LDL SUBFRACTIONS IN ACROMEGALY - RELATION TO GROWTH-HORMONE AND INSULIN-LIKE GROWTH-FACTOR-I

Acromegaly is associated with changes in lipoprotein metabolism and an excess in cardiovascular mortality. We have examined low density lipo protein (LDL) subfraction distribution in 24 patients with active acro megaly and in controls matched for age, sex and body mass index. LDL w as subfractionated by density gradient ultracentrifugation. The concen tration of small dense LDL-III was significantly higher in the acromeg alic patients compared to the controls (94.2 +/- 44.9 versus 67.2 +/- 30.4 mg/dl, P < 0.05) and there was a concomitant reduction in the int ermediate subfraction LDL-II (124.8 +/- 31.3 versus 149.9 +/- 30.0 mg/ dl, P < 0.05). Univariate analysis showed that both growth hormone (GH ) and insulin-like growth factor (IGF)-I correlated with LDL-III and i nversely with LDL-II. Acromegalic patients were found to have lower he patic lipase (HL) and lipoprotein lipase (LPL) activities than control s (HL: 13.29 +/- 6.56 versus 21.58 +/- 7.27 mu mol FFA released/ml/h, P < 0.001; LPL: 7.22 +/- 3.04 versus 11.53 + 7.85 mu mol FFA released/ ml/h, P < 0.05) whereas plasma cholesteryl ester transfer protein (CET P) activity was significantly increased (8.15 +/- 1.81 versus 5.54 +/- 1.86 pmol/mu l/h, P < 0.001). Both GH and IGF-I were significantly as sociated with HL, LPL and CETP activities. Multivariate analysis on th is relatively small sample size showed that in normal subjects, trigly ceride and HL activity were the major determinants of LDL-III. In cont rast, GH and HDL were the main determinants in acromegaly, accounting for 32 and 24% in the variability of LDL-III respectively. In conclusi on, GH excess has a direct effect on LDL subfraction distribution. (C) 1997 Elsevier Science Ireland Ltd.