Thyroid Abnormalities in Survivors of Childhood Cancer

Abstract

Ob­jec­ti­ve: To investigate the late side effects of childhood cancer therapy on the thyroid gland and to determine the risk factors for development of thyroid disorder among childhood cancer survivors.Methods: One hundred and twenty relapse-free survivors of childhood cancer (aged 6-30 years) were included in this study. The diagnoses of patients were lymphoma, leukemia, brain tumor, rhabdomyosarcoma and nasopharyngeal carcinoma (NPC). The patients were divided into two groups depending on the treatment: group 1-chemotherapy (ChT) only (n=52) and group 2-combination therapy of ChT + radiotherapy (RT) (head/neck/thorax) (n=68). Thyroid function tests, urinary iodine levels, and thyroid gland ultrasound examinations were evaluated in both groups.Results: Incidence of thyroid disease was 66% (n=79) in the survivors. The thyroid abnormalities were: hypothyroidism (HT) (n=32, 27%), thyroid nodules (n=27, 22%), thyroid parenchymal heterogeneity (n=40, 33%), autoimmune thyroiditis (n=36, 30%), and thyroid malignancy (n=3, 2%). While the incidence of HT and thyroid nodules in group 2 was significantly higher than in group 1, the incidence of thyroid parenchymal heterogeneity and autoimmune thyroiditis was similar in the two patient groups. HT and thyroid malignancy were seen only in group 2. In multivariate logistic regression analysis, a history of Hodgkin lymphoma (HL), brain tumor and NPC, as well as cervical irradiation and 5000-5999 cGy doses of radiation were found to constitute risk factors for HT. History of HL and 4000-5999 cGy doses of radiation were risk factors for thyroid nodules. Head/neck irradiation and treatment with platinum derivatives were risk factors for autoimmune thyroiditis. In univariate analysis, a history of NPC, cervical + nasopharyngeal irradiation, and treatment with platinum derivatives were risk factors for thyroid parenchymal heterogeneity.Conclusion: Our results indicate that there is especially an increased risk of HT and thyroid nodules in patients treated with combination therapy of ChT with head/neck/thorax RT. Although chemotherapeutic agents per se do not seem to cause HT, longer follow-up is needed to assess whether or not there is an increased risk for autoimmune thyroiditis and thyroid parenchymal heterogeneity after antineoplastic therapy.

Thyroid Sequelae of Pediatric Cancer Therapy

“…Another recent study also reported that treatment with high-dose chemotherapy was significantly predictive for hypothyroidism [39]. However, additional studies have not found that chemotherapy is a risk factor for hypothyroidism [8, 40]. In terms of additive risk, 2 studies in survivors of a broad spectrum of childhood cancers did not identify a clear contribution of chemotherapy to radiation damage of the HPT axis [37, 41].…”

“…In a prospective study of children with embryonal brain tumors treated with craniospinal irradiation and high-dose chemotherapy, 51% of patients were diagnosed with primary hypothyroidism, and the cumulative incidence was 65% at 4 years [47]. However, prevalence rates of primary hypothyroidism after irradiation for CNS tumors vary highly in the literature and range from 33 to 73% [8, 39, 42, 43, 45, 46, 48]. Primary hypothyroidism also occurs after whole body irradiation given in preparation for bone marrow transplant [49].…”

“…It is the most common thyroid sequela of radiation therapy and can range from asymptomatic compensated hypothyroidism to overt clinical hypothyroidism [4, 8, 18, 20, 21, 42, 44-46]. Compensated hypothyroidism is more common [8, 20, 21, 42, 45], may be transient [20, 21], and is associated with lower doses of radiation to the thyroid, such as would be received with craniospinal irradiation given for medulloblastoma. Children treated for Hodgkin disease have some of the highest rates of hypothyroidism with a relative risk of 17.1 compared with sibling controls; in patients treated with 45 Gy or more, the actuarial risk of hypothyroidism is 50% at 20 years from diagnosis [26].…”

“…Thyroid dysfunction can manifest as primary hyperthyroidism, primary hypothyroidism (either compensated or overt), central hypothyroidism, or a combination of the latter two [22, 23]. Ionizing radiation also increases the risk of both benign and malignant thyroid neoplasms [3, 8, 9, 13, 14, 16, 17, 21, 24-33]. In general, the risk of developing radiation-induced thyroid disease depends on numerous factors, including the age of the child at the time of treatment, the radiation dose delivered to the HPT axis, and the time elapsed since irradiation (Fig.…”

“…The risk for and degree of thyroid dysfunction depends on several factors, primarily the dose of radiation to the thyroid (the higher the dose, the higher the risk; risk greatest with thyroid doses ≥25 Gy) as well as the age of the patient at the time of treatment (the younger the age, the higher the risk; risk greatest <age 5 years) [8, 18, 19, 21, 22, 37, 39, 46, 50, 51]. As would be expected, a reduction of thyroid gland volume occurs after irradiation and is correlated with the risk for the development of hypothyroidism [52, 53].…”