Abnormal prorenin processing in growth hormone deficiency.
Growth hormone deficiency (GHD) is associated with increased premature cardiovascular (CV) mortality. Abnormal cardiac structure and function, including autonomic adrenergic dysfunction as detected by heart rate variability analysis, have been described in GHD. Abnormal prorenin processing resulting in a reduced renin/prorenin ratio has been correlated with cardiac autonomic dysfunction, an established risk factor for CV mortality, in diabetic patients. We investigated renin/prorenin ratios in untreated GHD patients (n=31) and in a group of GHD patients treated with GH (n=23) and compared both groups to a group of 59 normal control subjects. The treated GHD group was replaced with GH for a mean duration of 49.4+/-6.7 months. The mean renin/prorenin ratios were 0.0765+/-0.0089 in the untreated GHD group, 0.113+/-0.018 in the treated GHD group, and 0.304+/-0.029 in the control group (P<0.01, untreated GHD or treated GHD vs. normal controls; P=NS, untreated GHD vs. treated GHD). These results demonstrate that GHD is characterized by abnormal prorenin processing implicating concomitant cardiac autonomic adrenergic dysfunction, a risk factor for increased CV mortality. GH treatment resulted in a non-significant trend towards normalizing this defect.