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Decreased plasma cholesterol esterification and cholesteryl ester transfer in hypopituitary patients on
J A Beentjes1, A van Tol, W J Sluiter
1Department of Endocrinology, University Hospital Groningen, The Netherlands.
Insights
Glucocorticoid replacement therapy in hypopituitary patients impairs high-density lipoprotein (HDL) metabolism by decreasing cholesterol esterification and transfer. This may contribute to cardiovascular risk despite stable plasma lipids.
Area of Science:
- Endocrinology
- Lipid Metabolism
- Cardiovascular Risk
Background:
- Hypopituitarism is associated with increased cardiovascular risk.
- The impact of glucocorticoid replacement on high-density lipoprotein (HDL) metabolism in hypopituitary patients remains unclear.
- Key determinants of HDL remodeling include plasma lecithin:cholesterol acyl transferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP).
Purpose of the Study:
- To evaluate the influence of conventional glucocorticoid replacement therapy on plasma lipids, LCAT, CETP, PLTP activity, cholesterol esterification (EST), and cholesteryl ester transfer (CET) in hypopituitary patients.
- To investigate potential links between glucocorticoid treatment, HDL metabolism, and cardiovascular risk factors.
Main Methods:
- A study involving 24 hypopituitary patients with growth hormone deficiency, of whom 17 received cortisone acetate for adrenal insufficiency.
- Assessment of plasma lipids, LCAT, CETP, PLTP activity, and cholesterol esterification/transfer.
- Analysis of urinary cortisol metabolites, body mass index, fat mass, glucose, insulin, and insulin resistance.
Main Results:
- Glucocorticoid-treated patients showed lower plasma total and LDL cholesterol but similar HDL cholesterol and triglycerides.
- Plasma LCAT and CETP activities were significantly reduced (45% and 34%, respectively) in patients on glucocorticoids.
- Plasma cholesterol esterification and cholesteryl ester transfer were markedly decreased (80% and 58%, respectively), linked to lower LCAT and CETP activity.
Conclusions:
- Conventional glucocorticoid replacement in hypopituitary patients is associated with impaired HDL metabolism, specifically reduced cholesterol esterification and transfer.
- These metabolic alterations may contribute to the elevated cardiovascular risk observed in these patients, irrespective of overall plasma lipid levels.
- Glucocorticoids differentially regulate CETP and PLTP, impacting HDL remodeling pathways.
Abstract:
Cardiovascular risk is increased in hypopituitary patients. No data are available with respect to the effect of glucocorticoid replacement therapy on high density lipoproteins (HDL) metabolism in such patients. Plasma lecithin:cholesterol acyl transferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are important determinants of HDL remodelling. The possible influence of conventional glucocorticoid replacement on plasma lipids, plasma LCAT, CETP and PLTP activity levels, as well as on plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) was evaluated in 24 consecutive hypopituitary patients (12 men and 12 women) with untreated growth hormone deficiency of whom 17 had adrenal insufficiency and were treated with cortisone acetate, 25 to 37.5 mg daily. Twenty-three patients were on stable levothyroxin therapy and 22 patients used sex steroids. Urinary excretion of cortisol and cortisone metabolites was higher (p<0.001) in glucocorticoid-treated patients. Body mass index (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 cholesterol 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 glucocorticoid treatment. Multiple regression analysis showed that these effects were independent of gender and fat mass. In glucocorticoid-receiving patients, plasma EST and CET were decreased by 80% (p<0.01) and by 58% (p<0.05), respectively. These changes were at least partly attributable to lower LCAT and CETP activity levels. In contrast, plasma PLTP activity was not different between patients with and without glucocorticoid treatment, suggesting that 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 associated 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 cardiovascular risk in glucocorticoid-treated hypopituitary patients, despite a lack of deterioration in plasma lipids.