title: Hypothalamic-pituitary-adrenal function following cranial irradiation.
abstract: We assessed the effect of cranial irradiation on hypothalamic-pituitary (HP)-adrenal function in 17 patients (12 females, 5 males) treated with cranial/ craniospinal irradiation for acute leukemia (2 patients) or tumors distant from the hypothalamus and pituitary (8 medulloblastoma, 3 astrocytoma, 3 rhabdomyosarcoma, 1 ependymoma). Estimated doses of radiation (RT) to the HP region ranged from 18 to 72 Gy. Thirteen of seventeen patients were also treated with chemotherapy. Patients were a median of 3.75 years of age (1.5-19 years) at diagnosis and were studied at a median of 5 years (0.1-20 years) after RT. Patients received corticotropin-releasing factor (oCRF, 1 microgram/kg i.v.), and sampling for cortisol and ACTH levels was performed at -15, 0, 15, 30, 60, 90 and 120 min. The-5- and 0-min levels were combined for a standardized baseline value (Base). Cortisol levels at 0, Base, 30 and 120 min, as well as the peak cortisol response, were significantly lower in the patients. Twelve of seventeen patients' peak cortisol levels fell below the normal range. The patients' mean integrated values for cortisol (area under the curve) were not, however, different from controls. The ACTH responses to oCRF did not differ between patients and controls. No relationship was observed between ACTH or cortisol responses and the time elapsed from treatment or dose of HP RT. Further, in 10 of 12 patients, 0-min dehydroepiandrosterone sulfate levels were lower than the expected normal mean levels for age, sex and pubertal status, and in 4 of these 10 patients the values were below the normal range. These data suggest that some patients treated with HP RT may be at risk for adrenal insufficiency.
authors.affiliation: Department of Pediatrics, New York University Medical Center, NY 10016, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Oberfield
authors.forename: A
authors.initials: A
authors.lastname: Nirenberg
authors.forename: J C
authors.initials: JC
authors.lastname: Allen
authors.forename: H
authors.initials: H
authors.lastname: Cohen
authors.forename: B
authors.initials: B
authors.lastname: Donahue
authors.forename: V
authors.initials: V
authors.lastname: Prasad
authors.forename: R
authors.initials: R
authors.lastname: Schiff
authors.forename: S
authors.initials: S
authors.lastname: Pang
authors.forename: F
authors.initials: F
authors.lastname: Ghavimi
authors.forename: R
authors.initials: R
authors.lastname: David
authors.forename: G
authors.initials: G
authors.lastname: Chrousos
authors.forename: C
authors.initials: C
authors.lastname: Sklar
mesh_terms: D000293:Adolescent; D000311:Adrenal Glands / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001932:Brain Neoplasms / Q000503:physiopathology / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D003346:Corticotropin-Releasing Hormone; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D006258:Head and Neck Neoplasms / Q000503:physiopathology / Q000532:radiotherapy; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007031:Hypothalamus / Q000503:physiopathology*; D007223:Infant; D007700:Kinetics; D007938:Leukemia / Q000503:physiopathology / Q000532:radiotherapy; D008297:Male; D010902:Pituitary Gland / Q000503:physiopathology*
chemical_list: D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone