Effects of growth hormone treatment on arginine to asymmetric dimethylarginine ratio and endothelial function in patients with growth hormone deficiency.

Patients with growth hormone deficiency (GHD) are known to have reduced life expectancy due to increased cardiovascular and cerebrovascular events. An increase in asymmetric dimethylarginine (ADMA) levels previously found in GHD patients could promote premature atherosclerosis. The aim of this study was to determine whether 6-month growth hormone (GH) replacement therapy was able to decrease ADMA levels and ameliorate endothelial dysfunction. Thirty-one GHD patients were studied before and after 6 months of GH (4 microg/[kg d], daily) replacement therapy. Reduced pretreatment levels of serum insulin-like growth factor (IGF) 1 were normalized during GH treatment (88.2 +/- 62.5 to 191.7 +/- 80.3 ng/mL, P < .0001). After 6 months of GH replacement, plasma cyclic guanosine monophosphate levels significantly increased (2.14 +/- 0.52 to 3.54 +/- 1.2 ng/mL, P < .0001), serum ADMA levels were significantly decreased (0.65 +/- 0.1 vs 0.59 +/- 0.11 mumol/L, P < .05), and arganine (Arg) to ADMA ratio was significantly higher (155 +/- 53 vs 193 +/- 61, P < .01). No changes were observed for plasma nitric oxide end products (nitrite and nitrate) levels after GH treatment (21.9 +/- 14.9 vs 24.1 +/- 19.0 mumol/L, not significant). Basal forearm blood flow remained unchanged, whereas reactive hyperemia increased from 7.30 +/- 5.31 mL/100 mL forearm per minute before GH therapy to 13.18 +/- 7.30 mL/100 mL forearm per minute after 6 months of therapy (P < .001). There was a positive correlation between IGF-1 and cyclic guanosine monophosphate (r = 0.73, P < .0001), IGF-1 and reactive hyperemia (r = 0.63, P < .0001), and IGF-1 and Arg/ADMA ratio (r = 0.44, P < .01). Conversely, a negative correlation was found between IGF-1 and ADMA levels (r = -0.41, P < .02). At the end of the study period, fat-free mass, plasma glucose, and hemoglobin A(1c) levels significantly increased, even if they were still in the reference range, suggesting moderate alteration of glucose metabolism. In conclusion, in GHD patients, GH replacement contributes to decreased, to some extent, cardiovascular risk, reducing ADMA levels and improving Arg/ADMA ratio and endothelial dysfunction.