Evidence for hypermetabolism in boys with constitutional delay of growth and maturation.

Abstract

Children with constitutional delay of growth and maturation (CDGM) tend to be thin and have a growth pattern reminiscent of nutritional insufficiency. Our objective was to compare differences in nutrition, body composition, bone mineral density, and resting and total energy expenditure (REE/TEE) in boys with CDGM and controls. We hypothesized that an imbalance between energy intake and expenditure may contribute to the pathogenesis of CDGM. We conducted an observational, cross-sectional study at an outpatient clinical research center. Patients included 36 boys (8-17 yr): 12 with CDGM (short stature, delayed bone age and puberty, and no other pathology) and 12 height-matched (pre- or early-pubertal) and 12 age-matched (pubertal) healthy controls. Outcome measures included doubly labeled water studies (TEE), serum nutritional/hormonal markers, dual-energy x-ray absorptiometry, dietary analysis, and indirect calorimetry (REE). Nutritional markers were comparable among the groups. CDGM subjects had bone mineral density lower than age-matched controls (P < 0.01) but comparable with height-matched controls. Even though REE did not differ between groups, CDGM subjects had 25% higher caloric intake adjusted for fat-free mass (FFM) than height-matched controls (P < 0.05) and 78% higher caloric intake per kilogram FFM compared with age-matched controls (P < 0.00001). CDGM subjects had 46% (P < 0.05) and 91% (P < 0.001) higher TEE per kilogram FFM than height- and age-matched controls, respectively. CDGM subjects had lower IGF-I and testosterone than age-matched controls (P < 0.001) but levels were comparable with height-matched controls. Boys with CDGM have higher rates of overall energy expenditure compared with age- and size-matched controls. This increased metabolism may result in impaired tempo of growth. Additional studies are needed to determine whether augmenting nutrition to match their energy needs (with or without hormonal therapy) can improve linear and ponderal growth in patients with CDGM.