WHOLE-BODY LEUCINE TURNOVER IN ADULTS ON CONVENTIONAL TREATMENT FOR HYPOPITUITARISM

This study has investigated protein metabolism in adults with hypopituitarism before and after growth hormone (GH) replacement and in matched controls. Whole-body leucine turnover was measured in 16 GH-deficient adult hypopituitary patients (nine females and seven males) on standard thyroid, adrenal and sex hormone replacement and in 20 normal controls using primed continuous infusion of L-[ 1 - C-13]leucine. In seven of the patients, leucine turnover was restudied following 6 months treatment with biosynthetic human GH (0.025-0.05 IU/kg body wt daily, with the final dose determined by patient tolerance). Compared with normal controls, hypopituitary patients had significantly reduced leucine flux (mean +/- SD: 97.8 +/- 24.9 vs 131.0 +/- 23.0 mumol . h-1 . kg-1: p < 0.001), reduced leucine incorporation into protein (80.4 +/- 20.9 vs 108.8 +/- 19.6 mumol . h-1 . kg-1; p<0.001) and reduced leucine oxidation(17.4 +/- 4.8 vs 22.2 +/- 8.1 mumol . h-1 . kg-1; p < 0.05). Leucine turnover was similar in male and female patients. In the patients, leucine flux correlated positively with body weight (rho = 0.51. p < 0.05) and leucine incorporation in protein correlated positively with lean body mass (rho = 0.55, p < 0.05) and in male patients leucine flux correlated positively with serum insulin-like growth factor I (IGF-I) levels (rho = 0.71, p < 0.05). No significant relationship was observed with age or duration of hypopituitarism. Growth hormone replacement therapy did not produce a uniform effect on leucine metabolism. Mean values of leucine flux, oxidation and incorporation into protein increased, although the differences were not statistically significant. The patients on higher GH doses and with a higher serum IGF-I response were those who demonstrated an increase in leucine turnover. We conclude that leucine turnover in hypopituitary adults is reduced compared with normal controls. The effect of GH treatment for 6 months at conventional doses in hypopituitary adults is not uniform and may be dose-dependent.