Ramirez G, Bittle P A, Sanders H, Rabb H A, Bercu B B
Department of Internal Medicine, James A. Haley Veterans' Administration Hospital, Tampa, Florida 33612.
J Clin Endocrinol Metab. 1994 Jan;78(1):63-9. doi: 10.1210/jcem.78.1.8288716.
Endocrine abnormalities in chronic hemodialysis patients are in part corrected by control of anemia with recombinant human erythropoietin (rHu-EPO). We further examined the role of rHu-EPO in select hormonal abnormalities thought to be anemia related as well as the GH-insulin-like growth factor 1 (GH-IGF-1) axis that is abnormal in hemodialysis patients. We studied responses to the administration of two hypothalamic hormones, GHRH and ovine corticotropin-releasing hormone (CRH), in five anemic male patients on chronic hemodialysis before and after correction of the anemia with rHu-EPO. For comparison, five age-matched normal male volunteers were tested once. Anemic patients on chronic hemodialysis had high basal GH concentrations, an exaggerated GH response to exogenous GHRH, increased levels of IGF-1, and elevated levels of IGF-1 binding protein-3 in comparison to controls. ACTH response to CRH was comparable in dialysis patients and normal controls, but the cortisol response to endogenous ACTH release was prolonged. The cortisol binding globulin was similar to the controls. After correction of anemia, the basal elevation of GH was no longer present, but the exaggerated response of GH to exogenous GHRH persisted. IGF-1 and IGF-1 binding protein-3 levels remained elevated. The ACTH response to CRH, which was normal before correction of the anemia, became exaggerated in terms of elevated levels. Nevertheless, the prolonged cortisol response persisted. It appears that correction of the anemia in hemodialysis patients with rHu-EPO can partly correct perturbations in the GH secretory axis but may lead to new abnormalities in the CRH-ACTH axis.
慢性血液透析患者的内分泌异常部分可通过使用重组人促红细胞生成素(rHu-EPO)控制贫血来纠正。我们进一步研究了rHu-EPO在某些被认为与贫血相关的激素异常以及血液透析患者中异常的生长激素-胰岛素样生长因子1(GH-IGF-1)轴中的作用。我们研究了5名接受慢性血液透析的贫血男性患者在用rHu-EPO纠正贫血前后,对两种下丘脑激素促生长激素释放激素(GHRH)和羊促肾上腺皮质激素释放激素(CRH)给药的反应。作为对照,对5名年龄匹配的正常男性志愿者进行了一次测试。与对照组相比,接受慢性血液透析的贫血患者基础生长激素浓度较高,对外源性GHRH的生长激素反应过度,胰岛素样生长因子1水平升高,胰岛素样生长因子1结合蛋白-3水平升高。透析患者对CRH的促肾上腺皮质激素(ACTH)反应与正常对照组相当,但皮质醇对内源性ACTH释放的反应延长。皮质醇结合球蛋白与对照组相似。贫血纠正后,生长激素的基础升高不再存在,但生长激素对外源性GHRH的过度反应仍然存在。胰岛素样生长因子1和胰岛素样生长因子1结合蛋白-3水平仍升高。贫血纠正前正常的对CRH的ACTH反应,在水平升高方面变得过度。然而,皮质醇反应延长仍然存在。看来,用rHu-EPO纠正血液透析患者的贫血可以部分纠正GH分泌轴的紊乱,但可能导致CRH-ACTH轴出现新的异常。