Adrenal function after induction therapy for acute lymphoblastic leukemia in children short: adrenal function in ALL

Abstract

Prednisolone used in the induction phase of the treatment of acute lymphoblastic leukemia (ALL) may suppress hypothalamic-pituitary-adrenal axis and require hydrocortisone substitution. In this retrospective analysis, we reviewed altogether 371 ACTH stimulation tests of 352 children after a uniform NOPHO (Nordic Society of Pediatric Hematology and Oncology) ALL induction. Both low- and standard-dose ACTH tests were used. Full recovery of adrenal function was defined by both normal basal and stimulated cortisol levels. Sixty-two percent of patients were detected with normal adrenal function in median of 15 days after tapering of prednisolone. Both low basal and stimulated cortisol levels were detected in 13% of patients. The median time to normal adrenal function was 31 days (95% CI 28-34), 24 days (95% CI 18-30), and 12 days (95% CI 10-14) for those with basal cortisol <107, 107-183, and >183 nmol/L at first ACTH testing, respectively. Patients with fluconazole prophylaxis had higher median baseline cortisol levels compared to patients without prophylaxis (207 nmol/L, range 21-839 nmol/L vs. 153 nmol/L, range 22-832 nmol/L, P = 0.003).Conclusion: These data can be used to reduce unnecessary substitution or testing, but also to guarantee hydrocortisone substitution for those at risk. What is Known: •These data can be used to reduce unnecessary hydrocortisone substitution or ACTH testing. •Our data helps to guarantee hydrocortisone substitution for those at risk of adrenal insufficiency. What is New: •Full recovery of adrenal function after ALL induction is detected in 62% of patients already at 15 days after tapering of prednisolone. •Both basal and stimulated cortisol testing are required for detection of full adrenal recovery. •Recovery time of adrenal function is extended over 3-4 weeks after tapering of prednisolone in patients with low basal cortisol levels (<107 nmol/L) at first testing.

Keywords: ACTH testing; Acute lymphoblastic leukemia; Adrenal insufficiency; Prednisolone.

Fig. 1

Consort diagram of study patients for analysis of adrenal recovery after prednisolone induction for acute lymphoblastic leukemia. Patients have been treated on NOPHO (Nordic Society of Pediatric Hematology and Oncology) ALL 92 (N = 139), ALL 2000 (97), and ALL 2008 (80) protocols

Fig. 2

Adrenal function recovery with time (in days). The figure illustrates the variability in time of testing. It also shows the increasing percentage of patients with normal basal cortisol secretion

Fig. 3

Full adrenal recovery time after prednisolone as function of basal cortisol level. Patients were divided into three groups according to the basal cortisol level at first ACTH test after tapering of prednisolone. Basal cortisol groups <107, 107–183, and >183.01 nmol/L are indicated in blue, red, and yellow, respectively