Holterhus Paul-Martin, Kulle Alexandra, Till Anne-Marie, Stille Caroline, Lamprecht Tabea, Vieth Simon, Lauten Melchior
Department of Pediatrics I, Pediatric Endocrinology and Diabetology, University Hospital of Schleswig-Holstein, UKSH, Campus Kiel and Christian Albrechts University, CAU, Kiel, Germany.
Department of Pediatrics, Pediatric Hematology and Oncology, University Hospital of Schleswig-Holstein, UKSH, Campus Lübeck, Germany.
Endocr Connect. 2023 Sep 11;12(10). doi: 10.1530/EC-23-0002. Print 2023 Oct 1.
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.
糖皮质激素是小儿急性淋巴细胞白血病（ALL）治疗的关键要素，会导致肾上腺抑制。我们旨在评估ALL患儿在柏林-法兰克福-明斯特（BFM）诱导治疗期间肾上腺类固醇的差异反应情况。因此，我们对11例ALL患者在诱导治疗前（第0天）以及诱导治疗第1 - 5天、6 - 12天、13 - 26天、27 - 29天、30 - 35天和36 - 40天期间连续留存的多达7份早晨剩余血清样本进行了基于液相色谱串联质谱（LC-MS/MS）的类固醇分析。同时测定了17-羟孕酮（17OHP）、11-脱氧皮质醇（11S）、皮质醇、11-脱氧皮质酮（DOC）、皮质酮和醛固酮。随后，将类固醇浓度按中位数倍数（MOM）进行标准化，以充分考虑小儿年龄和性别的特定参考范围。直至第29天，糖皮质激素治疗使MOM-皮质醇及其前体MOM-11S和MOM-17OHP受到显著抑制（分别为P < 8.06 × 10-10、P < 5.102 × 10-5、P < 0.0076）。在第27 - 29天，4例患者中有1例皮质醇恢复，在第36 - 40天，5例患者中有2例皮质醇恢复。在盐皮质激素中，皮质酮受到显著抑制（P < 3.115 × 10-6）。将第0天与各治疗时间点相比，醛固酮和DOC无显著变化。然而，2例因败血症接受重症监护治疗的ALL患者在此期间MOM-DOC显著降低（P = 0.006436），且与所有其他时间点相比，醛固酮几乎总是最低。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与肾上腺盐皮质激素合成之间存在功能性相互作用。我们的数据应能激发前瞻性研究以评估潜在的临床相关性。
