The effects of corticotropin and growth hormone releasing hormones on their respective secretory axes in chronic hemodialysis patients before and after correction of anemia with recombinant human erythropoietin.
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.
Ramirez
G
G
Department of Internal Medicine, James A. Haley Veterans' Administration Hospital, Tampa, Florida 33612.
Bittle
P A
PA
Sanders
H
H
Rabb
H A
HA
Bercu
B B
BB
D000328:Adult; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004921:Erythropoietin / Q000627:therapeutic use*; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009747:Nutritional Physiological Phenomena; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011994:Recombinant Proteins; D006435:Renal Dialysis; D012756:Sheep; D013997:Time Factors
D011994:Recombinant Proteins; D004921:Erythropoietin; D013006:Growth Hormone; D003346:Corticotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone; D006854:Hydrocortisone