Growth Hormone Treatment Improves Serum Lipids and Lipoproteins in Adults With Growth Hormone Deficiency R. C. CUNEO, F. SALOMON, G. F. WATTS, ET AL Metabolism 42:1519–1523, 1993

Previous studies suggest that growth hormone (GH) deficiency is associated with an increased risk of cardiovascular morbidity and mortality. 1 Several studies have demonstrated hypercholesterolemia and hypertriglyceridemia in both children and adults with GH deficiency. 2 However, the effects of GH replacement therapy on serum lipids in GH‐deficient children have been inconsistent, and no previous prospective studies on the effects of GH on lipoprotein metabolism in GH‐deficient adults have been reported. In this study, the authors describe the effects of 6 months of physiologic GH replacement therapy on serum lipids and lipoproteins in 24 adults with GH deficiency. The effects of GH replacement on body composition and metabolism were previously reported in these individuals. 3 In that report, GH improved indices of lean body mass and diminished fat mass during a 6‐month period; the current study extends the previous finding of decreased serum cholesterol levels during GH treatment. 3 Patients (aged 18 to 52 years) with documented GH deficiency secondary to pituitary surgery or irradiation comprised the study group. The patients were receiving conventional and stable doses of pituitary hormone replacement therapy as required (glucocorticoids, thyroxine, and sex steroids). Those with underlying diseases or those taking drugs known to affect lipid metabolism were excluded. Sex‐ and age‐matched healthy control subjects were also studied. The patients received recombinant GH (0.07 U/kg·day −1 or = 0.025 mg/kg·day −1 , subcutaneously) or subcutaneous saline placebo daily for 6 months in a double‐blind manner. The two groups of patients were matched for age, sex, height, and weight at entry. Venous blood was taken at 9 AM after an overnight fast before treatment and after 1, 3, and 6 months of treatment, and the lipid and lipoprotein concentrations were analyzed. Results are expressed as mean ± SEM. Compared with non‐GH‐deficient healthy controls, GH‐deficient subjects exhibited significant abnormalities in several circulating lipoproteins before treatment. GH‐deficient patients had higher serum levels of total cholesterol (control 4.89 ± 0.17 mmol/L vs GH deficient 5.85 ± 0.22; p =.02), triglycerides (1.24 ± 0.09 mmol/L vs 2.18 ± 1.24; p =.017), low‐density lipoprotein (LDL) cholesterol (3.06 ± 0.16 mmol/L vs 4.10 ± 0.20; p <.001), and apolipoprotein B (apo B) (0.84 ± 0.04 g/L vs 1.01 ± 0.05; p =.011), and significantly lower levels of serum high‐density lipoprotein (HDL) cholesterol (control 1.26 ± 0.06 mmol/L vs GH deficient 0.83 ± 0.06; p <.001). The percentage of patients with elevated serum lipids or lipoproteins more than two standard deviations from the control mean was 39% for total cholesterol, 26% for triglycerides, 39% for LDL cholesterol, 25% for apo B, and 70% for the LDL to HDL cholesterol ratio. In the randomized portion of the study, GH treatment significantly decreased serum cholesterol levels (by 12%) compared with placebo treatment (by repeated measures analysis of variance), decreased LDL cholesterol by 32%, and decreased apo B levels by 37%. HDL cholesterol levels tended to rise with GH (not significant), and the LDL to HDL ratio fell significantly (from 5.57 ± 0.47 at entry to 3.29 ± 0.33 in GH‐treated patients vs no change in placebo controls). No significant change in free fatty acids or triglycerides occurred with GH over time. The alterations in lipid and lipoprotein levels were not significantly correlated with insulin, insulin‐like growth factor‐I, glucagon, thyroid hormone levels, or indices of adiposity (fat mass, multiple skin‐fold measurements).