RERF Report No. 9-14§

Paper published in JAMA Internal Medicine“Association of Radiation Dose With Prevalence of Thyroid Nodules Among
Atomic Bomb Survivors Exposed in Childhood (2007-2011)”
Misa Imaizumi, Waka Ohishi, Eiji Nakashima, Nobuko Sera, Kazuo Neriishi, MichikoYamada, Yoshimi Tatsukawa, Ikuno Takahashi, Saeko Fujiwara, Takao Ando, Toshiro
Usa, Atsushi Kawakami, Masazumi Akahoshi, and Ayumi Hida
JAMA Intern Med 2015 (February); 175(2):228-236(doi: 10.1001/jamainternmed.2014.6692)
Study Findings
A thyroid study conducted among A-bomb survivors 62–66 years after exposure toradiation in childhood (at less than 10 years of age) revealed a significant association
between the prevalence* of larger thyroid nodules (those with a diameter of 10 mm or
more, or those with past surgery for a nodule) and A-bomb radiation dose to the thyroid;
however, no association was observed for small nodules of less than 10 mm in diameter.
*The term “prevalence” here refers to the percentage of the population with a diseaseat the time of examination, regardless of whether or not they had been previously
diagnosed.
Explanation
Adult Health Study (AHS) participants were examined to investigate the association
between thyroid nodules and A-bomb radiation in survivors exposed in childhood (atless than 10 years of age). The AHS has examined the health status of A-bomb survivors
in Hiroshima and Nagasaki since 1958 through biennial medical assessments.
[Note]The term thyroid nodule refers to a benign or malignant growth in the thyroidgland. Thyroid ultrasound-based observation classifies such nodules into two major
types: cysts or solid nodules. Nearly all cysts are benign, while solid nodules arefurther classified into malignant tumors (mostly cancers) and benign nodules. Benign
nodules include benign tumors, hyperplasia, and thyroiditis-related nodules. Thyroid
nodules that are not malignant usually do not require treatment; however, in the caseof large nodules with pressure symptoms or when the possibility of malignancy
cannot be ruled out, treatment may be necessary. This study focused on relatively
large thyroid nodules (diameter of 10 mm or more, or post-surgical cases), which arelikely to emerge as a clinical problem. The study also reviewed small nodules lessthan 10 mm in diameter, which are unlikely to be a clinical problem.
1.

Objectives
It is known that the risk of thyroid cancer is higher after radiation exposure inchildhood compared with exposure in adulthood. Determining whether or not the effectsof radiation exposure on the thyroid appear among adults many years after exposure inchildhood is an important public health issue. On the other hand, thyroid
ultrasonography can detect thyroid nodules in 17–67% of the general population who
have had little exposure to radiation. This study aims to elucidate the association
between thyroid nodules and A-bomb radiation among A-bomb survivors more than 60years after exposure in childhood.
2.

Methods
Thyroid examinations, including thyroid ultrasonography, were conducted on 3,087
A-bomb survivors participating in the AHS between 2007 and 2011 who were less than
10 years old at the time of exposure. The study investigated the association of thyroid
dose with the prevalence of larger thyroid nodules (diameter of 10 mm or more, orpost-surgical cases), as well as small thyroid nodules (diameter of less than 10 mm)
among 2,688 survivors for whom A-bomb radiation dose to the thyroid had been
estimated. The mean age of participants was 68.2 years; 1,213 were males and 1,455
females; the median dose was 0.182 Gy (182 mGy); and the dose range was 0–4.040
Gy.
3. Results(1) The prevalence (17.6% of those examined) of larger thyroid nodules (diameter of 10mm or more, or post-surgical cases) was significantly associated with thyroid
radiation dose; the estimated excess odds ratio** per gray (Gy) of thyroid dose was
1.65 (95% Confidence Interval (CI): 0.89, 2.64). We conducted the analyses byclassifying the thyroid nodules into solid nodules and cysts, and then further
classifying the solid nodules as malignant tumors or benign nodules. Respective
analyses detected a significant association between nodule prevalence and thyroid
dose.
**In this study, we considered the odds ratio to be nearly equivalent torelative risk; The odds ratio represents how many times higher the risk is forthe radiation-exposed group than for the control group (i.e., those with aradiation dose of zero Gy). The excess odds ratio is represented by the odds
ratio minus one and shows the portion of relative risk that can be attributed toradiation exposure.
(2) The study revealed that age at exposure significantly affected the association
between the prevalence of larger thyroid nodules (diameter of 10 mm or more, or
post-surgical cases) and radiation, and that the effects of radiation were greaterwith earlier childhood exposure. On the other hand, the radiation risk did not vary
substantially by sex, family history of thyroid disease, presence of antithyroid
antibodies, or intake of seaweed.
[Note]
Generally speaking, thyroid nodules occur with greater frequency in females
and in those with a family history of thyroid disease and are also frequently
observed in chronic thyroiditis patients (those with positive blood tests for
antithyroid antibodies). It is also known that the nodules are affected by intakeof iodine, and seaweed is rich in iodine. Consequently, we examined whether
or not these factors affected the degree of radiation risk for thyroid nodules.
(3) No significant association was observed between small thyroid nodules (diameterof less than 10 mm) and radiation dose to the thyroid.
More than 60 years after exposure to radiation in childhood, instances of larger
thyroid nodules (diameter of 10 mm or more, or post-surgical cases) wereassociated with radiation dose; however, such an association was not observed forsmall thyroid nodules (diameter of less than 10 mm). The term thyroid nodule
refers to a variety of clinical states, including cancers, benign tumors, hyperplasia,and thyroiditis-related changes. The difference in effects of radiation in relation tothe size of nodules may provide clues to the mechanisms through which radiation
exposure affects the clinical state of thyroid nodules.
The Radiation Effects Research Foundation has studied A-bomb survivors and theiroffspring in Hiroshima and Nagasaki for more than 60 years. RERF’s researchachievements are considered the principal scientific basis for radiation risk assessmentby the United Nations Scientific Committee on the Effects of Atomic Radiation(UNSCEAR) and for recommendations regarding radiation protection standards by theInternational Commission on Radiological Protection (ICRP). RERF expresses its
profound gratitude to the A-bomb survivors and survivors’ offspring for theircooperation in our studies.§§

JAMA Internal Medicine is a peer-reviewed international journal published by theAmerican Medical Association. The journal publishes innovative, clinically relevant
research for practitioners in general internal medicine and internal medicine
subspecialties. (Impact Factor in 2013: 13.25)