The Hypothalamic-pituitary-adrenal (HPA) axis plays a vital role in the body's response to stress. The traditional gold standard for evaluating the HPA axis, the insulin hypoglycemia test (IHT), has several known limitations, and a second test, the standard ACTH stimulation test, can detect severe deficiencies of cortisol, but often misses mild or early cases. Therefore, a better test for the evaluation of the HPA axis is needed. This study evaluated the opiate antagonist nalmefene as a stimulation test of the HPA axis.
25 healthy subjects were studied, 9 women and 16 men, mean age 30.4 yr. (range 21-55), and mean BMI 24.1 kg/m2 (range 18.6-34.2). Subjects received one of 3 doses of intravenously administered nalmefene: 2 mg (n = 6), 6 mg (n = 12), or 10 mg (n = 7). Serum cortisol and plasma ACTH were measured before and serially over two hours after the administration of nalmefene.
ACTH and cortisol levels rose significantly and similarly after the 10 mg dose and the 6 mg dose. After the 10 mg dose, mean peak ACTH was 82.4 +/- 22.6 pg/ml and mean peak cortisol was 25.2 +/- 1.8 microg/dl. After the 6 mg dose, mean peak ACTH was 70.3 +/- 7.7 pg/ml and mean peak cortisol was 24.7 +/- 1.7 microg/dl. Cortisol levels rose above 18 microg/dl in all subjects receiving 10 mg of nalmefene, and in all but two of the subjects receiving 6 mg of nalmefene. Side effects to nalmefene were of greater duration and intensity in the subjects receiving 10 mg of nalmefene vs. those receiving 6 or 2 mg. These included most notably fatigue, lightheadedness, nausea and vomiting.
Of the nalmefene doses we studied, 6 mg achieved the best combination of stimulation of ACTH and cortisol and fewest side effects. If further studies show a concordance between nalmefene and IHT, nalmefene testing could be used to assess the HPA axis in patients at risk for dysfunction of this axis.
纳美芬对下丘脑-垂体-肾上腺（HPA）轴的刺激作用
下丘脑-垂体-肾上腺（HPA）轴在机体对应激的反应中起至关重要的作用。评估HPA轴的传统金标准——胰岛素低血糖试验（IHT）存在一些已知局限性，而另一种试验——标准促肾上腺皮质激素（ACTH）刺激试验，能够检测出严重的皮质醇缺乏，但常常遗漏轻度或早期病例。因此，需要一种更好的评估HPA轴的试验。本研究评估了阿片类拮抗剂纳美芬作为HPA轴刺激试验的效果。
对25名健康受试者进行研究，其中9名女性，16名男性，平均年龄30.4岁（范围21 - 55岁），平均体重指数（BMI）为24.1kg/m²（范围18.6 - 34.2）。受试者静脉注射3种剂量之一的纳美芬：2mg（n = 6）、6mg（n = 12）或10mg（n = 7）。在注射纳美芬前及注射后两小时内连续测量血清皮质醇和血浆ACTH水平。
10mg剂量和6mg剂量后，ACTH和皮质醇水平显著且相似地升高。10mg剂量后，平均ACTH峰值为82.4±22.6pg/ml，平均皮质醇峰值为25.2±1.8μg/dl。6mg剂量后，平均ACTH峰值为70.3±7.7pg/ml，平均皮质醇峰值为24.7±1.7μg/dl。所有接受10mg纳美芬的受试者以及除两名受试者外所有接受6mg纳美芬的受试者的皮质醇水平均升至18μg/dl以上。与接受6mg或2mg纳美芬的受试者相比，接受10mg纳美芬的受试者出现的纳美芬副作用持续时间更长、强度更大。这些副作用最显著的包括疲劳、头晕、恶心和呕吐。
在我们研究的纳美芬剂量中，6mg剂量在刺激ACTH和皮质醇方面达到了最佳组合，且副作用最少。如果进一步研究表明纳美芬与IHT结果一致，那么纳美芬试验可用于评估有HPA轴功能障碍风险患者的HPA轴。
