Dose-, IGF-I- and sex-dependent changes in lipid profile and body composition during GH replacement therapy in adult onset GH deficiency.
OBJECTIVE
Patients with GH deficiency of adult onset (GHDA) exhibit dyslipidaemia and increased cardiovascular morbidity. GH replacement potently reduces body fat and serum lipids in GHDA. In recent years, lower GH doses have been introduced. The purpose of this analysis was to explore the response relationship between GH doses, lipids and body composition.


METHODS
Two consecutive, randomized 12-month GH replacement studies covering placebo and three different doses of GH (0.5, 1.0 and 1.7 IU/m(2) per day). Low and intermediate doses were IGF-I titrated.


METHODS
Fifty-eight patients with severe GHDA, not previously treated with GH and stably substituted for other endocrine deficiencies, were included in the study.


METHODS
Serum lipoproteins, serum IGF-I and body composition analysis by dual energy X-ray absorptiometry (DXA) were used.


RESULTS
Fifty-seven percent of patients exhibited low density lipoprotein (LDL) cholesterol levels above 4.16 mmol/l, corresponding to the American Heart Association threshold of 160 mg/dl. GH treatment resulted in significant decreases in total and LDL cholesterol, with no significant change in high density lipoprotein cholesterol or triglycerides. The low dose induced no significant changes in lipid levels, whereas the medium dose reduced LDL cholesterol and the high dose decreased both LDL and total cholesterol. The effects depended significantly on the GH dose and the level of IGF-I obtained, but not on gender. GH replacement induced dose-dependent reductions in fat mass and sex-dependent increases in lean mass.


CONCLUSIONS
GH given for 1 year at a dosage between 0.5 and 1.7 IU/m(2) per day reduced fat mass in a dose-dependent manner, increased lean body mass and lowered total and LDL cholesterol in patients with severe GHDA. Low dose GH treatment with normal IGF-I levels induced smaller changes compared with high dose therapy, and may need a longer treatment time.
Abrahamsen
B
B
Department of Endocrinology M, Odense University Hospital, Odense, Denmark.
Nielsen
T L
TL
Hangaard
J
J
Gregersen
G
G
Vahl
N
N
Korsholm
L
L
Hansen
T B
TB
Andersen
M
M
Hagen
C
C
D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000328:Adult; D017668:Age of Onset; D001823:Body Composition; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage* / Q000009:adverse effects / Q000172:deficiency*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D012720:Severity of Illness Index; D012727:Sex Characteristics; D013851:Thinness
D008078:Cholesterol, LDL; D008055:Lipids; D008074:Lipoproteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone