Familial Isolated Growth Hormone Deficiency Is Associated with Hypertension, Central Obesity and Dyslipidemia But not the Classical Syndrome X
We have described a splice mutation in the GHRH receptor gene (G to A at position +1 , intron 1) in Itabaianinha county, Sergipe, Brazil. These genetically homogeneous individuals provide a unique opportunity to investigate the effects of isolated growth hormone deficiency [GHD] on cardiovascular risks. Therefore, we studied 16 dwarfs with GHD and no past of growth hormone therapy (8M:8F,49±14 yrs) and 31 age-matched normal controls [C] (12M:19F,44±12 yrs). We have examined insulin-like growth factor 1(IGF-1), arterial blood pressure, body mass index (BMI), waist-to-hip ratio (WHR), body composition by near infra-red interactance,leptin,serum lipids, uric acid, fasting glucose and insulin. IGF-1 in GHD was markedly lower (2.7±1.8 vs 154.9±82 ng/mL; p<0.001). Systolic blood pressure was higher in GHD (147±37 vs 129±24 mmHg; p=0.046) but diastolic blood pressure was similar (84±16 vs 80±16 mmHg; p=NS). BMI (22.9±4.1 vs 24.4±3.8 Kg/m2 ;p=NS) and leptin (11±8.9 vs 10.2±11.3 ng/mL;p=NS) were similar (GHD vs C), but WHR (0.97±0.08 vs 0.90±0.08; p=0.01) and % of fat mass (34±7 vs 21±10 %;p<0.001)were higher in GHD. Total cholesterol (236±53 vs 195±38 mg/dL;P=0.003) and LDL-C (165 ±47 vs 133±32 mg/dL;p=0.009) were higher in GHD but no differences were observed in HDL-C (40±9 vs 38±7 mg/dL;p=NS), apo B (1.16±0.36 vs 1.33±0.96 g/L; p=NS) and triglycerides (158±117 vs 115±62 mg/dL;p=NS). Uric acid was higher in GHD (4.0±1.2 vs 3.3±0.8; p=0.02). Despite central obesity and hypertension, fasting glucose (86±11 vs 87±14 mg/dL;p=NS),fasting insulin (2.9±2.4 vs 4.3±3.4 μU/mL;p=NS) and insulin/glucose ratio (0.03±0.03 vs 0.05±0.03μU/mL;p=NS) were smaller but not significantly in GHD. We conclude that GHD due to this GHRH receptor mutation is associated with systolic hypertension, central obesity and dyslipidemia with some features different from the classical syndrome X. These data suggest that in GHD another mechanism different from insulin resistance participate in the pathogenesis of hypertension and metabolic alterations.