Amino acids as substrates in children with growth hormone deficiency and hypoglycemia

In order to investigate the role of amino acid (AA) substrates in the hypoglycemia associated with human growth hormone (hGH) deficiency, we measured 12-hour fasting blood glucose and total quantitative AA concentrations in 11 children with hGH deficiency during three study periods: (1) before hGH replacement; (2) after 12 months of hGH treatment; and (3) after discontinuation of hGH for three months. The results were compared to studies in 16 control subjects. Fasting blood glucose concentrations were significantly (P less than .05) lower in the hGH-deficient children prior to hGH treatment as compared to the control subjects (67.0 +/- 5.3 vs 80.7 +/- 5.3 mg/100 ml, mean +/- SE). Fasting total serum AA concentrations were similar in the patients and in the control subjects; however, after 12 months of hGH replacement, there was a significant (P less than .01) elevation of serum AA (2,750 +/- 170 vs 2,283 micromoles/liter). Fasting serum concentrations of alanine, glycine, arginine, and tryptophan were also significantly elevated (P less than .01) with hGH treatment; ornithine, tyrosine, lysine, methionine, and phenylalanine showed lesser elevations (P less than 0.5), whereas threonine decreased significantly (P less than 0.01). The fasting hypoglycemia seen with isolated hGH deficiency is not an AA substrate-limited disorder. The finding of increased concentrations of AA with hGH replacement suggests increased retention of nitrogen and synthesis of AA for gluconeogenesis due to availability of other substrates.