Late Effects of Treatment for Childhood Cancer (PDQ®): Treatment - Health Professional Information [NCI] - Late Effects of the Endocrine System
Several investigations have demonstrated the superiority of ultrasound to clinical exam for detecting thyroid nodules/cancers and characterized ultrasonographic features of nodules that are more likely to be malignant.[15,16] However, primary screening for thyroid neoplasia (beyond physical exam with thyroid palpation) remains controversial because of the lack of data indicating a survival benefit and quality-of-life benefit associated with early detection and intervention. In fact, because these lesions tend to be indolent, are rarely life-threatening, and may clinically manifest many years after exposure to radiation, there are significant concerns regarding the costs and harms of overscreening.
(Refer to the Subsequent Neoplasms section of this summary for information about subsequent thyroid cancers.)
Posttransplant thyroid dysfunction
Survivors of pediatric hematopoietic stem cell transplant are at increased risk of thyroid dysfunction, with the risk being much lower (15%-16%) after fractionated total-body irradiation (TBI), as opposed to single-dose TBI (46%-48%). Non-TBI-containing regimens historically were not associated with an increased risk. However, in a report from the Fred Hutchinson Cancer Research Center, the increased risk of thyroid dysfunction was not different between children receiving a TBI or busulfan-based regimen (P = .48). Other high-dose therapies have not been studied. While mildly elevated TSH is common, it is usually accompanied by normal thyroxine concentration.[19,20]
Table 7. Thyroid Late Effects
|Predisposing Therapy||Endocrine/Metabolic Effects||Health Screening|
|mIBG = metaiodobenzylguanidine; TSH = thyroid stimulating hormone.|
|Radiation impacting thyroid gland; thyroidectomy||Primary hypothyroidism||TSH level|
|Radiation impacting thyroid gland||Hyperthyroidism||Free thyroxine (Free T4) level|
|Radiation impacting thyroid gland, including mIBG||Thyroid nodules||Thyroid exam|
Central hypothyroidism is discussed with late effects that affect the pituitary gland.
Survivors of childhood cancer are at risk for a spectrum of neuroendocrine abnormalities, primarily due to the effect of radiation therapy on the hypothalamus. Essentially all of the hypothalamic-pituitary axes are at risk.[21,22,23] The six anterior pituitary hormones and their major hypothalamic regulatory factors are outlined in Table 8.
Table 8. Anterior Pituitary Hormones and Major Hypothalamic Regulatory Factors
|Pituitary Hormone||Hypothalamic Factor||Hypothalamic Regulation of the Pituitary Hormone|
|(-) = inhibitory; (+) = stimulatory.|
|Growth hormone||Growth hormone-releasing hormone||+|
|Luteinizing hormone||Gonadotropin-releasing hormone||+|
|Follicle-stimulating hormone||Gonadotropin-releasing hormone||+|
|Thyroid-stimulating hormone||Thyroid-releasing hormone||+|
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. The prevalence in pooled analysis was found to be approximately 35.6%. 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.