Genetics
Glucocorticoid replacement erases the CETP promoter variant's link to HDL cholesterol in hypopituitary patients (Clin Endocrinol (Oxf) 2008)
Original title: Glucocorticoid replacement is associated with hypertriglyceridaemia, elevated glucose and higher non-HDL cholesterol and may diminish the association of HDL cholesterol with the -629C>A CETP promoter polymorphism in GH-receiving hypopituitary patients
In 165 GH-replaced hypopituitary patients (117 also on glucocorticoid replacement, 48 ACTH-sufficient), glucocorticoid-treated subjects had higher non-HDL cholesterol (P = 0.05), triglycerides (P = 0.004), and prevalence of elevated glucose or diabetes (P = 0.04), though HDL cholesterol itself was not decreased. Since glucocorticoid replacement is known to markedly lower plasma CETP activity, the study tested the -629C>A CETP promoter polymorphism against HDL cholesterol: in ACTH-sufficient subjects, -629 A-allele carriers had significantly higher HDL cholesterol than -629CC homozygotes (P = 0.04), independently confirmed by regression (P = 0.03), but this association disappeared in glucocorticoid-treated subjects (P = 0.13). Conventional glucocorticoid replacement therefore appears to diminish the normal association between this CETP gene variant and HDL cholesterol.
Original abstract
Objectives: The effect of glucocorticoid substitution on the prevalence of metabolic syndrome components (NCEP ATP III criteria) and serum lipid levels was determined in GH-replaced hypopituitary patients. As glucocorticoid replacement is associated with a pronounced decrease in plasma cholesteryl ester transfer protein (CETP) activity, we also tested associations of HDL cholesterol with the -629C>A CETP promoter polymorphism in subjects with and without ACTH deficiency.
Design And Patients: In a university setting, we retrieved protocolized clinical and laboratory data from 165 adult hypopituitary patients, who had received GH for 1 year.
Results: After adjustment for age, sex and smoking, non-HDL cholesterol (P = 0.05) and triglycerides (P = 0.004) were higher, but HDL cholesterol was not decreased in 117 glucocorticoid (mainly cortisone acetate in two divided doses) receiving subjects compared to 48 ACTH-sufficient subjects. The prevalence of elevated plasma glucose and/or diabetes (P = 0.04) and hypertriglyceridaemia (P = 0.005), but not of other metabolic syndrome components, was higher in glucocorticoid-replaced subjects. HDL cholesterol was higher in -629 A allele carriers compared to -629CC homozygotes in ACTH-sufficient subjects (P = 0.04), but not in glucocorticoid-treated subjects (P = 0.13). Multiple linear regression analysis demonstrated that only in ACTH-sufficient subjects, HDL cholesterol was independently related to this CETP gene variation (P = 0.03).
Conclusions: In GH- and glucocorticoid-replaced hypopituitary patients, serum non-HDL cholesterol and triglycerides are higher and the prevalence of hyperglycaemia is increased, but HDL cholesterol is not decreased. Conventional glucocorticoid replacement appears to diminish the association of HDL cholesterol with a common CETP gene variation.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.