The effect of hypercortisolism treatment on dyslipidemia in Cushing syndrome: systematic review and meta-analysis

Introduction: Cushing syndrome (CS) is a clinical condition caused by increased plasma cortisol levels and characterized by high cardiovascular mortality. Among the metabolic effects of CS and its treatment, glycaemic disturbances have been investigated in depth, while data on dyslipidemia is still lacking. Objectives: Our study aims at evaluating the effects of CS treatment on serum lipid levels. Materials and methods: A literature search was conducted using PubMed, Scopus, and EMBASE databases to investigate the effects of CS treatment on serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triglycerides (TG). Before-after analysis and subgroup analysis were performed. Results: Twenty-nine observational or interventional studies (51.7% of good quality) were included in the quantitative analysis. Treatment of CS led to clinically and statistically significant decrease in serum TC (MD -26.49; 95% CI: -29.95, -23.04; p < 0.00001), LDL-c (MD -18.44; 95% CI: -21.30, -15.57; p < 0.00001), and TG levels (MD -17.77; 95% CI: -22.70, -12.84; p < 0.00001), with no significant changes in HDL-c levels (MD -2.34; 95% CI: -6.96, 2.28; p= 0.32). Subgroup analysis showed greater decrease in TC levels in subjects with adrenal hypercortisolism, in those treated with steroidogenesis inhibitors and in those with treatment duration equal or longer than 12 months. In addition, CS treatment significantly decreased blood glucose (BG) levels, body mass index (BMI), waist circumference (WC), and insulin resistance index. Conclusion: Our study demonstrate a significant improvement in serum lipid levels after treatment of CS. Since the cardiovascular complications of hypercortisolism depend on several factors, further studies are needed to determine whether this directly translates into an adequate reduction in the risk of major cardiovascular events.