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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B); group A (n = 17) received appropriate replacement therapy including GH at standard doses for 6 months and then were withdrawn from GH for the subsequent 6 months; group B (n = 17) received appropriate replacement therapy excluding GH for 6 months with the addition of GH in the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.

In 100 patients with hypopituitarism and 80 sex- and age-matched healthy subjects, we correlated the severity of cardiac impairment to the severity of GH deficiency (GHD). By the GH peak after arginine plus GHRH test (normal > 16.5 microg/liter), the patients were classified as severe GHD (n = 56), partial GHD (n = 27), and non-GHD (n = 17). Compared with controls, decreased left ventricular ejection fraction at rest was found only in severe GHD patients (55.0 +/- 8.8 vs. 63.4 +/- 4.5%, P < 0.001); decreased left ventricular ejection fraction response on effort in severe (-4.6 +/- 17.4 vs. 15.2 +/- 9.1%, P < 0.001) and partial GHD patients (3.6 +/- 6.6 vs. 14.6 +/- 8.3%, P < 0.001); decreased diastolic filling at rest in severe (2.53 +/- 0.68 vs. 3.01 +/- 0.48 end-diastolic volume per second, P < 0.001) and partial GHD (2.61 +/- 0.45 vs. 2.89 +/- 0.54 end-diastolic volume per second, P = 0.004) patients; and decreased exercise duration and capacity in all the patient groups. A normal systolic performance on effort was found in 21.4% of severe GHD, 55.6% of partial GHD, all non-GHD, and 93.7% of controls. A normal diastolic filling at rest was found in 57.1% of severe GHD, 74.1% of partial GHD, 76.5% of non-GHD, and 90% of controls. In conclusion, cardiac performance is correlated with the GH status because significant impairment was found in patients with severe and partial GHD but not in non-GHD hypopituitary patients.