Adult height after cranial irradiation with 24 Gy: factors and markers of height loss

Abstract

The decrease in adult height of children who have been given cranial irradiation (24 Gy) for acute lymphoblastic leukaemia is attributed to chemotherapy, growth hormone (GH) deficiency and early puberty. This study evaluates the factors involved in the height loss between irradiation and adult height and its markers in 43 patients irradiated at 5.8 +/- 0.4 (SEM) years. The mean height loss was 0.9 +/- 0.2 SD in the children with a normal GH peak (n = 11), 1.7 +/- 0.2 SD in those with a low GH peak and untreated (n = 15) and 0.6 +/- 0.2 SD in those treated with GH (n = 17). The adult height was significantly lower than target height in all three groups. The height loss correlated negatively with the GH peak (p < 0.02) and with the age at onset of puberty (p < 0.05) in the first two groups with spontaneous growth, but not with the chemotherapy regimen or its duration, or the plasma insulin-like growth factor I (IGFI) and its GH-dependent binding protein (BP-3). Early puberty (onset at 8-10 years) occurred in 6 girls from the first two groups. At the first evaluation, 5.6 +/- 0.4 years after irradiation, the GH peak values after arginine-insulin stimulation correlated with the age at irradiation (p < 0.03), taking into account the time since irradiation. The plasma IGFI and BP-3 values were correlated with each other, but not with the GH peak. In conclusion, this study demonstrates the impact of GH deficiency and GH replacement therapy on adult height in children given cranial irradiation for leukaemia. They therefore should be evaluated for their GH secretion 1-2 years after the end of chemotherapy. GH therapy is indicated for those with low GH peak and decreased growth rate or no increase in growth rate despite puberty.

Growth and endocrinological disorders up to 21 years after treatment for acute lymphoblastic leukemia in childhood

“…HSDS in the GH-sufficient group was significantly higher compared to HSDS in the GHdeficient group. Similar observations were made by Adan et al [31] in a group of ALL patients treated with C + I. In that study, the GH provocative tests were not cross-sectional, but were performed from 4 years from diagnosis until final height was obtained.…”

Decreased Adult Height in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study

“…While cranial radiotherapy can affect growth hormone secretion, especially at doses ≥24 Gy (16,21,22), the evidence for growth hormone deficiency following 18 Gy doses has been inconsistent (9,23). The duration of the pubertal growth spurt and peak growth velocity may also be decreased following cranial radiotherapy as a result of growth hormone deficiency (8).…”

Growth and puberty after treatment for acute lymphoblastic leukemia

“…The consequences are especially severe in children, since developing tissue is highly susceptible to damage. The drugs can cause precocious toxic effects, but the late effects are mainly due to RT [9][10][11] . Children who were very young at the time of irradiation tend to develop sequelae such as growth impairment and early puberty 12,13 .…”