The effect of growth hormone replacement on serum lipids, lipoproteins, apolipoproteins and cholesterol precursors in adult growth hormone deficient patients.
OBJECTIVE
Adult patients with growth hormone deficiency are thought to be at higher risk of mortality from cardiovascular disease. We therefore investigated the effect of recombinant human growth hormone (rhGH) replacement therapy on fasting serum concentrations of lipids, lipoproteins and cholesterol precursors in adult growth hormone deficient patients.


METHODS
Double-blind placebo controlled trial. Patients were randomly allocated to placebo or rhGH replacement therapy (0.018 U/kg/day for 1 month followed by 0.036 U/kg/day for 1 month).


METHODS
Eighteen patients with severe growth hormone deficiency.


METHODS
Fasting lipid, lipoprotein and cholesterol precursors (lathosterol and mevalonic acid) were measured at baseline and after 2 months.


RESULTS
In the rhGH treated group there was a significant fall in serum cholesterol (P < 0.01) (6.44 +/- 0.49 to 5.71 +/- 0.48 mmol/l), LDL cholesterol (P < 0.02) (4.29 +/- 0.49 to 3.62 +/- 0.44 mmol/l), LDL cholesterol/HDL cholesterol ratio (P < 0.02) (3.99 +/- 0.62 to 3.26 +/- 0.39), apolipoprotein B (P < 0.01 (1.30 +/- 0.11 to 1.15 +/- 0.11 g/l) and mevalonic acid (P < 0.05) (13.4 +/- 10.96 to 6.21 +/- 1.91 micrograms/l). There were no significant changes in triglycerides, HDL cholesterol, apolipoprotein A1, lipoprotein (a) or lathosterol concentrations. In the GH treated group the rise in serum insulin was inversely correlated with the fall in cholesterol (P < 0.05), LDL cholesterol (P < 0.01) and apolipoprotein B (P < 0.01). There were no significant changes in any of the measured variables in the placebo group.


CONCLUSIONS
We conclude that GH may be involved in the regulation of lipid and lipoprotein metabolism and that rhGH replacement therapy of adult GHD patients is associated with beneficial changes in lipid and lipoprotein profiles. The reduction in mevalonic acid is consistent with up-regulation of hepatic LDL receptors caused by GH and this may explain the fall in LDL cholesterol and apolipoprotein B concentrations.
Department of Endocrinology and Chemical Pathology, UMDS, St Thomas' Campus, London, UK.
D L
DL
Russell-Jones
G F
GF
Watts
A
A
Weissberger
R
R
Naoumova
J
J
Myers
G R
GR
Thompson
P H
PH
Sönksen
D000328:Adult; D001053:Apolipoproteins / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy*; D013006:Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008798:Mevalonic Acid / Q000097:blood; D008875:Middle Aged
D001053:Apolipoproteins; D008055:Lipids; D008074:Lipoproteins; C001521:lathosterol; D013006:Growth Hormone; D002784:Cholesterol; D008798:Mevalonic Acid