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Late Effects of Treatment for Childhood Cancer (PDQ®): Treatment - Health Professional Information [NCI] - Late Effects of the Endocrine System

Table 8. Anterior Pituitary Hormones and Major Hypothalamic Regulatory Factors

Pituitary HormoneHypothalamic FactorHypothalamic Regulation of the Pituitary Hormone
(–) = inhibitory; (+) = stimulatory.
Growth hormoneGrowth hormone-releasing hormone+
Somatostatin
ProlactinDopamine
Luteinizing hormoneGonadotropin-releasing hormone+
Follicle-stimulating hormoneGonadotropin-releasing hormone+
Thyroid-stimulating hormoneThyroid-releasing hormone+
Somatostatin
AdrenocorticotropinCorticotropin-releasing hormone+
Vasopressin+

Growth hormone deficiency

Growth hormone deficiency (GHD) is the first and most common side effect of cranial irradiation in brain tumor survivors. The risk increases with radiation dose and time after treatment. GHD is the earliest hormone deficiency and is sensitive to low doses. Other hormone deficiencies require higher doses and their time to onset is much longer than for GHD.[24] The prevalence in pooled analysis was found to be approximately 35.6%.[25] The potential for neuroendocrine damage is likely to decrease because of the use of more focused radiation therapy and a decrease in dose for some malignancies such as medulloblastoma.

Approximately 60% to 80% of irradiated pediatric brain tumor patients who have received doses greater than 30 Gy will have impaired serum growth hormone (GH) response to provocative stimulation, usually within 5 years of treatment. The dose-response relationship has a threshold of 18 Gy to 20 Gy; the higher the radiation dose, the earlier that GHD will occur after treatment. A study of conformal radiation therapy in children with central nervous system (CNS) tumors indicates that GH insufficiency can usually be demonstrated within 12 months of radiation therapy, depending on hypothalamic dose-volume effects.[26] In a recent report from the St. Jude Children's Research Hospital on data from 118 patients with localized brain tumors that were treated with radiation therapy, peak GH was modeled as an exponential function of time after conformal radiation therapy (CRT) and mean radiation dose to the hypothalamus. The average patient was predicted to develop GHD with the following combinations of time after CRT and mean dose to the hypothalamus: 12 months and more than 60 Gy; 36 months and 25 Gy to 30 Gy; and 60 months and 15 Gy to 20 Gy. A cumulative dose of 16.1 Gy to the hypothalamus would be considered the mean radiation dose required to achieve a 50% risk of GHD at 5 years (TD50/5).[27]

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