Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Oberduerrbacher Strasse 6, 97080 Würzburg, Germany.
Endocrinology in Charlottenburg, Stuttgarter Platz 1, 10627 Berlin, Germany.
Eur J Endocrinol. 2024 Feb 1;190(2):139-150. doi: 10.1093/ejendo/lvae007.
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.
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.
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.
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.
米托坦是治疗肾上腺皮质癌（ACC）的标准疗法，因为它对肾上腺皮质细胞的细胞毒性作用具有相对选择性。因此，它几乎总是导致肾上腺功能不全。停药后下丘脑-垂体-肾上腺轴恢复的频率和特征尚未明确。
这是一项回顾性研究，纳入了辅助性接受米托坦治疗≥12 个月且停药时无疾病且随访时间≥1 年的 ACC 患者。主要终点是肾上腺恢复。使用 Cox 回归分析确定预测因素。此外，还研究了米托坦停药后米托坦的血浆消除率和激素变化。
56 例（36 名女性）接受米托坦治疗，中位时间为 25 个月，平均日剂量为 2.8 g。从停药到米托坦水平降至 5 和 2 mg/L 以下且检测下限分别为 152 天（四分位距[IQR]：114-202）、280 天（192-370）和 395 天（227-546）的中位时间。32 例（57%）患者在停药后中位时间 26 个月后（95%置信区间[CI] = 19.6-32.4）完全恢复肾上腺功能。4 例（7.1%）患者停药后肾上腺功能不全持续>5 年。米托坦峰值≥27 mg/L 与恢复肾上腺功能的时间较长显著相关（风险比[HR] = 0.2，95%CI = 0.1-0.8，P =.03）。在参考中心随访的 38 例患者中的 27 例（71%）与在非参考中心随访的 18 例患者中的 5 例（28%）（HR = 4.51，95%CI = 1.71-11.89，P =.002）相比，恢复了肾上腺功能。停药后其他研究因素与肾上腺功能无关。
我们的研究表明，大多数患者在停止米托坦治疗后会恢复肾上腺功能，尤其是在专门的中心随访时，但并非所有患者都能恢复。治疗停止后米托坦的消除时间非常长，但个体差异很大。
Zotero 插件