Adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia.
BACKGROUND
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Einaudi
Silvia
S
Department of Pediatric Endocrinology, Regina Margherita Children's Hospital, Turin, Italy. silvein@libero.it
Bertorello
Nicoletta
N
Masera
Nicoletta
N
Farinasso
Loredana
L
Barisone
Elena
E
Rizzari
Carmelo
C
Corrias
Andrea
A
Villa
Alessia
A
Riva
Francesca
F
Saracco
Paola
P
Pastore
Guido
G
D000302:Adrenal Cortex / Q000187:drug effects; D000309:Adrenal Insufficiency / Q000139:chemically induced* / Q000188:drug therapy; D000324:Adrenocorticotropic Hormone; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000503:physiopathology; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000503:physiopathology*