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

• Published in: The journal of clinical endocrinology and metabolism Vol. 86; no. 7; pp. 2993 - 2996
• Main Authors: KUPERMAN, Hilton, DAMIANI, Durval, CHROUSOS, George P, DICHTCHEKENIAN, Vaê, DELLA MANNA, Thais, ODONE, Vicente FILHO, SETIAN, Nuvarte
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.07.2001
• Subjects: Adrenal Glands - drug effects; Adrenal Glands - physiopathology; Adrenal Insufficiency - chemically induced; Adrenocorticotropic Hormone - blood; Biological and medical sciences; Child; Child, Preschool; Corticotropin-Releasing Hormone; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Dexamethasone - therapeutic use; Drug toxicity and drugs side effects treatment; Female; Glucocorticoids - administration & dosage; Glucocorticoids - adverse effects; Glucocorticoids - therapeutic use; Humans; Hydrocortisone - blood; Hypothalamus - drug effects; Hypothalamus - physiopathology; Infant; Kinetics; Male; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Pituitary Gland - drug effects; Pituitary Gland - physiopathology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - physiopathology; Endocrinopathy; Human; Corticosteroid; Hypothalamohypophysoadrenal axis disorders; Dexamethasone; Toxicity; Acute; Infant; Malignant hemopathy; Chronic lymphocytic leukemia; Adrenal insufficiency; Lymphoproliferative syndrome; Adrenal gland diseases; Hormonal investigation; High dose; Child
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.86.7.2993

Among the adverse effects arising from chronic high-dose glucocorticoid treatment, 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 evaluate 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 chemotherapy for 42 days. The oCRH tests were performed before, and 7 and 14 days after, discontinuation of the glucocorticoid. The ACTH levels were not significantly different among the 3 tests. The cortisol levels, however, were significantly (albeit mildly) lower, both basally and after oCRH, 1 and 2 weeks post treatment than before therapy. Six patients had cortisol values 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-dose dexamethasone administration, the HPA axis of patients with acute leukemia is mildly suppressed but infrequently associated with clinical manifestations of adrenal insufficiency. This may indicate that major stress, when concurrent with glucocorticoid treatment, may prevent clinically significant adrenal suppression.