Hochberg Ze'ev, Pacak Karel, Chrousos George P
Division of Endocrinology (Z.H.), Meyer Children's Hospital, Haifa 31096, Israel.
Endocr Rev. 2003 Aug;24(4):523-38. doi: 10.1210/er.2001-0014.
Hypersecretion of endogenous hormones or chronic administration of high doses of the same hormones induces varying degrees of tolerance and dependence. Elimination of hormone hypersecretion or discontinuation of hormone therapy may result in a mixed picture of two syndromes: a typical hormone deficiency syndrome and a generic withdrawal syndrome. Thus, hormones with completely different physiological effects may produce similar withdrawal syndromes, with symptoms and signs reminiscent of those observed with drugs of abuse, suggesting shared mechanisms. This review postulates a unified endocrine withdrawal syndrome, with changes in the hypothalamic-pituitary-adrenal axis and the central opioid peptide, in which noradrenergic and dopaminergic systems of the brain act as common links in its pathogenesis. Long-term adaptations to hormones may involve relatively persistent changes in molecular switches, including common intracellular signaling systems, from membrane receptors to transcription factors. The goals of therapy are to ease withdrawal symptoms and to expedite weaning of the patient from the hormonal excess state. Clinicians should resort to the fundamentals of tapering hormones down over time, even in the case of abrupt removal of a hormone-producing tumor. In addition, the prevention of stress and concurrent administration of antidepressants may ameliorate symptoms and signs of an endocrine withdrawal syndrome.
内源性激素分泌过多或长期大剂量使用相同激素会导致不同程度的耐受性和依赖性。消除激素分泌过多或停止激素治疗可能会导致两种综合征的混合表现:典型的激素缺乏综合征和一般的戒断综合征。因此,具有完全不同生理作用的激素可能会产生相似的戒断综合征,其症状和体征让人联想到滥用药物时观察到的症状和体征,这表明存在共同机制。本综述提出了一种统一的内分泌戒断综合征,涉及下丘脑 - 垂体 - 肾上腺轴和中枢阿片肽的变化,其中大脑中的去甲肾上腺素能和多巴胺能系统在其发病机制中起共同作用。对激素的长期适应可能涉及分子开关的相对持久变化,包括从膜受体到转录因子的常见细胞内信号系统。治疗的目标是缓解戒断症状并加快患者从激素过量状态中撤药。临床医生应采用随着时间逐渐减少激素剂量的基本原则,即使在突然切除产生激素的肿瘤的情况下也是如此。此外,预防应激和同时使用抗抑郁药可能会改善内分泌戒断综合征的症状和体征。