Whole Body Nitrogen Kinetics and Their Relationship to Growth in Short Children Treated with Recombinant Human Growth Hormone

Abstract

We studied the effects of growth hormone on retention of 15N-labeled amino acids in 34 short, prepubertal, growth hormone-sufficient children and three growth hormone-deficient subjects. All 34 non-growth hormone-deficient children had apparently normal circulating growth hormone molecules and no mutations were detected in the growth hormone or IGF-I genes of any subjects. Fibroblasts from 34 children responded normally when challenged with recombinant human IGF-I. During the last 72 h of a 4-d challenge with recombinant human growth hormone (16 micrograms/kg body wt), retention of a mixed 15N-amino acid dose varied between 5.7 and 50.5%. Whole body protein synthesis, breakdown, and net anabolism calculated from the 15N kinetics were all increased by the acute growth hormone challenge. However, no routine clinical feature or laboratory determination correlated with the nitrogen retention response. After subsequent treatment (75 micrograms/kg three times a week) with recombinant human growth hormone for 1 y, there was a significant increase in height velocity, but this increase was not related significantly to pretreatment variables other than inversely to pretreatment height velocity. There was a significant (p = 0.03) correlation between the change in height velocity Z score and the degree of nitrogen retention to acute challenge with growth hormone, but this correlation was too weak (r = 0.37) to be of practical value in predicting the treatment growth response in an individual child.