Dyslipidemia causes overestimation of plasma mitotane measurements.
Mitotane (o,p'-DDD) is the standard treatment for advanced adrenocortical carcinoma (ACC). Monitoring of plasma mitotane levels is recommended to look for a therapeutic window between 14 and 20mg/L, but its positive predictive value requires optimization. We report the case of an ACC patient with a history of dyslipidemia treated with mitotane in whom several plasma mitotane levels >30mg/L were found together with an excellent neurological tolerance. This observation led us to compare theoretical or measured o,p'-DDD and o,p'-DDE levels in a series of normolipidemic and dyslipidemic plasma samples to explore potential analytical issues responsible for an overestimation of plasma mitotane levels. We demonstrate an overestimation of mitotane measurements in dyslipidemic patients. Mitotane and o,p'-DDE measurements showed a mean 20% overestimation in hypercholesterolemic and hypertriglyceridemic plasma, compared with normolipidemic plasma. The internal standard p,p'-DDE measurements showed a parallel decrease in hypercholesterolemic and hypertriglyceridemic plasma, suggesting a matrix effect. Finally, diluting plasma samples and/or using phospholipid removal cartridges allowed correcting such interference.


CONCLUSIONS
Hypercholesterolemia (HCH) and hypertriglyceridemia (HTG) induce an overestimation of plasma mitotane measurements.We propose a routine monitoring of lipidemic status.We propose optimized methodology of measurement before interpreting high plasma mitotane levels.
Pharmacology and Drug Analysis Department , Gustave Roussy, Villejuif , France.
Angelo
A
Paci
INSERM U1185, Fac Med Paris Sud, Le Kremlin-Bicêtre, France; Nuclear Medicine and Endocrine Oncology Department, Gustave Roussy, Villejuif, France.
Ségolène
S
Hescot
Pharmacology and Drug Analysis Department , Gustave Roussy, Villejuif , France.
Atmane
A
Seck
Assistance Publique-Hôpitaux de Paris, La Pitié-Salpetriere Hospital, Department of Endocrinology , Paris , France.
Christel
C
Jublanc
Pharmacology and Drug Analysis Department , Gustave Roussy, Villejuif , France.
Lionel
L
Mercier
CHU Larrey, Department of Endocrinology , Toulouse , France.
Delphine
D
Vezzosi
CHU Nantes, Department of Endocrinology , Nantes , France.
Delphine
D
Drui
Endocrinology in Charlottenburg , Berlin , Germany.
Marcus
M
Quinkler
Endocrine and Diabetes Unit, Department of Medicine 1, University Hospital, University of Würzburg , Würzburg , Germany.
Martin
M
Fassnacht
Assistance Publique-Hôpitaux de Paris, La Pitié-Salpetriere Hospital, Department of Endocrinology , Paris , France.
Eric
E
Bruckert
INSERM U1185, Fac Med Paris Sud , Le Kremlin-Bicêtre , France.
Marc
M
Lombès
Nuclear Medicine and Endocrine Oncology Department , Gustave Roussy, Villejuif , France.
Sophie
S
Leboulleux
Pharmacology and Drug Analysis Department , Gustave Roussy, Villejuif , France.
Sophie
S
Broutin
INSERM U1185, Fac Med Paris Sud, Le Kremlin-Bicêtre, France; Nuclear Medicine and Endocrine Oncology Department, Gustave Roussy, Villejuif, France.
Eric
E
Baudin