LEUCINE METABOLISM IN PATIENTS WITH CUSHINGS-SYNDROME BEFORE AND AFTER SUCCESSFUL TREATMENT

OBJECTIVE Results from studies on the effect of glucocorticosteroids on protein turnover in both rat and man have been conflicting. The alm of this study was to investigate the primary cause of muscle wasting in patients with Cushing's syndrome. DESIGN Studies of whole body 1-C-14-leucine turnover in patients with Cushing's syndrome before and after successful treatment, and in control subjects. PATIENTS Eleven patients with Cushing's syndrome before and after (n = 5) treatment and 11 control subjects. MEASUREMENTS Whole body 1-C-14-leucine turnover to determine leucine metabolic clearance rate, leucine production rate, leucine oxidation rate and leucine incorporation into protein. RESULTS Plasma leucine concentration (mean +/- SEM 100 +/- 6 mumol/1), leucine metabolic clearance rate (9.97 +/- 0.11 mumol/min/kg), leucine turnover (0.98 +/- 0.11 mumol/min/kg) and leucine incorporation into protein (0.71 +/- 0.09 mumol/min/kg) were all significantly reduced in patients with Cushing's syndrome compared with control subjects (122 +/- 6 mumol/l, P < 0.05; 13.61 +/- 1.27 mumol/min/kg, P < 0.05; 1.65 +/- 0.12 mumol/min/kg, P < 0.05; 1.46 +/- 0.10 mumol/min/kg, P < 0.001, respectively). Leucine oxidation rate was similar in the patients with Cushing's syndrome and control subjects. When leucine metabolism was expressed in terms of lean body mass (LBM) in live patients with Cushing's syndrome and 11 control subjects, leucine MCR, leucine turnover and leucine oxidation were not significantly different in the two groups. However, leucine incorporation into protein was significantly reduced (P < 0.001) in the patients with Cushing's syndrome (1.07 +/- 0.20 mumol/min/kg LBM) compared with control subjects (1.95 +/- 0.11 pmol/min/kg LBM). CONCLUSION We conclude from these studies that the muscle wasting associated with Cushing's syndrome is primarily due to a reduction in protein synthesis.