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Magdalena Lech Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

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Ruvini Ranasinghe Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Royce P Vincent Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

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David R Taylor Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Lea Ghataore Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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James Luxton Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Fannie Lajeunesse-Trempe Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Quebec Heart and Lung Institute, Laval University, Quebec, Canada

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Pia Roser Department of Endocrinology and Diabetes, University Medical Centre Hamburg Eppendorf, Hamburg, Germany

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Eftychia E Drakou Department of Clinical Oncology, Guy's Cancer Centre - Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UK

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Ling Ling Chuah Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Ashley B Grossman Green Templeton College, University of Oxford, Oxford, UK
Barts and the London School of Medicine, Centre for Endocrinology, William Harvey Institute, London, UK
Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK

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Simon J B Aylwin Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK

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Georgios K Dimitriadis Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UK
Obesity, Type 2 Diabetes and Immunometabolism Research Group, School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Course Sciences, King’s College London, London, UK
Division of Reproductive Health, Warwick Medical School, University of Warwick, Coventry, UK

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Introduction

Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex. Whilst surgery is the preferred treatment, adjunctive therapy with mitotane may be offered post-surgically to minimise the risk of recurrence or, in the absence of surgery, to attenuate progression.

Aim

The objective was to evaluate the effects of mitotane treatment on serum protein concentrations in patients treated for ACC with mitotane therapy and compare this to patients with other adrenal neoplasms and a normal pregnant cohort.

Methods

Serum cortisol, thyroid function tests, adrenocorticotrophic hormone (ACTH), cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG), gonadotrophins and androgens were measured on plasma and serum samples. Thirty-five patients with ACC were included, and mitotane levels were noted to be sub-/supra-therapeutic. Data were tested for normality, reported as mean ± s.d., and compared to other two cohorts using paired-sample t-test with a 5% P-value for significance and a 95% CI.

Results

Patients on mitotane therapy had a higher mean serum CBG concentration compared to the adrenal neoplasm group (sub-therapeutic: 79.5 (95% CI: 33.6, 125.4 nmol/L), therapeutic: 85.3 (95% CI: 37.1–133.6 nmol/L), supra-therapeutic: 75.7 (95% CI: −19.3, 170.6 nmol/L) and adrenal neoplasm: 25.5 (95% CI: 17.5, 33.5 nmol/L). Negative correlations between serum cortisol and CBG concentration were demonstrated within the supra-therapeutic plasma mitotane and adrenal neoplasm groups.

Conclusion

Patients with ACC and therapeutic plasma mitotane concentrations had higher serum CBG concentrations compared to those with adrenal neoplasms or pregnant women, and higher serum cortisol. Whilst there was no direct correlation with cortisol and mitotane level, the negative correlation of cortisol with CBG may suggest that the direct effect of mitotane in increasing cortisol may also reflect that mitotane has a direct adrenolytic effect.

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