The effects of GH replacement therapy on cardiac morphology and function, exercise capacity and serum lipids in elderly patients with GH deficiency.
OBJECTIVE
To assess effects of GH replacement therapy on cardiac structure and function, exercise capacity as well as serum lipids in elderly patients with GH deficiency (GHD).


METHODS
Thirty-one patients (six females, 25 males), aged 60-79 years (mean 68 years) with GHD on stable cortisone and thyroxine substitution were studied. All men with gonadotropin deficiency had testosterone and one woman had oestrogen replacement. They were randomized in a double-blind manner to GH or placebo treatment for 6 months, followed by another 12 months GH (Humatrope, Eli Lilly & Co, Uppsala, Sweden). GH dose was 0.017 mg/kg/week for 1 month and then 0.033 mg/kg/week divided into daily subcutaneous injections at bedtime. Echocardiography, exercise capacity tests and serum lipid measurements were performed at 0, 6, 12 and 18 months.


RESULTS
During the 6-month placebo-controlled period there were no significant changes in the placebo group, but in the GH-treated group there was a significant increase in IGF-I to normal levels for age, with median IGF-I from 6.9 to 18.5 nmol/l, increase in resting heart rate and maximal working capacity. During the open GH study, IGF-I increased from 8.7 to 19.2 nmol/l at 6 months and 18.8 nmol/l at 12 months (P </= 0.001). At 6 months, in the open GH study group, a minor decrease in aortic outflow tract integral (VTI) from 21.8 to 20.7 cm (P = 0.031) and an increase in heart rate at rest from 63 to 67 bpm (P = 0.017), heart rate at maximum exercise from 138 to 144 bpm (P = 0.005) and maximum load at exercise from 142 to 151 Watts (P = 0.014) were seen. These changes were temporary and returned at 12 months with no significant difference from baseline values. Left ventricular dimensions and blood pressure showed no significant changes. At 6 months, in the open GH study group, there was a significant decrease in serum low-density lipoprotein (LDL) cholesterol from 3.7 to 3.4 mmol/l (P = 0.006), a decrease in LDL/HDL ratio from 3.4 to 3.1 (P = 0.036) and a decrease in serum total cholesterol from 5.6 to 5.3 mmol/l (P = 0.036). At 12 months, serum lipids showed same changes with a significant decrease in serum LDL cholesterol (P = 0.0008), in LDL/HDL ratio (P = 0.0005) and in serum total cholesterol (P = 0.049). Serum HDL cholesterol showed no significant change at 6 months, at 12 months a significant increase was seen from 1.2 to 1.4 mmol/l (P = 0.007). There were no significant changes in serum triglycerides.


CONCLUSIONS
GH substitution to elderly patients with GHD caused only a transient increase in heart rate. At the end of the 12 months there were no significant changes on cardiac noninvasive structural and functional parameters. Maximal working capacity transiently improved. Thus, the therapy was safe without negative effects on cardiac structural and functional noninvasive parameters. Lipid profiles improved with reduction of serum LDL cholesterol accompanied by significant improvement of LDL/HDL ratio and serum HDL cholesterol after 12 months treatment.
Elgzyri
Targ
T
Department of Endocrinology, University Hospital, Malmo, Sweden. targ.elgzyri@skane.se
Castenfors
Jan
J
Hägg
Erik
E
Backman
Christer
C
Thorén
Marja
M
Bramnert
Margareta
M
D000368:Aged; D002784:Cholesterol / Q000097:blood; D003348:Cortisone / Q000627:therapeutic use; D004311:Double-Blind Method; D004452:Echocardiography; D015914:Estrogen Replacement Therapy; D017079:Exercise Tolerance; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D020249:Hormone Replacement Therapy; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000008:administration & dosage; D013974:Thyroxine / Q000627:therapeutic use
D008055:Lipids; D011994:Recombinant Proteins; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D002784:Cholesterol; D013974:Thyroxine; D003348:Cortisone