Diagnosis and Treatment > Investigation > Triglycerides

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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.

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Satoru Sakihara Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan

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Kazunori Kageyama Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan

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Satoshi Yamagata Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan

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Ken Terui Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan

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Makoto Daimon Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan

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Toshihiro Suda Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan

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Summary

ACTH-dependent Cushing's syndrome includes Cushing's disease and ectopic ACTH syndrome (EAS). The differential diagnosis of Cushing's disease from EAS in cases of ACTH-dependent Cushing's syndrome is a challenging problem. We report here a case of EAS with an unknown source of ACTH secretion. Extensive imaging procedures, involving computed tomography (neck to pelvis), pituitary magnetic resonance imaging, and whole-body 18F-fluorodeoxyglucose-positron emission tomography, failed to reveal the source of ACTH secretion. Intermittent administration of bromocriptine, a short-acting and nonselective dopamine agonist, has afforded adequate suppression of plasma ACTH and cortisol levels over the long term.

Learning points

  • Tumor excision is the primary treatment for EAS. However, when surgery is impossible, medical therapy is needed to treat hypercortisolism.

  • In cases where the source of ACTH secretion is unknown, inhibitors of steroidogenesis, such as metyrapone, mitotane, ketoconazole, and etomidate, are mostly used to suppress cortisol secretion.

  • Medications that suppress ACTH secretion are less effective, therefore less popular, as standard treatments.

  • In the present case, short-term treatment with dopamine agonists was effective for the long-term suppression of both ACTH and cortisol levels.

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Anna Casteràs Department of Endocrinology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, Barcelona 08035, Spain

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Jürgen Kratzsch Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany

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Ángel Ferrández Department of Pediatrics, Andrea Prader Centre, Hospital Universitario Miguel Servet, Zaragoza, Spain

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Carles Zafón
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Antonio Carrascosa Department of Pediatrics, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

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Jordi Mesa
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Summary

Isolated GH deficiency type IA (IGHDIA) is an infrequent cause of severe congenital GHD, often managed by pediatric endocrinologists, and hence few cases in adulthood have been reported. Herein, we describe the clinical status of a 56-year-old male with IGHDIA due to a 6.7 kb deletion in GH1 gene that encodes GH, located on chromosome 17. We also describe phenotypic and biochemical parameters, as well as characterization of anti-GH antibodies after a new attempt made to treat with GH. The height of the adult patient was 123 cm. He presented with type 2 diabetes mellitus, dyslipidemia, osteoporosis, and low physical and psychological performance, compatible with GHD symptomatology. Anti-GH antibodies in high titers and with binding activity (>101 IU/ml) were found 50 years after exposure to exogenous GH, and their levels increased significantly (>200 U/ml) after a 3-month course of 0.2 mg/day recombinant human GH (rhGH) treatment. Higher doses of rhGH (1 mg daily) did not overcome the blockade, and no change in undetectable IGF1 levels was observed (<25 ng/ml). IGHDIA patients need lifelong medical surveillance, focusing mainly on metabolic disturbances, bone status, cardiovascular disease, and psychological support. Multifactorial conventional therapy focusing on each issue is recommended, as anti-GH antibodies may inactivate specific treatment with exogenous GH. After consideration of potential adverse effects, rhIGF1 treatment, even theoretically indicated, has not been considered in our patient yet.

Learning points

  • Severe isolated GHD may be caused by mutations in GH1 gene, mainly a 6.7 kb deletion.

  • Appearance of neutralizing anti-GH antibodies upon recombinant GH treatment is a characteristic feature of IGHDIA.

  • Recombinant human IGF1 treatment has been tested in children with IGHDIA with variable results in height and secondary adverse effects, but any occurrence in adult patients has not been reported yet.

  • Metabolic disturbances (diabetes and hyperlipidemia) and osteoporosis should be monitored and properly treated to minimize cardiovascular disease and fracture risk.

  • Cerebral magnetic resonance imaging should be repeated in adulthood to detect morphological abnormalities that may have developed with time, as well as pituitary hormones periodically assessed.

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