Short-Term Effects of Growth Hormone (GH) Treatment or Deprivation on Cardiovascular Risk Parameters and Intima-Media Thickness at Carotid Arteries in Patients with Severe GH Deficiency

To explore early effects of GH treatment or deprivation on cardiovascular risk factors and carotid intima-media thickness (IMT), we designed this randomized, cross-over study in 34 adult patients with severe GH deficiency. At study entry, the patients were randomized into two groups (A and B); group A (n = 17) received appropriate replacement therapy including GH at standard doses for 6 months and then were withdrawn from GH for the subsequent 6 months; group B (n = 17) received appropriate replacement therapy excluding GH for 6 months with the addition of GH in the subsequent 6 months. After the first 6 months, we observed a significant increase in IGF-I levels and of high-density lipoprotein (HDL)-cholesterol together with a significant decrease in diastolic blood pressure, the total/HDL-cholesterol ratio, and C-reactive protein in the patients in group A, whereas vascular parameters did not significantly change. In the patients in group B, none of the parameters studied significantly changed. After 6 months of GH withdrawal in the patients in group A, a significant decrease in IGF-I levels, a significant increase in the total/HDL-cholesterol ratio and C-reactive protein, and a trend toward an impairment of carotid IMT and peak velocities were observed. In the patients in group B, the addition of GH to the standard replacement induced a significant increase in IGF-I levels together with a decrease in systolic and diastolic blood pressure, total cholesterol and total/HDL-cholesterol ratio, and C-reactive protein, and an increase in HDL-cholesterol levels with a trend toward an improvement of vascular parameters. At the end of the study, mean IMT was significantly lower than at baseline both in group A (from 0.88 +/- 0.28 to 0.85 +/- 0.27 mm, P = 0.0003) and in group B (from 0.83 +/- 0.21 to 0.80 +/- 0.20 mm, P = 0.003). In conclusion, 6 months of GH replacement has beneficial effects whereas 6 months of GH deprivation has detrimental effects on cardiovascular risk factors and atherosclerosis. These findings support the indication for GH replacement in severe GH deficiency adult patients.