PDF(Pubmed)
Abstract：
Glucocorticoids represent a key element in the treatment of pediatric acute lymphoblastic leukemia (ALL) and lead to adrenal suppression. We aimed to assess the differential response profile of adrenal steroids in children with ALL during BFM (Berlin-Frankfurt-Münster) induction treatment. Therefore, we performed liquid chromatography tandem-mass spectrometry (LC-MS/MS)-based steroid profiling of up to seven consecutive leftover morning serum samples derived from 11 patients (pts) with ALL before (day 0) and during induction therapy at days 1-5, 6-12, 13-26, 27-29, 30-35 and 36-40. 17-hydroxyprogesterone (17OHP), 11-deoxycortisol (11S), cortisol, 11-deoxycorticosterone (DOC), corticosterone and aldosterone were determined in parallel. Subsequently, steroid concentrations were normalized by multiples of median (MOM) to adequately consider pediatric age- and sex-specific reference ranges. MOM-cortisol and its precursors MOM-11S and MOM-17OHP were significantly suppressed by glucocorticoid treatment until day 29 (P < 8.06 × 10-10, P < 5.102 × 10-5, P < 0.0076, respectively). Cortisol recovered in one of four pts at days 27-29 and in two of five pts at days 36-40. Among the mineralocorticoids, corticosterone was significantly suppressed (P < 3.115 × 10-6). Aldosterone and DOC showed no significant changes when comparing day 0 to the treatment time points. However, two ALL patients with ICU treatment due to the sepsis showed significantly lower MOM-DOC (P = 0.006436) during that time and almost always the lowest aldosterone compared to all other time points. Suppression of mineralocorticoid precursors under high-dose glucocorticoid therapy suggests a functional cross talk of central glucocorticoid regulation and adrenal mineralocorticoid synthesis. Our data should stimulate prospective investigation to assess potential clinical relevance.
摘要：
糖皮质激素是治疗小儿急性淋巴细胞白血病（ALL）的关键因素，并导致肾上腺抑制。我们旨在评估BFM（柏林-法兰克福-明斯特）诱导治疗期间ALL儿童肾上腺类固醇的差异反应特征。因此,在第1-5,6-12,13-26,27-29,30-35和36-40天,我们对11例ALL患者(pts)在诱导治疗前(第0天)和诱导治疗期间的7份连续剩余晨间血清样本进行了基于LC-MS/MS的类固醇分析.17-羟基孕酮（17OHP），11-脱氧皮质醇（11S），皮质醇,11-脱氧皮质酮（DOC），同时测定皮质酮和醛固酮。随后，通过中位数倍数(MOM)对类固醇浓度进行归一化,以充分考虑儿科年龄和性别特异性参考范围.MOM-皮质醇及其前体MOM-11S和MOM-17OHP被糖皮质激素治疗显著抑制直到第29天(分别为p<8.06x10-10,p<5.102x10-5,p<0.0076)。皮质醇在第27-29天4分中的1分和第36-40天5分中的2分中恢复。在盐皮质激素中，皮质酮被显著抑制(p<3.115x10-6)。当比较第0天与治疗时间点时,醛固酮和DOC没有显示出显著变化。然而,与所有其他时间点相比，2例由于败血症而接受ICU治疗的ALL患者在此期间显示出显着较低的MOM-DOC（p=0.006436），并且几乎总是最低的醛固酮。高剂量糖皮质激素治疗下盐皮质激素前体的抑制表明中枢糖皮质激素调节和肾上腺盐皮质激素合成的功能性串扰。我们的数据应激发前瞻性调查以评估潜在的临床相关性。
