Role of Nutrition and Hormones in Boys With Disordered Growth

We propose a pilot study to examine the role of nutrition and its interaction with growth hormone (GH) therapy in boys with very short stature who also have delayed bone age characteristic of constitutional delay of growth and maturation (CDGM). Recent studies have suggested that insufficient caloric intake may contribute to the pathophysiology of CDGM. This prompted us to consider whether nutritional intervention may benefit children with severe short stature who also have CDGM. To investigate this further, we would like to enroll a total of 20 boys (10-15 boys in Jacksonville, Florida and 5-10 boys at the NIH, Bethesda, Maryland), ages 7-10 years, who are otherwise healthy, but have significant short stature (height SDS less than -2.25 = the current FDA approved indication for the use of GH in idiopathic short stature), delayed bone age (greater than 12 months below chronologic age), and low BMI and weight-for-height (less than 25th percentile). Ten boys will be randomized to receive observation for 6 months, followed by GH therapy for 12 months. Ten boys will be randomized to receive daily liquid nutritional supplementation for 6 months, followed by combined GH therapy and nutritional supplementation for 12 months. For all subjects, weight gain will be monitored at 2 weeks, 4 weeks, and then monthly. Height gain and body composition (using skin-fold thickness calipers and bioelectric impedance analysis) will be assessed every 3 months. Total energy expenditure, three-day dietary history, bone age, body composition/bone mineral density (using dual energy X-ray absorptiometry), and laboratory studies (IGF1, IGFBP3, pre-albumin, transferrin, ghrelin, fasting insulin, glucose, and lipid profile) will be obtained at baseline and then every 6 months. We hypothesize that nutritional supplementation alone can lead to small improvements in linear growth and lean body mass accrual, but when combined with GH therapy, can augment the anabolic actions of GH, thereby resulting in even greater improvements in linear growth velocity and lean body mass accrual than GH alone. If the data from this study confirm this trend, we would then like to proceed with a larger study, appropriately powered based on the results of this pilot.