Influence of Plasma Triglyceride Levels on Mitotane Therapeutic Drug Monitoring in Adrenocortical Carcinoma: Translational Implications from a Case Report

Background: Mitotane is the cornerstone adjuvant and palliative treatment for adrenocortical carcinoma (ACC), requiring strict therapeutic drug monitoring (TDM) due to its narrow therapeutic window and high inter- and intra-individual pharmacokinetic variability. As a highly lipophilic compound, mitotane may be influenced by plasma lipid levels; however, current TDM protocols do not systematically incorporate lipid profile assessment. We report a case illustrating the clinical impact of hypertriglyceridemia on measured mitotane plasma concentrations. Methods: We retrospectively analyzed clinical, biochemical, and pharmacokinetic data from a patient with metastatic ACC treated with oral mitotane. Plasma mitotane concentrations were correlated with triglyceride and cholesterol levels using Spearman’s rank correlation analysis. Results: A 50-year-old male with metastatic ACC experienced abrupt fluctuations in mitotane plasma concentrations despite stable dosing. Supratherapeutic mitotane levels coincided with episodes of marked hypertriglyceridemia. A significant positive correlation was observed between triglyceride levels and plasma mitotane concentrations (ρ = 0.802, p < 0.001), as well as with total cholesterol (ρ = 0.658, p < 0.001). Conclusions: This case highlights a clinically relevant interaction between triglyceride levels and measured mitotane concentrations. Incorporating routine lipid profile assessment into mitotane TDM protocols may improve interpretation of plasma levels and therapeutic decision-making. Prospective studies are warranted to validate these findings and refine monitoring strategies.