Serum leptin and body composition in children with familial GH deficiency (GHD) due to a mutation in the growth hormone-releasing hormone (GHRH) receptor

OBJECTIVE The relationship between GH, body composition and leptin in child ren remains ill-defined. We have therefore examined the impact of severe GH deficiency (GHD) due to a mutation in the GHRH receptor on serum leptin co ncentrations and body composition in childhood. PATIENTS 12 affected children and young people (GHD) (4M:8F, age 5.4-20.1 y ears, 8 Tanner stage (TS) 1-2, 4 TS 3-5) and 40 healthy controls (C) from t he same region (13M:27F, age 5.3-18.4 years, 20 TS 1-2, 20 TS 3-5). METHODS Percent body fat was determined by infrared interactance, from whic h the amounts of fat mass (FM, kg) and fat free mass (FFM, kg) were derived . Serum leptin concentrations were measured in a single fasted, morning ser um sample and results expressed as a concentration and as leptin per unit f at mass (L/FM, ng/ml/kg). To control for differences in sex and pubertal ma turation, leptin standard deviation scores (leptin SDS) were calculated usi ng normative data from UK children. RESULTS FFM was significantly lower in GHD children than in controls (TS 1- 2 P<0.05, TS 3-5 P<0.001). FM did not differ significantly between the two groups. Serum leptin concentrations, leptin per unit fat mass and leptin SD S were significantly elevated in GHD children both peripubertal and puberta l compared with controls. Using all subjects, stepwise multiple linear regr ession with FM, FFM, age, puberty and sex as explanatory variables and lept in concentration as the dependent variable indicated that 59% of the variab ility in leptin could be accounted for by FM (+, 45%), FFM (-, 9%) and sex (+, 5%) (P<0.001). However on inclusion of GH deficiency (coded GHD=1, cont rol=2) as an explanatory variable 73% of the variability in leptin was expl ained by FM (+, 45%), GHD (-, 22%) and sex (+, 6%) (P<0.001). CONCLUSIONS These data indicate that severe GH deficiency in children is as sociated with elevated leptin concentrations, irrespective of sex or pubert al stage. This increase is not associated with differences in fat mass but is related to reduced fat free mass in GH deficiency. Furthermore in this p opulation there may be an additional effect of GH deficiency on leptin, ind ependent of the influences of sex and body composition.