Suppression of adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia in Iran

Shahla Ansari, Marzieh Sabzechian, Azadeh Kiumarsi, Masoudeh Sabzechian, Tahereh Rostami, Farzaneh Rouhani

Abstract


A 4 weeks course of high-dose glucocorticoids (GCs) may cause prolonged adrenal suppression even after a 9 days 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 with high-dose prednisone. In 42 children with newly diagnosed ALL, a baseline serum cortisol level was assessed and after receiving a 28 days of high dose prednisone according to the Berlin-Frankfu¨rt-Mu¨nster 2009 protocol ad a 9 days tapering phase, serum cortisol level was assessed again and those whose serum cortisol level was normal underwent low-dose adrenocorticotropic hormone (LDACTH) stimulation 24 h after the last tapered steroid dose. Signs and symptoms of adrenal insufficiency were recorded during the observation period. All patients except one who was excluded had normal basal cortisol values at diagnosis. Twenty-four hours after last GC dose, morning cortisol was reduced in 15 (36.5%) patients. LDACTH testing showed adrenal suppression in 17 (41.4%) patients. High-dose GC therapy in ALL children may cause adrenal suppression even after a tapering phase. Laboratory monitoring of cortisol levels and steroid coverage during stress episodes may be indicated.


Keywords


Adrenal axis function, Steroid therapy, Acute lymphoblastic leukemia

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References


McNeer JL, Nachman JB. The optimal use of steroids in paediatric acute lymphoblastic leukaemia: no easy answers. Br J Haematol. 2010;149:638-52.

Migeon CJ, Lanes RL. Adrenal cortex. Hypo and hyperfunction. In: Lipfitz F, editor. Pediatric Endocrinology. New York: Marcel Dekker Inc.; 1996: 321-45.

Krasner AS. Glucocorticoid-induced adrenal insufficiency. JAMA. 1999;282(7):671-6.

Miller WL. The adrenal cortex and its disorders. In: Brook CGS, Hindmarsch PC, editors. Clinical Pediatric Endocrinology. Oxford: Blackwell Science; 2001: 321-78.

Tyrrel JB, Baxter JD. Glucocorticoid therapy. In: Felig P, Baxter JD, Broadus AE, Frohman LA, editors. Endocrinology and Metabolism. New York: McGraw Hill; 1981: 788-817.

Zora JA, Zimmerman D, Carey TL, O’Connell EJ, Yunginger JW. Hypothalamic-pituitary-adrenal axis suppression after short-term, high-dose glucocorticoid therapy in children with asthma. J Allergy Clin Immunol. 1986;77:9-13.

Lamberts SWJ, Bruining HA, de Jong FH. Corticosteroid therapy in severe illness. N Engl J Med. 1968;278:405-9.

Fraser CG, Preuss FS, Bigford WD. Adrenal atrophy and irreversible shock associated with cortisone therapy. J Am Med Assoc. 1952;149(17):1542-3.

Agwu JC, Spoudeas H, Hindmarsh PC, Pringle PJ, Brook CG. Tests of adrenal insufficiency. Arch Dis Child. 1999;80(4):330-3.

Dixon RB, Christy NP. On the various forms of corticosteroid withdrawal syndrome. Am J Med. 1980;68(2):224-30.

Papanicolaou DA, Tsigos C, Oldfield EH, Chrousos GP. Acute glucocorticoid deficiency is associated with plasma elevations of interleukin-6: does the latter participate in the symptomatology of the steroid withdrawal syndrome and adrenal insufficiency? J Clin Endocrinol Metab. 1996;81(6):2303-6.

Hochberg Z, Pacak K, Chrousos GP. Endocrine withdrawal syndromes. Endocr Rev. 2003;24(4):523 38.

Wheeler K, Chessells JM, Bailey CC, Richards SM. Treatment related deaths during induction and in first remission in acute lymphoblastic leukaemia: MRC UKALL X. Arch Dis Child. 1996;74(2):101-7.

Schrappe M, Camitta B, Pui CH, Eden T, Gaynon P, Gustafsson G, et al. Long-term results of large prospective trials in childhood acute lymphoblastic leukemia. Leukemia. 2000;14(12):2193-4.

Conter V, Aricò M, Valsecchi MG, Basso G, Biondi A, Madon E, et al. Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) acute lymphoblastic leukemia studies, 1982-1995. Leukemia. 2000;14(12):2196 204.

Margolin L, Cope DK, Bakst-Sisser R, Greenspan J. The steroid withdrawal syndrome: a review of the implications, etiology, and treatments. J Pain Symptom Manage. 2007;33(2):224-8.

Saracco P, Bertorello N, Farinasso L, Einaudi S, Barisone E, Altare F, et al. Steroid withdrawal syndrome during steroid tapering in childhood acute lymphoblastic leukemia: a controlled study comparing prednisone versus dexamethasone in induction phase. J Pediatr Hematol Oncol. 2005;27(3):141-4.

Albert SG, DeLeon MJ, Silverberg AB. Possible association between high-dose fluconazole and adrenal insufficiency in critically ill patients. Crit Care Med. 2001;29(3):668-70.

Shibata S, Kami M, Kanda Y, Machida U, Iwata H, Kishi Y, et al. Acute adrenal failure associated with fluconazole after administration of high-dose cyclophosphamide. Am J Hematol. 2001;66(4):303 5.

Einaudi S, Bertorello N, Masera N, Farinasso L, Barisone E, Rizzari C, et al. Adrenal axis function after high-dose steroid therapy for childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2008;50(3):537-41.

Gordijn MS, Gemke RJ, van Dalen EC, Rotteveel J, Kaspers GJ. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia. Cochrane Database Syst Rev. 2012;5:CD008727.

Spiegel RJ, Vigersky RA, Oliff AI, Echelberger CK, Bruton J, Poplack DG. Adrenal suppression after short-term corticosteroid therapy. Lancet. 1979;1(8117):630-3.

Lightner ES, Johnson H, Corrigan JJ Jr. Rapid adrenocortical recovery after short-term glucocorticoid therapy. Am J Dis Child. 1981;135(9):790-2.

Cunha Cde F, Silva IN, Finch FL. Early adrenocortical recovery after glucocorticoid therapy in children with leukemia. J Clin Endocrinol Metab. 2004;89(6):2797 802.

Felner EI, Thompson MT, Ratliff AF, White PC, Dickson BA. Time course of recovery of adrenal function in children treated for leukemia. J Pediatr. 2000;137(1):21-4.

Kuperman H, Damiani D, Chrousos GP, Dichtchekenian V, Manna TD, Filho VO, et al. Evaluation of the hypothalamic-pituitary-adrenal axis in children with leukemia before and after 6 weeks of high-dose glucocorticoid therapy. J Clin Endocrinol Metab. 2001;86(7):2993-6.

Petersen KB, Müller J, Rasmussen M, Schmiegelow K. Impaired adrenal function after glucocorticoid therapy in children with acute lymphoblastic leukemia. Med Pediatr Oncol. 2003;41:110-4.

Rix M, Birkebaek NH, Rosthøj S, Clausen N. Clinical impact of corticosteroid-induced adrenal suppression during treatment for acute lymphoblastic leukemia in children: a prospective observational study using the low-dose adrenocorticotropin test. J Pediatr. 2005;147(5):645-50.