Protein metabolism in acromegaly: differential effects of short- and long-term treatment.

CONTEXT

GH acutely increases body protein by stimulating protein synthesis and reducing protein oxidation.

OBJECTIVE

The objective of the study was to determine whether these changes in protein metabolism are sustained in long-term GH excess and reversed by correction.

DESIGN

We conducted 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

The study was conducted at a clinical research center.

MAIN OUTCOME MEASURES

Whole-body rates of leucine appearance (leucine Ra; an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (NOLD; an index of protein synthesis) estimated using infusion of 1-[13C] leucine were measured.

RESULTS

Leucine Ra and NOLD were greater (P<0.01) in acromegalic compared with normal subjects, whereas 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 decreased significantly (P<0.05) after short- and long-term treatment. Adjustment for body composition did not affect results.

CONCLUSIONS

In acromegalic subjects, protein breakdown and synthesis are increased, whereas protein oxidation does not differ from normal subjects. Protein oxidation increases transiently, whereas protein breakdown and synthesis are stably reduced after treatment. Because 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.