ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Int J Radiat Oncol Biol Phys. 2019 Jun 1;104(2):415–424. inskippeter@gmail.com

Childhood cancer survivors (CCSs) are at increased risk to develop thyroid disease, in particular hypothyroidism, nodular disease and thyroid cancer. Hyperthyroidism is less common but may occur after ionizing radiation exposure, even if the causative mechanisms are not completely clarified.

This study analysed the Childhood Cancer Survivor Study’s cohort of 5-year survivors of childhood cancer diagnosed at hospitals in the US and Canada between 1970 and 1986. The occurrence of hyperthyroidism was ascertained among 12 183 survivors who responded to serial questionnaires. Radiation doses to the thyroid and pituitary gland and chemotherapy exposures were estimated from medical records; 179 self-reported cases of hyperthyroidism were identified, 148/179 were diagnosed 5 or more years after cancer diagnosis.

A significantly higher adjusted incidence rate was associated with female sex, recent calendar year of follow-up, and specific types of cancer (Hodgkin lymphoma, followed by central nervous system neoplasms and leukaemia). However, the most important result of this study is the direct correlation between thyroid radiation dose and prevalence of self-reported hyperthyroidism 5 years after cancer diagnosis. Neither radiation dose to the pituitary gland nor chemotherapy was associated with hyperthyroidism. Even if the relatively small number of patients with hyperthyroidism did not allow the identification of a threshold dose, a linear relation described the thyroid radiation dose-response for hyperthyroidism prevalence 5 years after cancer, with an estimated relative risk of 1.06 per +1 Gy. The next step could be the identification of a cut-off dose, in order to discriminate at risk patients needing a careful and prolonged follow-up. Radiation-induced thyroid damage may cause the expression of both stimulatory and blocking antibodies directed against TSH receptor. It is unclear whether radiation-related hyperthyroidism and radiation-related primary hypothyroidism result from distinct (even if sometimes overlapping) autoimmune pathways. Radiation-related primary hypothyroidism can also result from a direct radiation-induced damage to thyroid cells that does not involve an autoimmune process.

References:

1. Inskip PD, Veiga LHS, Brenner AV, et al. Hypothyroidism after radiation therapy for childhood cancer: A report from the Childhood Cancer Survivor Study. Radiat Res 2018;190:117–32.

2. Chow EJ, Friedman DL, Stovall M, et al. Risk of thyroid dysfunction and subsequent thyroid cancer among survivors of acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 2009;53:432–7.

3. Sklar C, Whitton J, Mertens A, et al. Abnormalities of the thyroid in survivors of Hodgkin’s disease: Data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 2000;85:3227–32.