Decreased plasma cholesterol esterification and cholesteryl ester transferin hypopituitary patients on glucocorticoid replacement therapy

Cardiovascular risk is increased in hypopituitary patients. No data are ava ilable with respect to the effect of glucocorticoid replacement therapy on high density lipoproteins (HDL) metabolism in such patients. Plasma lecithi n:choresterol acyl transferase (LCAT), cholesteryl ester transfer protein ( CETP) and phospholipid transfer protein (PLTP) are important determinants o f HDL remodelling. The possible influence of conventional glucocorticoid re placement on plasma Lipids, plasma LCAT, CETP and PLTP activity levels, as well as on plasma cholesterol esterification (EST) and cholesteryl ester tr ansfer (CET) was evaluated in 24 consecutive hypopituitary patients (12 men and 12 women) with untreated growth hormone deficiency of whom 17 had adre nal insufficiency and were treated with cortisone acetate, 25 to 37.5 mg da ily. Twenty-three patients were on stable levothyroxin therapy and 22 patie nts used sex steroids. Urinary excretion of cortisol and cortisone metaboli tes was higher (p < 0.001) in glucocorticoid-treated patients. Body mass in dex (p < 0.08) and fat mass (p < 0.12) were not significantly different in patients receiving and not receiving glucocorticoids. Fasting blood glucose , plasma insulin and insulin resistance were similar in the groups. Plasma total (p < 0.05) and very low + low density lipoprotein cholesterol (p < 0. 01) were lower in patients receiving glucocorticoids, whereas HDL chorester ol and plasma triglycerides were not different between patients treated and not treated with glucocorticoids. Plasma LCAT activity was 45% lower (p < 0.02) and CETP activity was 34% lower (p < 0.05) in patients on glucocortic oid treatment. Multiple regression analysis showed that these effects were independent of gender and fat mass. In glucocorticoid-receiving patients, p lasma EST and CET were decreased by 80% (p < 0.01) and by 58% (p < 0.05), r espectively. These changes were at least partly attributable to lower LCAT and CETP activity levels. In contrast, plasma PLTP activity was not differe nt between patients with and without glucocorticoid treatment, suggesting t hat exogenous glucocorticoids exert a different regulatory effect on plasma CETP compared to PLTP. In conclusion, this preliminary study suggests that conventional glucocorticoid replacement in hypopituitary patients is assoc iated with a decrease in plasma cholesterol esterification and cholesteryl ester transfer, indicating that these steps in HDL metabolism are impaired. Such abnormalities in HDL metabolism could be involved in increased cardio vascular risk in glucocorticoid-treated hypopituitary patients, despite a l ack of deterioration in plasma lipids.