Neeck G, Crofford L J
Department of Rheumatology, University of Giessen, Bad Nauheim, Germany.
Rheum Dis Clin North Am. 2000 Nov;26(4):989-1002. doi: 10.1016/s0889-857x(05)70180-0.
A large body of data from a number of different laboratories worldwide has demonstrated a general tendency for reduced adrenocortical responsiveness in CFS. It is still not clear if this is secondary to CNS abnormalities leading to decreased activity of CRH- or AVP-producing hypothalamic neurons. Primary hypofunction of the CRH neurons has been described on the basis of genetic and environmental influences. Other pathways could secondarily influence HPA axis activity, however. For example, serotonergic and noradrenergic input acts to stimulate HPA axis activity. Deficient serotonergic activity in CFS has been suggested by some of the studies as reviewed here. In addition, hypofunction of sympathetic nervous system function has been described and could contribute to abnormalities of central components of the HPA axis. One could interpret the clinical trial of glucocorticoid replacement in patients with CFS as confirmation of adrenal insufficiency if one were convinced of a positive therapeutic effect. If patient symptoms were related to impaired activation of central components of the axis, replacing glucocorticoids would merely exacerbate symptoms caused by enhanced negative feedback. Further study of specific components of the HPA axis should ultimately clarify the reproducible abnormalities associated with a clinical picture of CFS. In contrast to CFS, the results of the different hormonal axes in FMS support the assumption that the distortion of the hormonal pattern observed can be attributed to hyperactivity of CRH neurons. This hyperactivity may be driven and sustained by stress exerted by chronic pain originating in the musculoskeletal system or by an alteration of the CNS mechanism of nociception. The elevated activity of CRH neurons also seems to cause alteration of the set point of other hormonal axes. In addition to its control of the adrenal hormones, CRH stimulates somatostatin secretion at the hypothalamic level, which, in turn, causes inhibition of growth hormone and thyroid-stimulating hormone at the pituitary level. The suppression of gonadal function may also be attributed to elevated CRH because of its ability to inhibit hypothalamic luteinizing hormone-releasing hormone release; however, a remote effect on the ovary by the inhibition of follicle-stimulating hormone-stimulated estrogen production must also be considered. Serotonin (5-HT) precursors such as tryptophan (5-HTP), drugs that release 5-HT, or drugs that act directly on 5-HT receptors stimulate the HPA axis, indicating a stimulatory effect of serotonergic input on HPA axis function. Hyperfunction of the HPA axis could also reflect an elevated serotonergic tonus in the CNS of FMS patients. The authors conclude that the observed pattern of hormonal deviations in patients with FMS is a CNS adjustment to chronic pain and stress, constitutes a specific entity of FMS, and is primarily evoked by activated CRH neurons.
来自全球多个不同实验室的大量数据表明，慢性疲劳综合征（CFS）患者普遍存在肾上腺皮质反应性降低的趋势。目前尚不清楚这是否继发于中枢神经系统异常，导致产生促肾上腺皮质激素释放激素（CRH）或血管加压素（AVP）的下丘脑神经元活性降低。基于遗传和环境影响，已有关于CRH神经元原发性功能减退的描述。然而，其他途径可能会继发影响下丘脑-垂体-肾上腺（HPA）轴的活性。例如，5-羟色胺能和去甲肾上腺素能输入可刺激HPA轴的活性。本文综述的一些研究表明，CFS患者存在5-羟色胺能活性不足。此外，已有关于交感神经系统功能减退的描述，这可能导致HPA轴中枢成分的异常。如果有人确信糖皮质激素替代疗法对CFS患者有积极的治疗效果，那么可以将其临床试验解释为肾上腺功能不全的证据。如果患者的症状与轴中枢成分激活受损有关，那么补充糖皮质激素只会加重由增强的负反馈引起的症状。对HPA轴特定成分的进一步研究最终应能阐明与CFS临床表现相关的可重复性异常。与CFS相反，纤维肌痛综合征（FMS）中不同激素轴的结果支持这样一种假设，即观察到的激素模式扭曲可归因于CRH神经元的过度活跃。这种过度活跃可能由肌肉骨骼系统慢性疼痛产生的压力或伤害感受的中枢神经系统机制改变所驱动和维持。CRH神经元活性升高似乎也会导致其他激素轴设定点的改变。除了控制肾上腺激素外，CRH在下丘脑水平刺激生长抑素分泌，进而在垂体水平抑制生长激素和促甲状腺激素。性腺功能的抑制也可能归因于CRH升高，因为它能够抑制下丘脑促黄体生成素释放激素的释放；然而，也必须考虑通过抑制促卵泡激素刺激的雌激素产生对卵巢产生的间接影响。5-羟色胺（5-HT）前体，如色氨酸（5-HTP）、释放5-HT的药物或直接作用于5-HT受体的药物可刺激HPA轴，表明5-羟色胺能输入对HPA轴功能有刺激作用。HPA轴功能亢进也可能反映了FMS患者中枢神经系统中5-羟色胺能张力升高。作者得出结论，FMS患者观察到的激素偏差模式是中枢神经系统对慢性疼痛和压力的一种调整，构成了FMS的一个特定实体，主要由激活的CRH神经元引起。
