Pulsatile growth hormone secretion in children with acute lymphoblastic leukemia after 1800 cGy cranial radiation

The relationship between intensity of central nervous system preventive therapy and the development of hypothalamic pituitary dysfunction is unclear in patients with acute lymphoblastic leukemia. In a previous report, we demonstrated uniform decreases in spontaneous secretion of growth hormone following 2400 cGy whole brain radiation. In this study, we measured basal growth hormone levels every 20 minutes over 24 hr in five survivors of childhood acute lymphoblastic leukemia treated with 1800 cGy cranial radiation. Four of the patients had been off therapy 2 9/12-4 3/12 years. Growth hormone secretion in these patients, as indicated by mean growth hormone concentration, pulse amplitude and frequency, was clearly greater than that seen following 2400 cGy and appeared to be normal compared with sex- and Tanner stage-matched literature controls. However, serial growth measurements showed significant decreases in height percentiles in two of these children. The fifth patient, who had already approached her adult height at the time of diagnosis, had been off therapy only 1 year and had a mean growth hormone level intermediate between those of normal controls and previously reported children treated with 2400 cGy. These data suggest (a) that the effect of radiation therapy on spontaneous pulsatile growth hormone secretion may be dose related, and (b) that short stature in a given patient may not be indicative of subnormal basal growth hormone levels. Further longitudinal investigation may clarify whether early transient changes in GH secretion occur that may normalize over time.