Abstract

Abstract Introduction Cushing syndrome (CS) patients have an increased mortality rate, primarily due to increased cardiovascular and cerebrovascular disease. We postulated that lipoprotein or lipid profiles might underlie this risk. Methods We measured traditional lipid panels (Cholesterol, TC; calculated low density lipoprotein, LDL; triglycerides, TG; high density lipoprotein, HDL) by Abbot enzymatic assay and lipoprotein particles (particle size and number for HDL, LDL and VLDL) by nuclear magnetic resonance spectroscopy in CS patients before and after surgical remission. Values are shown as median (IQR or range). Results After initial evaluation, 41 subjects (median age 53 (IQR 39-63) years; 27 female) had presumed Cushing's disease (CD, n=23), ectopic ACTH secretion (EAS, n=17), or adrenal adenoma (AA, n=1). Fourteen were on chronic statin therapy. All median lipid values were normal except HDL, at 55mg/dl (range 27 - 59mg/dl, normal (RR) <60). Twenty-six patients had decreased HDL; of these, other abnormal values included TC and LDL (n=4), TG (n=4), TC, LDL, TG (n=2), LDL and TG (n=2) or LDL only (n=2). Other elevated LDL levels occurred alone (n=1) or with TC (n=2). Three patients had only an increase in TC, LDL, or TG. Median LDL particle number was increased at 1015 (IQR 809-1353; RR <1000), with normal particle size. Eighteen patients had increased LDL particle number (1005 - 2989); 7/18 had increased TC and/or LDL. The median particle size and number for HDL and VLDL were normal in all patients except for one with an increased VLDL particle number of 199.7 (RR 6.8 - 126.1; TGs 302mg/dl, LDL 61 mg/dl, HDL 36 mg/dl, Chol 158 mg/dl). Sixteen subjects with CD (n=10), EAS (n=5) or AA (n=1) (13 females, median age 53 (IQR 40-58) years) had data at last study visit (LSV) after surgical remission. At LSV (median 13 months, range 3-26 months) abnormal preoperative LDL particle size persisted in 5/10, with new abnormalities (to 1450nm) in 3 patients. Initially high LDL and TC normalized in 3/6 and 4/5 patients. Abnormal HDL values were new in 2 patients and persisted in 7/8 from baseline. HDL particle number was low in two of these patients, while one with an HDL of 90mg/dl had increased particle size (10.6nm). TG and VLDL particle number and size remained normal except for one patient with low values. A statistically significant decrease (p=0.03) of median VLDL particle size from 49.5 nm (IQR 47.8-52.5) to 45.5nm (IQR 43.3–49.6), was noted at LSV. Conclusions While the numbers are small, these data suggest that the moderate cardiovascular risk conferred by elevated LDL particle size and low HDL persisted for up to 26 months of remission. Improved initiation and modification of treatment for these abnormalities might improve outcomes. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

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