ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Cochrane Database Syst Rev. 2017; 11:CD008727

Glucocorticoids (GCs), such as prednisone (prednisolone) or dexamethasone, are essential agents in the treatment of acute lymphoblastic leukemia (ALL), the most common malignancy in childhood. They are administered in highly supraphysiologic doses in cyclic courses. Thus, every pediatric endocrinologist fears HPA axis suppression with consequent cortisol deficiency and higher susceptibility for infections in these patients. However, it is unclear, how often adrenal insufficiency occurs, for how long, and whether it is associated with increased infection. To answer these questions, a Cochrane data analysis was performed, but found only 10 valid studies, which could not be pooled. It is clear that GC therapy for ALL leads to transient adrenal insufficiency (AI), but most children recover within a few to 34 weeks. Interestingly, 2 RCTs found no difference with regard to AI frequency and duration between prednisone and dexamethasone treatments, but in one observational study recovery from AI was faster in prednisone treated individuals compared to dexamethasone, which is maybe the most potent and long-acting corticosteroid in clinical use. Fluconazole treatment (an antifungal drug and CYP inhibitor) prolonged AI. Data on risk association of high-dose GCs with infections in ALL are ambiguous. Therefore, further studies are needed to formulate guidelines for GC replacement therapy and characterize the relationship between GC therapy and infections in ALL.