Different effects of continuous and intermittent patterns of growth hormone administration on lipoprotein levels in growth hormone-deficient patients.
BACKGROUND
Lipoprotein (a) (Lp(a)) is a risk marker for the development of atherosclerotic coronary heart disease. Growth hormone (GH) administration to GH-deficient (GHD) adults increases serum Lp(a) concentrations, and the levels of Lp(a) and GH are correlated in patients with acromegaly. Studies in rats have demonstrated differential effects of constant and intermittent GH patterns on levels of certain lipoproteins. The aim of the present studies was to describe the impact of intermittent and continuous patterns of GH delivery to GHD patients on serum levels of Lp(a) and other lipoproteins.


METHODS
In one study (A) 10 GHD patients received in random order a fixed GH dose intravenously as: (1) continuous infusion; (2) eight bolus injections, and (3) a combination of 1 and 2. Each study lasted 36 h and was preceded by at least 4 weeks without GH. In another study (B) 13 GHD patients received GH in random order as: (1) continuous subcutaneous (s.c.) infusion, and (2) daily s.c. injections in the evening for 1 month each. The patients were studied during steady-state conditions at the end of each treatment period.


RESULTS
In study A Lp(a) levels increased significantly following continuous (p < 0.05) and combined patterns (p < 0.02) of GH administration to GH-deprived GHD patients, whereas the increase after GH bolus injections alone was not significant (p = 0.14). In study B significantly higher (p < 0.05) serum levels of Lp(a) were obtained after continuous s.c. infusion as compared with daily s.c. injections of GH. Concentrations of the high-density lipoprotein (HDL) cholesterol were significantly lower (p < 0.02) after the continuous GH pattern. Similarly, the HDL fraction Apo A-1 tended to be lower with constant GH delivery (p = 0. 052). Serum levels of total cholesterol, triglyceride and Apo B were similar on the two occasions.


CONCLUSIONS
Short-term GH administration to GH-deprived GHD patients increased serum Lp(a), but only significantly with continuous delivery. During more prolonged GH exposure, constant s.c. infusion of GH resulted in slightly raised Lp(a) levels and reduced HDL and Apo A1 levels as compared with intermittently administered GH. The findings are consistent with the more effective induction of serum IGF-I levels after continuous patterns of GH delivery previously reported in GHD patients. Longer-term data are needed before conclusions with respect to the impact of the pattern of GH administration on, e.g., the risk of developing coronary heart disease can be drawn.
Laursen
T
T
Medical Department M (Endocrinology), Aarhus University Hospital, Kommunehospitalet and Centre for Clinical Pharmacology, Aarhus University, Denmark.
Lemming
L
L
Jørgensen
J O
JO
Klausen
I C
IC
Christiansen
J S
JS
D000293:Adolescent; D000328:Adult; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects* / Q000172:deficiency*; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017270:Lipoprotein(a); D019382:Human Growth Hormone; D002784:Cholesterol