Effects of recombinant human growth hormone (GH) on bone and intermediary metabolism in patients receiving chronic glucocorticoid treatment with suppressed endogenous GH response to GH-releasing hormone.
Glucocorticoids, when administered over prolonged periods of time, cause protein wasting, osteoporosis, elevation of total cholesterol, and carbohydrate intolerance. Human GH is a potent anabolic agent known to stimulate protein synthesis and osteoblast activity. Chronic hypercortisolemia is associated with impaired GH secretion. The aim of our study was to evaluate the effects of short term administration of human recombinant GH on bone and fuel metabolism in patients receiving chronic glucocorticoid treatment and with suppressed GHRH-stimulated GH peaks (< 10 micrograms/L). We studied nine nonobese adult patients more than 70 yr of age (seven females and two males; age range, 41-68 yr; body mass index, 26 +/- 1.3 kg/m2) undergoing long term glucocorticoid therapy for nonendocrine diseases. After a 3-day stabilization period in the hospital, several parameters were evaluated in all patients: 1) protein, 2) bone, 3) lipid, 4) carbohydrate metabolism, and 5) immune system function under baseline conditions. At 1800 h on the fifth day of hospitalization, the patients began treatment with a daily sc injection of 0.1 IU/kg (0.037 mg/kg) recombinant human GH (Humatrope, Eli Lilly Co.) for 7 days. GH administration caused a significant increase in nitrogen balance (from -0.12 +/- 0.04 to -0.03 +/- 0.02 g/kg.day; P < 0.05), osteocalcin, carboxy-terminal propeptide of type I procollagen, and carboxy-terminal telopeptide of type I collagen with respect to basal levels. After GH administration, total, high density lipoprotein, and low density lipoprotein cholesterol levels were significantly lowered, and serum triglyceride levels were increased in all patients. Normal blood glucose levels during GH administration were observed in our patients concomitantly with a slight increase in insulin secretion. After GH treatment, the T-helper/T-suppressor cell ratio significantly increased with respect to basal levels (2.5 +/- 0.4 vs. 2.2 +/- 0.3; P < 0.05). Our data suggest that in patients receiving chronic glucocorticoid treatment, GH administration may significantly antagonize several side-effects of long term glucocorticoid administration, such as protein wasting, osteoporosis, and hyperlipidemia.
Giustina
A
A
Cattedra di Clinica Medica and Chimica, University of Brescia, Italy.
Bussi
A R
AR
Jacobello
C
C
Wehrenberg
W B
WB
D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism / Q000627:therapeutic use*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000503:physiopathology; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins; D013997:Time Factors
D005938:Glucocorticoids; D011506:Proteins; D011994:Recombinant Proteins; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D005947:Glucose