Einaudi Silvia, Bertorello Nicoletta, Masera Nicoletta, Farinasso Loredana, Barisone Elena, Rizzari Carmelo, Corrias Andrea, Villa Alessia, Riva Francesca, Saracco Paola, Pastore Guido
Department of Pediatric Endocrinology, Regina Margherita Children's Hospital, Turin, Italy.
Pediatr Blood Cancer. 2008 Mar;50(3):537-41. doi: 10.1002/pbc.21339.
A 4-week course of high-dose glucocorticoids may cause prolonged adrenal suppression even after a 9-day tapering phase. In this study, adrenal function and signs and symptoms of adrenal insufficiency were prospectively assessed in children with acute lymphoblastic leukemia (ALL) after induction treatment including high-dose prednisone (PDN) or dexamethasone (DXM).
Sixty-four children with ALL, treated according to the AIEOP ALL 2000 Study protocol, underwent low dose ACTH (LD-ACTH) stimulation 24 hr after the last tapered steroid dose. In those with impaired cortisol response, additional LD ACTH tests were performed every 1-2 weeks until cortisol levels normalized. Signs and symptoms of adrenal insufficiency were recorded during the observation period.
All patients had normal basal cortisol values at diagnosis. Twenty-four hours after last glucocorticoid dose, morning cortisol was reduced in 40/64 (62.5%) patients. LD-ACTH testing showed adrenal suppression in 52/64 (81.5%) patients. At the following ACTH test 7-14 days later, morning cortisol values were reduced in 8/52 (15.4%) patients and response to the test was impaired in 12/52 (23%). Adrenal function completely recovered in all patients within 10 weeks. No difference was found between patients treated with PDN or DXM. Almost 35% of children with impaired cortisol values at the first test developed signs or symptoms of adrenal insufficiency. One child developed a severe adrenal crisis during adrenal suppression.
High-dose glucocorticoid therapy in ALL children may cause prolonged adrenal suppression and related clinical symptoms. Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated.
即使经过9天的减量阶段，为期4周的大剂量糖皮质激素疗程仍可能导致肾上腺抑制延长。在本研究中，对接受包括大剂量泼尼松（PDN）或地塞米松（DXM）在内的诱导治疗后的急性淋巴细胞白血病（ALL）患儿的肾上腺功能以及肾上腺功能不全的体征和症状进行了前瞻性评估。
64例按照AIEOP ALL 2000研究方案治疗的ALL患儿，在最后一次减量类固醇剂量后24小时接受低剂量促肾上腺皮质激素（LD-ACTH）刺激试验。对于皮质醇反应受损的患儿，每1 - 2周进行一次额外的LD ACTH试验，直至皮质醇水平恢复正常。在观察期内记录肾上腺功能不全的体征和症状。
所有患者在诊断时基础皮质醇值均正常。最后一次糖皮质激素剂量后24小时，40/64（62.5%）的患者早晨皮质醇水平降低。LD-ACTH试验显示52/64（81.5%）的患者存在肾上腺抑制。在7 - 14天后的下一次ACTH试验中，8/52（15.4%）的患者早晨皮质醇值降低，12/52（23%）的患者试验反应受损。所有患者的肾上腺功能在10周内完全恢复。接受PDN或DXM治疗的患者之间未发现差异。第一次试验时皮质醇值受损的儿童中，近35%出现了肾上腺功能不全的体征或症状。1名儿童在肾上腺抑制期间发生了严重的肾上腺危象。
ALL患儿的大剂量糖皮质激素治疗可能导致肾上腺抑制延长及相关临床症状。可能需要在应激期间对皮质醇水平进行实验室监测并给予类固醇覆盖治疗。
