Context Growth hormone (GH) acutely increases body protein by stimulating protein synthesis and reducing protein oxidation.

Objective To determine whether these changes in protein metabolism are sustained in long-term GH excess, and reversed by correction.

Design A cross-sectional study in 16 acromegalic and 18 normal subjects, and a longitudinal study in which acromegalic subjects were studied before and after short-term (n=8) or long-term (n=10) treatment.

Setting A Clinical Research Centre.

Main Outcome Measures Whole-body rates of leucine appearance (leucine Ra, an index of protein breakdown), leucine oxidation and non-oxidative leucine disposal (NOLD, an index of protein synthesis) estimated using infusion of 1-[13C] leucine.

Results Leucine Ra and NOLD were greater (p<0.01) in acromegalic compared to normal subjects while leucine oxidation did not differ. Leucine oxidation increased significantly (p<0.05) after short-term treatment but returned to baseline after long-term treatment. Both leucine Ra and NOLD fell significantly (p<0.05) after short and long-term treatment. Results were not affected by adjustment for body composition.

Conclusions In acromegalic subjects, protein breakdown and synthesis are increased, while protein oxidation does not differ from normal subjects. Protein oxidation increases transiently, while protein breakdown and synthesis are stably reduced after treatment. As protein oxidation represents irreversible loss, we conclude that the normal state of protein oxidation found in acromegaly and after long-term treatment represents metabolic adaptation, which maintains protein mass at a steady state after stable changes in GH status.