Mitotane induced HDL-cholesterol elevation: A retrospective cohort study

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 723-739-Lipids: Therapeutics & Case Reports
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-729
Ferhat Deniz*1, Hadil Bazerbashi2, Camilo Jimenez3, Rena Vassilopoulou-Sellin4 and Mouhammed Amir Habra4
1Gulhane Military Medical Academy, Ankara, Turkey, 2University of Texas-Houston, School of Public Health, Houston, TX, 3UT MD Anderson Cancer Cntr, Houston, TX, 4The University of Texas MD Anderson Cancer Center, Houston, TX
Background:  Mitotane (o, p’-DDD) has been used to treat adrenocortical carcinoma (ACC) since the 1960s.  Mitotane use is associated with wide range of metabolic and pharmacological alterations. HDL increase in association with mitotane was described in a small number of patients who had normal triglycerides.  Many questions remain unanswered regarding the true prevalence of HDL elevation and its significance in the context of mitotane therapy. Better understanding of the mechanism of this HDL rise could have important implication in the quest to find new drugs to raise HDL cholesterol.

Methods:  This is a retrospective cohort study of ACC patients seen at MD Anderson Cancer Center from 1998-2011. The main goal is to describe lipid changes and in particular HDL in association with mitotane use. Institutional Review board approval was obtained. Patients were included if baseline lipid profile was available before the initiation of mitotane therapy and if they had a minimum of one lipid panel during mitotane therapy with corresponding mitotane level. Clinical data were summarized including the simultaneous use of lipid lowering agents. Descriptive statistics and comparative analytic studies were done. Statistical software SAS 9.1.3 (SAS Institute, Cary, NC) and STATA 12 (STATA, Austin, TX) were used for all the analyses.

Results:  A total of 330 patients were included in our ACC database including 235 patients who received mitotane therapy during their follow-up. Only 39 subjects met inclusion criteria (27 female and 12 male) and had satisfactory documentation of lipid changes. Median age (range) was 52 years (13-77years). At baseline, mean HDL, LDL, and triglycerides (± SD) were 53.1mg/dl (±16.1), 113mg/dl (± 45.7), and 148.8mg/dl (± 23.1) respectively. At the time of HDL peak, the mean HDL, LDL, and triglycerides (± SD) were 85.4mg/dl (±33.7.1), 146.3 mg/dl (± 65.8), and 152.2 mg/dl (± 114.4).  The change in HDL was statistically significant (p=.00000) with a mean increase of 32.3mg/dl (95% CI 22.3-42.3). Median (range) serum mitotane level at the peak was 9.3 microgram/ml (1.9-23 microgram/ml).

In contrast to earlier reports, we could not find a significant difference in mean peak HDL between patients who had normal (n=30) or elevated triglycerides (n=9) at baseline (p=0.7356). Similarly, no significant HDL increase was seen by ACC stage or gender.

Conclusion: Mitotane use is associated with significant increase in HDL cholesterol. Discovering this mechanism is important as it might help with the drug discovery of HDL raising agents.

Nothing to Disclose: FD, HB, CJ, RV, MAH

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