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Diagnosis and Treatment > Medication

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Angelo Paci Pharmacology and Drug Analysis Department, Gustave Roussy, Villejuif, France

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Ségolène Hescot INSERM U1185, Fac Med Paris Sud, Le Kremlin-Bicêtre, France
Nuclear Medicine and Endocrine Oncology Department, Gustave Roussy, Villejuif, France

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Atmane Seck Pharmacology and Drug Analysis Department, Gustave Roussy, Villejuif, France

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Christel Jublanc Assistance Publique-Hôpitaux de Paris, La Pitié-Salpetriere Hospital, Department of Endocrinology, Paris, France

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Lionel Mercier Pharmacology and Drug Analysis Department, Gustave Roussy, Villejuif, France

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Delphine Vezzosi CHU Larrey, Department of Endocrinology, Toulouse, France

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Delphine Drui CHU Nantes, Department of Endocrinology, Nantes, France

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Marcus Quinkler Endocrinology in Charlottenburg, Berlin, Germany

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Martin Fassnacht Endocrine and Diabetes Unit, Department of Medicine 1, University Hospital, University of Würzburg, Würzburg, Germany

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Eric Bruckert Assistance Publique-Hôpitaux de Paris, La Pitié-Salpetriere Hospital, Department of Endocrinology, Paris, France

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Marc Lombès INSERM U1185, Fac Med Paris Sud, Le Kremlin-Bicêtre, France

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Sophie Leboulleux Nuclear Medicine and Endocrine Oncology Department, Gustave Roussy, Villejuif, France

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Sophie Broutin Pharmacology and Drug Analysis Department, Gustave Roussy, Villejuif, France

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Eric Baudin INSERM U1185, Fac Med Paris Sud, Le Kremlin-Bicêtre, France
Nuclear Medicine and Endocrine Oncology Department, Gustave Roussy, Villejuif, France

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Summary

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.

Learning points

  • 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.

Taxonomy:
Clinical Overview, Gland/Organ, Adrenal, Topic, Obesity, Condition/ Syndrome, Adrenocortical carcinoma, Patient Demographics, Age, Adult, Gender, Male, Ethnicity, White, Country of Treatment, France, Diagnosis and Treatment, Signs and Symptoms, Dyslipidaemia, Hypercholesterolaemia, Investigation, Chromatography, Histopathology, LDL cholesterol, Triglycerides, Intervention, Chemotherapy, Radiotherapy, Medication, Etoposide, Fluorouracil, Gemcitabine, Mitotane, Statins, Related Disciplines, Oncology, Publication Details, Case Report Type, Error in diagnosis/pitfalls and caveats
DOI:
https://doi.org/10.1530/EDM-15-0135
Volume/Issue:
Volume 2016: Issue 1
Open access