Peter D Inskip1, Lene H S Veiga2, Alina V Brenner3, Alice J Sigurdson4, Evgenia Ostroumova5, Eric J Chow6, Marilyn Stovall7, Susan A Smith8, Wendy Leisenring6, Leslie L Robison9, Gregory T Armstrong9, Charles A Sklar10, Jay H Lubin11. 1. Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland; Retired. Electronic address: inskippeter@gmail.com. 2. Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland. 3. Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland; Radiation Effects Research Foundation, Hiroshima, Japan. 4. Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland; Retired. 5. Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland; International Agency for Research on Cancer, Lyon, France. 6. Clinical Research and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington. 7. Retired; Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas. 8. Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas. 9. Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee. 10. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York. 11. Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland.
Abstract
PURPOSE: The association of hyperthyroidism with exposure to ionizing radiation is poorly understood. This study addresses the risk of hyperthyroidism in relation to incidental therapeutic radiation dose to the thyroid and pituitary glands in a large cohort of survivors of childhood cancer. METHODS AND MATERIALS: Using the Childhood Cancer Survivor Study's cohort of 5-year survivors of childhood cancer diagnosed at hospitals in the United States and Canada between 1970 and 1986, the occurrence of hyperthyroidism through 2009 was ascertained among 12,183 survivors who responded to serial questionnaires. Radiation doses to the thyroid and pituitary glands were estimated from radiation therapy records, and chemotherapy exposures were abstracted from medical records. Binary outcome regression was used to estimate prevalence odds ratios (ORs) for hyperthyroidism at 5 years from diagnosis of childhood cancer and Poisson regression to estimate incidence rate ratios (RRs) after the first 5 years. RESULTS: Survivors reported 179 cases of hyperthyroidism, of which 148 were diagnosed 5 or more years after their cancer diagnosis. The cumulative proportion of survivors diagnosed with hyperthyroidism by 30 years after the cancer diagnosis was 2.5% (95% confidence interval [CI], 2.0%-2.9%) among those who received radiation therapy. A linear relation adequately described the thyroid radiation dose response for prevalence of self-reported hyperthyroidism 5 years after cancer diagnosis (excess OR/Gy, 0.24; 95% CI, 0.06-0.95) and incidence rate thereafter (excess RR/Gy, 0.06; 95% CI, 0.03-0.14) over the dose range of 0 to 63 Gy. Neither radiation dose to the pituitary gland nor chemotherapy was associated significantly with hyperthyroidism. Radiation-associated risk remained elevated >25 years after exposure. CONCLUSIONS: Risk of hyperthyroidism after radiation therapy during childhood is positively associated with external radiation dose to the thyroid gland, with radiation-related excess risk persisting for >25 years. Neither radiation dose to the pituitary gland nor chemotherapy exposures were associated with hyperthyroidism among childhood cancer survivors through early adulthood.
PURPOSE: The association of hyperthyroidism with exposure to ionizing radiation is poorly understood. This study addresses the risk of hyperthyroidism in relation to incidental therapeutic radiation dose to the thyroid and pituitary glands in a large cohort of survivors of childhood cancer. METHODS AND MATERIALS: Using the Childhood Cancer Survivor Study's cohort of 5-year survivors of childhood cancer diagnosed at hospitals in the United States and Canada between 1970 and 1986, the occurrence of hyperthyroidism through 2009 was ascertained among 12,183 survivors who responded to serial questionnaires. Radiation doses to the thyroid and pituitary glands were estimated from radiation therapy records, and chemotherapy exposures were abstracted from medical records. Binary outcome regression was used to estimate prevalence odds ratios (ORs) for hyperthyroidism at 5 years from diagnosis of childhood cancer and Poisson regression to estimate incidence rate ratios (RRs) after the first 5 years. RESULTS: Survivors reported 179 cases of hyperthyroidism, of which 148 were diagnosed 5 or more years after their cancer diagnosis. The cumulative proportion of survivors diagnosed with hyperthyroidism by 30 years after the cancer diagnosis was 2.5% (95% confidence interval [CI], 2.0%-2.9%) among those who received radiation therapy. A linear relation adequately described the thyroid radiation dose response for prevalence of self-reported hyperthyroidism 5 years after cancer diagnosis (excess OR/Gy, 0.24; 95% CI, 0.06-0.95) and incidence rate thereafter (excess RR/Gy, 0.06; 95% CI, 0.03-0.14) over the dose range of 0 to 63 Gy. Neither radiation dose to the pituitary gland nor chemotherapy was associated significantly with hyperthyroidism. Radiation-associated risk remained elevated >25 years after exposure. CONCLUSIONS: Risk of hyperthyroidism after radiation therapy during childhood is positively associated with external radiation dose to the thyroid gland, with radiation-related excess risk persisting for >25 years. Neither radiation dose to the pituitary gland nor chemotherapy exposures were associated with hyperthyroidism among childhood cancer survivors through early adulthood.
Authors: Parveen Bhatti; Lene H S Veiga; Cécile M Ronckers; Alice J Sigurdson; Marilyn Stovall; Susan A Smith; Rita Weathers; Wendy Leisenring; Ann C Mertens; Sue Hammond; Debra L Friedman; Joseph P Neglia; Anna T Meadows; Sarah S Donaldson; Charles A Sklar; Leslie L Robison; Peter D Inskip Journal: Radiat Res Date: 2010-10-06 Impact factor: 2.841
Authors: Lene H S Veiga; Erik Holmberg; Harald Anderson; Linda Pottern; Siegal Sadetzki; M Jacob Adams; Ritsu Sakata; Arthur B Schneider; Peter Inskip; Parveen Bhatti; Robert Johansson; Gila Neta; Roy Shore; Florent de Vathaire; Lena Damber; Ruth Kleinerman; Michael M Hawkins; Margaret Tucker; Marie Lundell; Jay H Lubin Journal: Radiat Res Date: 2016-04-29 Impact factor: 2.841
Authors: Peter D Inskip; Lene H S Veiga; Alina V Brenner; Alice J Sigurdson; Evgenia Ostroumova; Eric J Chow; Marilyn Stovall; Susan A Smith; Rita E Weathers; Wendy Leisenring; Leslie L Robison; Gregory T Armstrong; Charles A Sklar; Jay H Lubin Journal: Radiat Res Date: 2018-05-15 Impact factor: 2.841
Authors: M Iitaka; N Momotani; T Hisaoka; J Y Noh; N Ishikawa; J Ishii; S Katayama; K Ito Journal: Clin Endocrinol (Oxf) Date: 1998-04 Impact factor: 3.478
Authors: Lene H S Veiga; Jay H Lubin; Harald Anderson; Florent de Vathaire; Margaret Tucker; Parveen Bhatti; Arthur Schneider; Robert Johansson; Peter Inskip; Ruth Kleinerman; Roy Shore; Linda Pottern; Erik Holmberg; Michael M Hawkins; M Jacob Adams; Siegal Sadetzki; Marie Lundell; Ritsu Sakata; Lena Damber; Gila Neta; Elaine Ron Journal: Radiat Res Date: 2012-08-02 Impact factor: 2.841