Everolimus treatment among patients with tuberous sclerosis affects serum lipid profile.

BACKGROUND: The purpose of the study was to evaluate lipid homeostasis before and after treatment of everolimus, the mammalian target of the rapamycin (mTOR) inhibitor, among patients with tuberous sclerosis complex (TSC).

METHODS: The study group consisted of 15 patients with a diagnosis of subependymal giant cell astrocytoma (SEGA) related to TSC. The following lipid parameters were determined: total serum cholesterol (TCh), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total serum triglyceride (TG) concentration at baseline, then after three and 12 months of observation. The values were compared with those of age-matched healthy controls.

RESULTS: In the study group TCh, LDL and HDL levels at baseline were significantly higher than in the control group. TCh and LDL levels were positively correlated with baseline SDS-BMI in TSC patients. Everolimus treatment resulted in significant increases of TCh (from 192.04±40.51mg/dl to 210.74±51.12mg/dl and to 216.69±45.43mg/dl; p=0.0273) and LDL (from 113.21±38.72mg/dl to 133.88±50.71mg/dl and to 141.58±40.67mg/dl; p=0.0006) after three and 12 months respectively. The differences between the TCh and LDL levels at baseline and after 12 months of therapy were negatively correlated with baseline SDS-BMI. The observed increase of BMI after 12 months was correlated with increases in TCh and LDL levels.

CONCLUSIONS: Patients with TSC have disrupted lipid homeostasis before and during treatment with everolimus, which might be partially connected to the mTOR-dependent nutritional status of the patients. There is a need to develop strategies for children with TSC treated with everolimus, who experience hyperlipidemia.