paediatrics Brussels 17

Growth Hormone Secretion After Hypothalamic Irradiation

Table 1. Probability of GHD by Mean Dose to the Hypothalamus and Time After Irradiation Using Peak GH Data Through 36 and 60 Months After Conformal RT

36-Month Data (GH, ng/mL)*

60-Month Data (GH, ng/mL)†

Time After RT Start (months)

Mean Dose to Hypothalamus (Gy)

Probability of 7

Probability of 3

Predicted Mean Peak

Probability of 7

Probability of 3

Predicted Mean Peak

12

5

0.15 0.18 0.20 0.23 0.26 0.29 0.33 0.36 0.40 0.44 0.48 0.52 0.19 0.28 0.38 0.50 0.61 0.72 0.81 0.88 0.93 0.96 0.98 0.99 0.23 0.40 0.59 0.76 0.89 0.95 0.99 1.00 1.00 1.00 1.00 1.00

0.0093 0.0120 0.0154 0.0196 0.0247 0.0309 0.0383 0.0472 0.0576 0.0697 0.0837 0.0998 0.0135 0.0274 0.0518 0.0910 0.1486 0.2267 0.3237 0.4346 0.5508 0.6628 0.7620 0.8426 0.0193 0.0569 0.1369 0.2720 0.4526 0.6437 0.8039 0.9104 0.9664 0.9898 0.9975 0.9995

13.55 12.73 11.96 11.23 10.55

0.16 0.18 0.20 0.23 0.25 0.27 0.30 0.32 0.35 0.38 0.41 0.44 0.18 0.25 0.32 0.41 0.50 0.58 0.67 0.74 0.81 0.86 0.91 0.94 0.21 0.33 0.47 0.61 0.75 0.85 0.92 0.96 0.98 0.99 1.00 1.00

0.0107 0.0130 0.0157 0.0189 0.0226 0.0269 0.0318 0.0375 0.0439 0.0513 0.0595 0.0688 0.0131 0.0227 0.0377 0.0599 0.0912 0.1332 0.1869 0.2524 0.3282 0.4119 0.4998 0.5877 0.0160 0.0379 0.0800 0.1504 0.2533 0.3844 0.5305 0.6725 0.7931 0.8825 0.9403 0.9731

13.07 12.46 11.89 11.34 10.81 10.31

10 15 20 25 30 35 40 45 50 55 60 10 15 20 25 30 35 40 45 50 55 60 10 15 20 25 30 35 40 45 50 55 60 5 5

9.92 9.32 8.75 8.22 7.73 7.26 6.82 8.50 7.05 5.85 4.85 4.02 3.33 2.77 2.29 1.90 1.58 8.26 6.04 4.42 3.24 2.37 1.74 1.27 0.93 0.68 0.50 0.37

9.83 9.38 8.94 8.53 8.13 7.76 9.36 8.12 7.04 6.11 5.30 4.60 3.99 3.46 3.00 2.60 9.34 7.37 5.82 4.59 3.62 2.86 2.25 1.78 1.40 1.11 0.87

36

12.36 10.25

12.44 10.79

60

11.28

11.84

Abbreviations: GH, growth hormone; GHD, growth hormone deficiency; RT, radiation therapy. *36-month model: peak GH exp(2.6518 { time 0.001385 (0.00104 mean dose ) }). †60-month model: peak GH exp(2.5947 { time 0.0019 (0.00079 mean dose ) }).

addition to radiation dose to the hypothalamus, CSF shunting is an important risk factor for GHD both before and after irradiation. Endocrine deficiencies cannot always be predicted by tumor lo- cation. This observation highlights the contribution of scattered radi- ation 20 and the need for more accurate estimates of hypothalamic radiation dose. Clinical data describing neuroendocrine effects of irradiation have been derived by using generalized estimates of radia- tion dose under conditions in which the dose to the hypothalamic- pituitary axis was generally homogeneous and discrete. Examples include patients treated with single-dose or fractionated total-body irradiation (8 to 14 Gy), those given cranial irradiation for acute lymphoblastic leukemia (18 Gy and 24 Gy), and those with tumors of the sella or parasellar region in which the hypothalamic-pituitary axis was uniformly included in the volume of prescribed dose ( 50 Gy). Radiation is a significant contributor to neuroendocrine complications commonly observed after treatment for brain tumors and tumors of the

standard in the sequelae and treatment of severe hydrocephalus. Pre-existing GHD was also related to tumor diagnosis and tumor location. These variables are often correlated, considering the sin- gular suprasellar location of craniopharyngioma and the fact that the diencephalon or optic pathway is the most commonly irradiated site in childhood low-grade glioma. Because these tumors are inti- mately associated with the hypothalamus, these patients have a high likelihood of postradiation GHD if it is not already present before irradiation. All factors considered, our data suggest a need for early evaluation and intervention in these patients. Children with ependymoma often present with obstructive hy- drocephalus originating in the posterior fossa. The direct effect of hydrocephalus on the hypothalamus fromincreased intracranial pres- sure and expansion of the ventricular system should not be underes- timated. Although tumor resection may relieve the obstruction, permanent CSF shunting is required for the most severe cases. In

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