The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinoma
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 o...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Bioscientifica
2024-02-01
|
| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | https://ec.bioscientifica.com/view/journals/ec/aop/ec-23-0159/ec-23-0159.xml |
| _version_ | 1797317354307190784 |
|---|---|
| author | Magdalena Lech Ruvini Ranasinghe Royce P Vincent David R Taylor Lea Ghataore James Luxton Fannie Lajeunesse-Trempe Pia Roser Eftychia E Drakou Ling Ling Chuah Ashley B Grossman Simon J B Aylwin Georgios K Dimitriadis |
| author_facet | Magdalena Lech Ruvini Ranasinghe Royce P Vincent David R Taylor Lea Ghataore James Luxton Fannie Lajeunesse-Trempe Pia Roser Eftychia E Drakou Ling Ling Chuah Ashley B Grossman Simon J B Aylwin Georgios K Dimitriadis |
| author_sort | Magdalena Lech |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T03:33:42Z |
| format | Article |
| id | doaj.art-ec0eb90608324425b574464973b34ee4 |
| institution | Directory Open Access Journal |
| issn | 2049-3614 |
| language | English |
| last_indexed | 2024-03-08T03:33:42Z |
| publishDate | 2024-02-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-ec0eb90608324425b574464973b34ee42024-02-10T13:25:29ZengBioscientificaEndocrine Connections2049-36142024-02-01133110https://doi.org/10.1530/EC-23-0159The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinomaMagdalena Lech0Ruvini Ranasinghe1Royce P Vincent2David R Taylor3Lea Ghataore4James Luxton5Fannie Lajeunesse-Trempe6Pia Roser7Eftychia E Drakou8Ling Ling Chuah9Ashley B Grossman10Simon J B Aylwin11Georgios K Dimitriadis12Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UKDepartment of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UKDepartment 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 Department of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UKDepartment of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UKDepartment of Clinical Biochemistry, King’s College Hospital NHS Foundation Trust, Denmark Hill, London, UKDepartment 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 Department of Endocrinology and Diabetes, University Medical Centre Hamburg Eppendorf, Hamburg, GermanyDepartment of Clinical Oncology, Guy's Cancer Centre - Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UKDepartment of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UKGreen 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 Department of Endocrinology ASO/EASO COM, King's College Hospital NHS Foundation Trust, Denmark Hill, London, UKDepartment 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 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.https://ec.bioscientifica.com/view/journals/ec/aop/ec-23-0159/ec-23-0159.xmlmitotaneadrenocortical carcinomaserum-free proteinscortisol-binding globulinthyroid-binding globulin |
| spellingShingle | Magdalena Lech Ruvini Ranasinghe Royce P Vincent David R Taylor Lea Ghataore James Luxton Fannie Lajeunesse-Trempe Pia Roser Eftychia E Drakou Ling Ling Chuah Ashley B Grossman Simon J B Aylwin Georgios K Dimitriadis The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinoma Endocrine Connections mitotane adrenocortical carcinoma serum-free proteins cortisol-binding globulin thyroid-binding globulin |
| title | The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinoma |
| title_full | The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinoma |
| title_fullStr | The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinoma |
| title_full_unstemmed | The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinoma |
| title_short | The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinoma |
| title_sort | impact of mitotane therapy on serum free proteins in patients with adrenocortical carcinoma |
| topic | mitotane adrenocortical carcinoma serum-free proteins cortisol-binding globulin thyroid-binding globulin |
| url | https://ec.bioscientifica.com/view/journals/ec/aop/ec-23-0159/ec-23-0159.xml |
| work_keys_str_mv | AT magdalenalech theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT ruviniranasinghe theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT roycepvincent theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT davidrtaylor theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT leaghataore theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT jamesluxton theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT fannielajeunessetrempe theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT piaroser theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT eftychiaedrakou theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT linglingchuah theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT ashleybgrossman theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT simonjbaylwin theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT georgioskdimitriadis theimpactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT magdalenalech impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT ruviniranasinghe impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT roycepvincent impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT davidrtaylor impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT leaghataore impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT jamesluxton impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT fannielajeunessetrempe impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT piaroser impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT eftychiaedrakou impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT linglingchuah impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT ashleybgrossman impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT simonjbaylwin impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma AT georgioskdimitriadis impactofmitotanetherapyonserumfreeproteinsinpatientswithadrenocorticalcarcinoma |