1633 / 1708
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
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
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
Time After RT
Start (months)
Mean Dose to
Hypothalamus (Gy)
36-Month Data (GH, ng/mL)*
60-Month Data (GH, ng/mL)†
Probability
of 7
Probability
of 3
Predicted
Mean Peak
Probability
of 7
Probability
of 3
Predicted
Mean Peak
12
5
0.15
0.0093
13.55
0.16
0.0107
13.07
10
0.18
0.0120
12.73
0.18
0.0130
12.46
15
0.20
0.0154
11.96
0.20
0.0157
11.89
20
0.23
0.0196
11.23
0.23
0.0189
11.34
25
0.26
0.0247
10.55
0.25
0.0226
10.81
30
0.29
0.0309
9.92
0.27
0.0269
10.31
35
0.33
0.0383
9.32
0.30
0.0318
9.83
40
0.36
0.0472
8.75
0.32
0.0375
9.38
45
0.40
0.0576
8.22
0.35
0.0439
8.94
50
0.44
0.0697
7.73
0.38
0.0513
8.53
55
0.48
0.0837
7.26
0.41
0.0595
8.13
60
0.52
0.0998
6.82
0.44
0.0688
7.76
36
5
0.19
0.0135
12.36
0.18
0.0131
12.44
10
0.28
0.0274
10.25
0.25
0.0227
10.79
15
0.38
0.0518
8.50
0.32
0.0377
9.36
20
0.50
0.0910
7.05
0.41
0.0599
8.12
25
0.61
0.1486
5.85
0.50
0.0912
7.04
30
0.72
0.2267
4.85
0.58
0.1332
6.11
35
0.81
0.3237
4.02
0.67
0.1869
5.30
40
0.88
0.4346
3.33
0.74
0.2524
4.60
45
0.93
0.5508
2.77
0.81
0.3282
3.99
50
0.96
0.6628
2.29
0.86
0.4119
3.46
55
0.98
0.7620
1.90
0.91
0.4998
3.00
60
0.99
0.8426
1.58
0.94
0.5877
2.60
60
5
0.23
0.0193
11.28
0.21
0.0160
11.84
10
0.40
0.0569
8.26
0.33
0.0379
9.34
15
0.59
0.1369
6.04
0.47
0.0800
7.37
20
0.76
0.2720
4.42
0.61
0.1504
5.82
25
0.89
0.4526
3.24
0.75
0.2533
4.59
30
0.95
0.6437
2.37
0.85
0.3844
3.62
35
0.99
0.8039
1.74
0.92
0.5305
2.86
40
1.00
0.9104
1.27
0.96
0.6725
2.25
45
1.00
0.9664
0.93
0.98
0.7931
1.78
50
1.00
0.9898
0.68
0.99
0.8825
1.40
55
1.00
0.9975
0.50
1.00
0.9403
1.11
60
1.00
0.9995
0.37
1.00
0.9731
0.87
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
) }).
Growth Hormone Secretion After Hypothalamic Irradiation
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