دورية أكاديمية
Recovery of adrenal function after stopping mitotane in patients with adrenocortical carcinoma.
| العنوان: | Recovery of adrenal function after stopping mitotane in patients with adrenocortical carcinoma. |
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| المؤلفون: | Altieri B; Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Oberduerrbacher Strasse 6, 97080 Würzburg, Germany., Kimpel O; Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Oberduerrbacher Strasse 6, 97080 Würzburg, Germany., Megerle F; Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Oberduerrbacher Strasse 6, 97080 Würzburg, Germany., Detomas M; Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Oberduerrbacher Strasse 6, 97080 Würzburg, Germany., Chifu I; Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Oberduerrbacher Strasse 6, 97080 Würzburg, Germany., Fuss CT; Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Oberduerrbacher Strasse 6, 97080 Würzburg, Germany., Quinkler M; Endocrinology in Charlottenburg, Stuttgarter Platz 1, 10627 Berlin, Germany., Kroiss M; Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Oberduerrbacher Strasse 6, 97080 Würzburg, Germany.; Department of Internal Medicine IV, University Hospital, Ludwig-Maximilians-University Munich, Ziemssenstrasse 1, 80336 Munich, Germany., Fassnacht M; Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Oberduerrbacher Strasse 6, 97080 Würzburg, Germany.; Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Strasse 6, 97080 Würzburg, Germany.; Central Laboratory, University Hospital Würzburg, Oberduerrbacher Strasse 6, 97080 Würzburg, Germany. |
| المصدر: | European journal of endocrinology [Eur J Endocrinol] 2024 Feb 01; Vol. 190 (2), pp. 139-150. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Print Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : Oxford : Oxford University Press Original Publication: Oslo, Norway : Scandinavian University Press, c1994- |
| مواضيع طبية MeSH: | Adrenocortical Carcinoma*/drug therapy , Adrenal Cortex Neoplasms*/pathology , Adrenal Insufficiency*/drug therapy, Humans ; Female ; Mitotane/therapeutic use ; Retrospective Studies ; Hypothalamo-Hypophyseal System ; Antineoplastic Agents, Hormonal/therapeutic use ; Pituitary-Adrenal System |
| مستخلص: | Objective: Mitotane is the standard therapy of adrenocortical carcinoma (ACC) due to its relative selectivity of its cytotoxic effects toward adrenocortical cells. Therefore, it virtually always leads to adrenal insufficiency. Frequency and characteristics of hypothalamic-pituitary-adrenal axis recovery after discontinuation are ill-defined. Methods: This was a retrospective study of patients with ACC adjuvantly treated with mitotane for ≥12 months who were disease-free at mitotane stop and had a minimum follow-up ≥1 year. Primary endpoint was adrenal recovery. Cox regression analyses were used to identify predictive factors. Moreover, mitotane plasma elimination rate and hormonal changes after mitotane stop were investigated. Results: Fifty-six patients (36 women) treated with mitotane for a median time of 25 months and an average daily dose of 2.8 g were included. Median time after discontinuation until mitotane levels dropped below 5 and 2 mg/L, and the detection limit was 152 days (interquartile range: 114-202), 280 days (192-370), and 395 days (227-546), respectively. Full adrenal recovery was documented in 32 (57%) patients after a median time of 26 months (95% confidence interval [CI] = 19.6-32.4). In 4 patients (7.1%), adrenal insufficiency persisted >5 years after discontinuation. Mitotane peak ≥ 27 mg/L significantly correlated with longer time to adrenal recovery (hazard ratio [HR] = 0.2, 95% CI = 0.1-0.8, P = .03). Twenty-seven of 38 patients (71%) followed in reference centers achieved adrenal recovery compared with only 5/18 (28%) followed up in non-reference centers (HR = 4.51, 95% CI = 1.71-11.89, P = .002). Other investigated factors were not associated with adrenal function after discontinuation. Conclusions: Our study demonstrates that adrenal recovery occurs in most patients after stopping mitotane, particularly when followed up in specialized centers, but not in all. Elimination time of mitotane after treatment discontinuation is very long but individually quite variable. Competing Interests: Conflict of interest: O.K. received speaker honoraria from HRA Pharma. The other authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.) |
| معلومات مُعتمدة: | 314061271 German Research Foundation; Clinician Scientist; Else Kröner-Fresenius-Stiftung; Eva Luise und Horst Köhler Stiftung |
| فهرسة مساهمة: | Keywords: ACTH; HPA axis; adrenal insufficiency; drug exposure; mitotane discontinuation |
| المشرفين على المادة: | 78E4J5IB5J (Mitotane) 0 (Antineoplastic Agents, Hormonal) |
| تواريخ الأحداث: | Date Created: 20240120 Date Completed: 20240208 Latest Revision: 20240208 |
| رمز التحديث: | 20240208 |
| DOI: | 10.1093/ejendo/lvae007 |
| PMID: | 38244214 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1479-683X |
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| DOI: | 10.1093/ejendo/lvae007 |