Increased lipid peroxidation in adult GH-deficient patients: effects of short-term GH administration.
OBJECTIVE
Adult GH deficiency (GHD) syndrome is characterized by increased risk of atherosclerosis and hence of cardio- and cerebrovascular mortality. Oxidative stress appears to play an important role in early atherogenesis. Oxidized LDL represents an important predictor of cardiovascular risk and is mainly responsible for oxidative damage of the endothelium. Its concentrations are increased in GHD, but the association between this abnormality and oxidative stress is still unclear, due to the discordant results yielded by the few available studies.


METHODS
In 13 GHD patients, plasma lipid peroxide concentrations were measured before and after a 4-month treatment with recombinant human GH (rhGH) and compared with those of 13 age- and sex-matched controls. In the same subjects, the so-called "lag-time", an index of anti-oxidant activity and thus of plasma oxidative balance, was also measured using a fluorescence kinetics method.


RESULTS
Before treatment, peroxide levels were significantly higher in patients than in controls (374.0+/-31.52 vs 268.0+/-8.51 U.C., p<0.01), whereas the lag-time was significantly lower (113.0+/-10.70 vs 168.0+/-7.80 min, p<0.01). RhGH administration to patients resulted both in a significant decrease in lipid peroxide levels (from 374.0+/-31.52 to 336.0+/-33.17 U.C., p<0.01) and a significant prolongation of lag-time (from 113.0+/-10.70 to 144.0+/-15.00 min, p<0.01). After treatment, both parameters were no longer significantly different in patients and controls. Lag-time and peroxide levels at baseline did not show any correlation with IGF-I concentrations in GHD patients. After replacement therapy, however, lag-time was positively (r2= 0.62, p<0.01), and peroxide levels negatively (r2=0.41, p<0.05), correlated with IGF-I levels.


CONCLUSIONS
These data support the view that adult GHD syndrome is characterized by an unbalance between pro- and anti-oxidant factors with marked preponderance of the former. This abnormality, likely contributing to the increased atherogenic risk of GHD patients, is corrected by short-term GH administration at a dose able to increase, although not to fully normalize, IGF-I levels.
Scacchi
M
M
University of Milan, Ospedale San Luca IRCCS, Istituto Auxologico Italiano, Milan, Italy.
Valassi
E
E
Pincelli
A I
AI
Fatti
L M
LM
Pecori Giraldi
F
F
Ascoli
P
P
Viarengo
R
R
Cestaro
B
B
Cavagnini
F
F
Cazzola
R
R
D000328:Adult; D050197:Atherosclerosis / Q000209:etiology / Q000503:physiopathology; D016022:Case-Control Studies; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008054:Lipid Peroxides / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D012307:Risk Factors; D013577:Syndrome; D013997:Time Factors
D008054:Lipid Peroxides; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone