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The impact of mitotane therapy on serum-free proteins in patients with adrenocortical carcinoma
Endocrine Connections ( IF 2.9 ) Pub Date : 2024-03-01 , DOI: 10.1530/ec-23-0159
Magdalena Lech 1 , Ruvini Ranasinghe 2 , Royce P Vincent 3 , David R Taylor 4 , Lea Ghataore 5 , James Luxton 6 , Fannie Lajeunesse-Trempe 7 , Pia Roser 8 , Eftychia E Drakou 9 , Ling Ling Chuah 10 , Ashley B Grossman 11 , Simon Jb Aylwin 12 , Georgios K Dimitriadis 13
Affiliation  

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.



中文翻译:

米托坦治疗对肾上腺皮质癌患者血清游离蛋白的影响

简介: 肾上腺皮质癌(ACC)是一种罕见的肾上腺皮质恶性肿瘤。虽然手术是首选治疗方法,但可以在手术后提供米托坦辅助治疗,以最大限度地降低复发风险,或者在不进行手术的情况下减缓进展。

目的:评估米托坦治疗对接受米托坦治疗的 ACC 患者血清蛋白浓度的影响,并将其与其他肾上腺肿瘤患者和正常妊娠队列进行比较。

方法:对血浆和血清样本进行血清皮质醇、甲状腺功能检查、促肾上腺皮质激素(ACTH)、皮质醇结合球蛋白(CBG)、甲状腺素结合球蛋白(TBG)、促性腺激素和雄激素的检测。包括 35 名 ACC 患者,米托坦水平低于/高于/治疗水平。数据进行正态性测试,报告为平均值±SD,并使用配对样本 t 检验与其他两个队列进行比较,显着性 p 值为 5%,置信区间 (CI) 为 95%。

结果:与肾上腺肿瘤组相比,接受米托坦治疗的患者平均血清 CBG 浓度较高(亚治疗:79.5(95% CI:33.6,125.4nmol/L),治疗:85.3(95% CI:37.1-133.6nmol/L) L),超治疗:75.7 (95% CI: -19.3,170.6nmol/L):肾上腺肿瘤 25.5 (95% CI:17.5,33.5nmol/L)。结论:与肾上腺肿瘤组或孕妇相比,ACC 和血浆米托坦治疗浓度患者的血清 CBG 浓度较高,血清皮质醇也较高。米托坦水平,皮质醇与CBG的负相关可能表明米托坦增加皮质醇的直接作用也可能反映了米托坦具有直接的肾上腺素分解作用。

更新日期:2024-02-12
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