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

Clin Endocrinol (Oxf). 2008 Sep;69(3):359-66. doi: 10.1111/j.1365-2265.2008.03196.x. Epub 2008 Jan 23.

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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Cholesterol / blood*
  • Cholesterol Ester Transfer Proteins / genetics*
  • Cholesterol Ester Transfer Proteins / physiology
  • Female
  • Genetic Linkage
  • Glucocorticoids / adverse effects*
  • Glucocorticoids / therapeutic use
  • Hormone Replacement Therapy / adverse effects
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / chemically induced*
  • Hypertriglyceridemia / epidemiology
  • Hypopituitarism / blood
  • Hypopituitarism / drug therapy*
  • Hypopituitarism / genetics
  • Male
  • Metabolic Syndrome / chemically induced
  • Metabolic Syndrome / epidemiology
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prevalence
  • Promoter Regions, Genetic
  • Young Adult

Substances

  • Blood Glucose
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Glucocorticoids
  • Human Growth Hormone
  • Cholesterol