Low-dose GH replacement improves the adverse lipid profile associated with the adult GH deficiency syndrome.
OBJECTIVE
Adult growth hormone deficiency (AGHD) is associated with an adverse lipid profile. The majority of previous studies of GH replacement have used supraphysiological doses and reported favourable changes in the lipid profile. Whether this beneficial effect is the result of pharmacological GH therapy, or occurs in response to low-dose GH replacement aimed at normalization of the serum IGF-I, has not been fully elucidated.


METHODS
We studied 67 patients with GH deficiency using a low-dose individualized GH replacement regimen. GH was commenced at a dose of 0.27 mg/day and the GH dose titrated until the serum IGF-I was normalized. Serum lipids were assessed at baseline, 12 and 24 months.


RESULTS
A reduction in total cholesterol (TC) was observed at 12 (6.01 vs. 5.77 mmol, P = 0.04) and 24 months (6.01 vs. 5.56, P = 0.09). The reduction in LDLC failed to reach significance at 12 months (3.97 vs. 3.8, P = 0.09), but was significant at 24 months (3.97 vs. 3.50, P = 0.02). Levels of HDLC did not change significantly at 12 or 24 months. Significant improvements in the TC/HDLC ratio were observed at both 12 (5.68 vs. 5.29, P = 0.01) and 24 months (5.68 vs. 4.86, P = 0.007). A significant fall in triglycerides (TG) was present at 12 months (2.07 vs. 1.83, P = 0.01), and was maintained at 24 months, but was no longer significant (2.07 vs. 1.89, P = 0.28). At 12 months there was no correlation between improvements in lipid parameters and either the change in IGF-I SD score or the GH dose. Using multivariate analysis the change in TC, LDLC and the TC/HDLC ratio with 12 months GH replacement were determined by the baseline TC, LDLC and TC/HDLC levels (R2 = 0.18, P = 0.004; R2 = 0.20, P = 0.006; and R2 = 0.33, P < 0.0001), respectively.


CONCLUSIONS
Low-dose individualized GH replacement aimed at normalization of the serum IGF-I is associated with significant improvements in TC, LDLC, TGs and the TC/HDLC ratio. The greatest improvements are observed in patients with the most adverse lipid profiles at baseline. Improvements are independent of changes in the IGF-I SDS and GH dose.
Murray
R D
RD
Department of Endocrinology, The Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
Wieringa
G E
GE
Lissett
C A
CA
Darzy
K H
KH
Smethurst
L E
LE
Shalet
S M
SM
D000328:Adult; D001823:Body Composition / Q000187:drug effects; D002648:Child; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D014280:Triglycerides; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol