Effects of low-dose cranial radiation on growth hormone secretory dynamics and hypothalamic-pituitary function
G. Costin
Division of Endocrinology and Metabolism, Childrens Hospital, Los Angeles, CA 90027.
Spontaneous growth hormone (GH) secretory dynamics and
hypothalamic-pituitary function were studied in 16 long-term survivors of
acute lymphoblastic leukemia who were aged 9 to 15 1/2 years and had been
treated with prophylactic central nervous system radiation and combined
chemotherapy. At the time of study, the mean height was -1.5 SD score below
the mean, less than genetic potential, and significantly less than the mean
pretreatment height of -0.25 SD score. Height velocity was subnormal for
age and sexual stage in all patients. Two patients had compensated
hypothyroidism, and four had evidence of gonadal failure. In 11 patients,
the peak GH level after two provocative tests was below 10 micrograms/L,
which was consistent with GH deficiency. In ten of 13 patients tested,
spontaneous GH secretion determined by a 24-hour GH concentration (GHC), GH
pulse amplitude, frequency of GH pulses greater than or equal to 5
micrograms/L, and GH peak during wake and sleep hours was significantly
less than in normal height controls. Although in three pubertal patients
the 24-hour GHC was within normal limits, the GHC during sleep hours, GH
pulse amplitude during 24 hours and sleep hours, and peak GH during wake
hours were significantly less than in normal height controls. In all
pubertal and in two of the prepubertal patients, the somatomedin C (SmC)
level was significantly less than in controls. The 24-hour GHC correlated
well with the GHC during sleep, peak-stimulated GH level, gonadal steroid
level, and the SmC level, but not with height velocity, dose of radiation,
or age at radiation. A significant increase in height velocity and the SmC
level was noted in all patients treated with GH. These results indicate
that GH deficiency occurs after 18 to 24 Gy of cranial radiation and that
the puberty-associated growth spurt may mask the decline in height velocity
owing to GH deficiency. In some patients treated with cranial radiation, a
subtle dysregulation in spontaneous GH secretion may exist despite a normal
GH response to provocative testing.
