Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 1: Adrenocortical and pituitary glucocorticoid responsiveness
Dissection of hypothalamic-pituitary-adrenal axis pathology in 1-month-abstinent alcohol-dependent men, part 1: Adrenocortical and pituitary glucocorticoid responsiveness
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DOI：
10.1097/01.alc.0000158940.05529.0a
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发表时间：
2005-04-01
期刊：
影响因子：
--
通讯作者：
Williams, MJ
中科院分区：
文献类型：
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作者：
Adinoff, B;Krebaum, SR;Williams, MJ
背景：长期摄入酒精可显著改变下丘脑-垂体-肾上腺轴的活性。作者进行了一系列研究，以确定下丘脑、垂体和肾上腺在戒断酒精依赖受试者中观察到的紊乱中所起的独特作用。在这个两部分研究的第一部分中，作者报告了(1)从2000到0800小时促肾上腺皮质激素和皮质醇的基础分泌谱，(2)存在和不存在内源性垂体激活的肾上腺皮质敏感性，以及(3)垂体糖皮质激素对地塞米松的敏感性。方法：对11名戒酒4 ~ 6周的男性酒精依赖者和10名年龄匹配的男性健康对照者进行研究。从2000至0800小时获得促肾上腺皮质激素和皮质醇的基础循环浓度。然后给予次最大剂量的促肾上腺皮质激素类似物共syntropin (0.01 μ g/kg)，以评估肾上腺皮质敏感性。在一个单独的疗程中，在高剂量地塞米松（8mg iv）后给予共syntropin，以评估内源性促肾上腺皮质激素相对缺乏时肾上腺皮质的敏感性。此外，测量促肾上腺皮质激素对地塞米松的反应，以确定垂体糖皮质激素的反应。结果：酒精依赖组皮质醇、脉搏幅值（p < 0.05）和平均浓度（p = 0.05）明显低于对照组，促肾上腺皮质激素无明显差异。高剂量地塞米松抑制内源性促肾上腺皮质激素后，酒精依赖受试者对共syntropin的皮质醇反应较低（p < 0.04），但未进行地塞米松预处理的受试者对共syntropin的皮质醇反应较低。与对照组相比，患者对地塞米松反应的平均促肾上腺皮质激素（p < 0.004）和皮质醇（p < 0.05）浓度降低。11-脱氧皮质醇（皮质醇的前体）的基础浓度也在酒精依赖的受试者中降低（p < 0.05）。结论：在戒酒的酒精依赖男性中，基底和刺激肾上腺皮质浓度的减弱伴随着垂体糖皮质激素抑制的非稳态增加。酒精依赖中应激轴反应的降低可能对治疗结果有影响。
Background: Long-term ingestion of alcohol produces marked alterations in hypothalamic-pituitary-adrenal axis activity. The authors engaged in a series of studies to determine the distinct role of the hypothalamus and the pituitary and adrenal glands in the disturbances observed in abstinent alcohol-dependent subjects. In this first of a two-part study, the authors report on (1) the basal secretory profile of corticotropin and cortisol from 2000 to 0800 hrs, (2) adrenocortical sensitivity in both the presence and absence of endogenous pituitary activation, and (3) pituitary glucocorticoid sensitivity to dexamethasone.Methods: Eleven male, 4 to 6 weeks abstinent, alcohol-only-dependent subjects and 10 age-matched male healthy controls were studied. Basal circulating concentrations of corticotropin and cortisol were obtained from 2000 to 0800 hr. A submaximal dose of cosyntropin (0.01 mu g/kg), a corticotropin analogue was then administered to assess adrenocortical sensitivity. In a separate session, cosyntropin was administered following high-dose dexamethasone (8 mg iv) to assess adrenocortical sensitivity in the relative absence of endogenous corticotropin. In addition, the corticotropin response to dexamethasone was measured to determine pituitary glucocorticoid responsiveness.Results: Cortisol, but not corticotropin, pulse amplitude (p < 0.05) and mean concentration (p = 0.05) was significantly lower in alcohol-dependent subjects compared with controls. The cortisol response to cosyntropin was lower in alcohol-dependent subjects following endogenous corticotropin suppression by high-dose dexamethasone (p < 0.04) but not without dexamethasone pretreatment. Mean corticotropin (p < 0.004) and cortisol (p < 0.05) concentrations in response to dexamethasone were attenuated in the patients compared to controls. Basal concentrations of 11-deoxycortisol, the precursor to cortisol, were also decreased in alcohol-dependent subjects (p < 0.05).Conclusion: Attenuated basal and stimulated adrenocortical concentrations in abstinent alcohol-dependent men are coupled with a nonhomeostatic increase in pituitary glucocorticoid inhibition. A decrease in stress-axis responsivity in alcohol dependence may have implications for treatment outcome.