Adrenal function following acute discontinuation of glucocorticoids in children with acute lymphocytic leukemia: A prospective study

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords:

• Hypothalamic pituitary adrenal axis
• glucocorticoids
• acute lymphocytic leukemia

Acknowledgement

The authors are thankful to Ms Emily Heaphy for her contribution in statistical analysis and manuscript editing.

Disclosure statement

The authors declare that they have no conflict of interest nor received any financial support for this study.