{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T11:30:43Z","timestamp":1787398243009,"version":"build-2736575974"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["314061271"],"award-info":[{"award-number":["314061271"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinician Scientist"},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007952","name":"Eva Luise und Horst K\u00f6hler Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007952","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>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\u2013pituitary\u2013adrenal axis recovery after discontinuation are ill-defined.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This was a retrospective study of patients with ACC adjuvantly treated with mitotane for \u226512 months who were disease-free at mitotane stop and had a minimum follow-up \u22651 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Fifty-six patients (36 women) treated with mitotane for a median time of 25 months and an average daily dose of 2.8\u2005g were included. Median time after discontinuation until mitotane levels dropped below 5 and 2\u2005mg\/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 &amp;gt;5 years after discontinuation. Mitotane peak \u2265 27\u2005mg\/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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvae007","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T20:36:23Z","timestamp":1705782983000},"page":"139-150","source":"Crossref","is-referenced-by-count":4,"title":["Recovery of adrenal function after stopping mitotane in patients with adrenocortical carcinoma"],"prefix":"10.1093","volume":"190","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2616-3249","authenticated-orcid":false,"given":"Barbara","family":"Altieri","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg , Oberduerrbacher Strasse 6, 97080 W\u00fcrzburg , 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1490-5575","authenticated-orcid":false,"given":"Mario","family":"Detomas","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg , Oberduerrbacher Strasse 6, 97080 W\u00fcrzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6741-2689","authenticated-orcid":false,"given":"Irina","family":"Chifu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg , Oberduerrbacher Strasse 6, 97080 W\u00fcrzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmina Teresa","family":"Fuss","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg , Oberduerrbacher Strasse 6, 97080 W\u00fcrzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4028-1671","authenticated-orcid":false,"given":"Marcus","family":"Quinkler","sequence":"additional","affiliation":[{"name":"Endocrinology in Charlottenburg , Stuttgarter Platz 1, 10627 Berlin , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Kroiss","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg , Oberduerrbacher Strasse 6, 97080 W\u00fcrzburg , Germany"},{"name":"Department of Internal Medicine IV, University Hospital, Ludwig-Maximilians-University Munich , Ziemssenstrasse 1, 80336 Munich , 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