Ahmad Noman, Abosoudah Ibraheem Faisal, Sobaihi Mrouge Mohamed, Algiraigri Ali Hassan, Roujouleh Farh, Ghurab Fatima, Chanoine Jean-Pierre
Consultant Pediatric Endocrinology, King Faisal Specialist Hospital and Research Center , Jeddah , Saudi Arabia.
Consultant Pediatric Oncology, King Faisal Specialist Hospital and Research Center , Jeddah , Saudi Arabia.
Pediatr Hematol Oncol. 2019 Oct;36(7):422-431. doi: 10.1080/08880018.2019.1652710. Epub 2019 Aug 20.
Children with acute lymphocytic leukemia (ALL) are enrolled in advanced treatment protocols involving high doses of glucocorticoids (GCs). Current protocols do not advocate tapering of GCs doses postinduction phase. Prolonged administration of supra-physiologic doses of GCs can induce transient suppression of the hypothalamic pituitary adrenal axis (HPA). Timely recognition of adrenal insufficiency is important in order to ensure that children at risk receive the necessary treatment and follow-up including stress coverage during illness and surgical procedures. 21 newly diagnosed patients with ALL aged 3-10 years old were prospectively enrolled in the study over a 2-year period. All enrolled patients received high doses of GCs as part of a chemotherapy treatment protocol. The HPA axis was assessed prior to the induction phase of chemotherapy and 1-2 weeks after un-tapered discontinuation of GCs. All children had normal HPA axis at baseline. Postinduction 1 mcg ACTH stimulation test result was normal (cortisol > 500 nmol/L) in 75% of children and partially responsive in 25% (cortisol 300-500 nmol/L). None of the participants demonstrated clinically significant adrenal insufficiency following abrupt cessation of GCs. All children in our cohort had either normal or subnormal cortisol response during a low dose ACTH stimulation test 1 to 2 weeks following abrupt discontinuation of GCs, suggesting that any inhibition of the HPA axis is of short duration. We suggest that future studies investigate the timing of adrenal function recovery following GC discontinuation as well as whether tapering of the GC should be recommended.
患有急性淋巴细胞白血病(ALL)的儿童会参与涉及高剂量糖皮质激素(GCs)的先进治疗方案。当前方案不主张在诱导期后逐渐减少GCs剂量。超生理剂量的GCs长期给药可导致下丘脑 - 垂体 - 肾上腺轴(HPA)的短暂抑制。及时识别肾上腺功能不全很重要,以确保有风险的儿童接受必要的治疗和随访,包括在患病和手术过程中的应激处理。在两年期间,前瞻性纳入了21名新诊断的3至10岁ALL患者。所有纳入患者均接受高剂量GCs作为化疗治疗方案的一部分。在化疗诱导期之前以及未逐渐减量停用GCs后1 - 2周评估HPA轴。所有儿童在基线时HPA轴均正常。诱导后,75%的儿童1μg促肾上腺皮质激素(ACTH)刺激试验结果正常(皮质醇>500nmol/L),25%部分反应(皮质醇300 - 500nmol/L)。在突然停用GCs后,没有参与者表现出临床上显著的肾上腺功能不全。在我们队列中的所有儿童在突然停用GCs后1至2周的低剂量ACTH刺激试验期间,皮质醇反应要么正常要么低于正常,这表明对HPA轴的任何抑制都是短暂的。我们建议未来的研究调查停用GCs后肾上腺功能恢复的时间以及是否应推荐逐渐减少GCs剂量。