Evaluation of the hypothalamic-pituitary-adrenal axis in children with leukemia before and after 6 weeks of high-dose glucocorticoid therapy

Among the adverse effects arising from chronic high-dose glucocorticoid tre atment, adrenal insufficiency secondary to suppression of the hypothalamic- pituitary-adrenal (HPA) axis is a cause for concern. Glucocorticoid-induced adrenal suppression is related to the duration of therapy, type of steroid used and dosage, and schedule of glucocorticoid administration. To evaluat e the suppression and recovery time of the HPA axis in children with acute leukemia, we performed the ovine CRH (oCRH) stimulation test in 15 patients , who were given high doses of dexamethasone as part of their induction che motherapy for 42 days. The oCRH tests were performed before, and 7 and 14 d ays after, discontinuation of the glucocorticoid. The ACTH levels were not significantly different among the 3 tests. The cortisol levels, however, we re significantly (albeit mildly) lower, both basally and after oCRH, 1 and 2 weeks post treatment than before therapy. Six patients had cortisol value s that remained suppressed 2 weeks after discontinuation of therapy. One of these patients had manifestations of mild adrenal insufficiency, 6-8 days after discontinuation of therapy, but required no glucocorticoid coverage. We conclude that up to 2 weeks after discontinuation of 6 weeks of high-dos e dexamethasone administration, the HPA axis of patients with acute leukemi a is mildly suppressed but infrequently associated with clinical manifestat ions of adrenal insufficiency. This may indicate that major stress, when co ncurrent with glucocorticoid treatment, may prevent clinically significant adrenal suppression.