Risk to the Thyroid from Ionizing Radiation

ReportNo_159 BY aSd......Page 1
Front Matter......Page 2
Preface.pdf......Page 4
Table of Contents......Page 7
Purpose and Rationale......Page 16
Synopsis of This Report......Page 18
Conclusions......Page 27
Recommendations......Page 28
1. Introduction......Page 32
1.1.1 Radioiodine Production and Use in the Study of Thyroid Physiology......Page 33
1.1.2 Use of Radioiodine in Medical Treatment......Page 34
1.1.3 Radiation Effects on the Thyroid Observed in Patients......Page 35
1.1.4 Radioiodine in the Environment......Page 38
1.2.2 Radiation Dosimetry and Dose Reconstruction......Page 42
1.2.5 Screening for Thyroid Disease Following Radiation Exposure......Page 44
1.2.7 Appendices......Page 45
2.1.1 Anatomy......Page 46
2.1.2 Physiology......Page 49
2.1.2.1 Iodine Metabolism......Page 50
2.1.2.2 Thyroid Hormone Metabolism......Page 53
2.1.2.3 Regulatory Effects of Stable Iodine......Page 55
2.2 Diseases of the Thyroid and Parathyroid Glands......Page 57
2.2.1 Benign Thyroid Nodules......Page 58
2.2.2 Thyroid Cancer......Page 59
2.2.2.1 Thyroid Cancers in Adults......Page 60
2.2.2.2 Thyroid Cancers in Children......Page 63
2.2.3.1 Hyperthyroidism......Page 64
2.2.3.2 Hypothyroidism......Page 65
2.3 Medical Uses of Radiation......Page 66
2.3.2 Diagnostic Use of Radioactive Tracers in the Thyroid......Page 67
2.3.3 Radioactive Iodine Therapy......Page 68
2.3.4 Thyroid Dose from Radioactive Iodine......Page 70
2.4 Thyroid Genomics......Page 71
2.4.1 DNA Damage and Cellular Response......Page 72
2.4.2.2 Technical Requirements......Page 75
2.4.2.3 Oncogenesis, Mitotic Rate, and Growth Potential......Page 76
3.1 Specification of Dose in Principle and in Practice......Page 78
3.1.2 Specification of Dose: Practical......Page 79
3.1.2.1 Physical Dosimetry......Page 80
3.1.2.2 Biological Dosimetry......Page 81
3.2.1 Medical External Radiation Exposure......Page 82
3.2.2 External Radiation Exposure Associated with the Atomic Bombings of Hiroshima and Nagasaki......Page 83
3.3.1 Radioisotopes of Iodine......Page 87
3.3.2 Age-Dependent Thyroid Absorbed Doses from Radioisotopes of Iodine......Page 94
3.3.3 Environmental Dispersion of Radioiodine......Page 102
3.3.4 Potassium Iodide Blockade of Radioiodine Uptake in the Thyroid......Page 107
3.3.5 Limitations of the Radiobiological Significance of Iodine-129......Page 110
3.3.6 Spatial and Temporal Inhomogeneities in Intrathyroidal Radioiodine Distribution and Absorbed Dose......Page 113
3.3.7 Dose Assessment of Major Environmental Releases of Radioiodines......Page 117
3.3.7.1 Nevada Test Site Cohort Exposed to ^131I-Contaminated Fallout......Page 119
3.3.7.2 Marshall Islanders......Page 122
3.3.7.3 Hanford Site......Page 126
3.3.7.4 Chernobyl Nuclear Reactor Accident......Page 129
3.4 Radiation Dosimetry in Specific Epidemiological Studies of Radiogenic Thyroid Disease......Page 134
4. Radiation Effects......Page 158
4.1.1 Experiments with Rodents......Page 159
4.1.2 Experiments in Larger Animals......Page 161
4.1.3 Experiments to Determine Relative Biological Effectiveness......Page 162
4.2 Types of Epidemiologic Studies......Page 164
4.2.1 Cohort Studies......Page 168
4.2.2 Case-Control Studies......Page 169
4.2.3 Clinical Screening Studies......Page 170
4.2.4 Ecological (Aggregate) Studies......Page 171
4.3 Methodological Issues Regarding Studies of Radiation and Thyroid Tumors......Page 172
4.3.1 Sources of Uncertainty in Epidemiological Studies......Page 173
4.3.2 Incidence versus Mortality Data......Page 174
4.3.3 Micro-Carcinomas and Screening for Thyroid Disease......Page 176
4.4 Human Thyroid Cancer Following External Irradiation......Page 178
4.4.1 Atomic-Bomb Survivors Study......Page 179
4.4.2 Rochester Thymus Study......Page 189
4.4.3 Israeli Tinea Capitis Study......Page 190
4.4.4 Chicago Head and Neck Irradiation Study......Page 191
4.4.5 Boston Lymphoid Hyperplasia Study......Page 193
4.4.6 Childhood Cancer Survivor Study......Page 194
4.4.7 Swedish Skin Hemangioma Studies (Gothenburg and Stockholm)......Page 196
4.5 Human Thyroid Cancer Following Internal Irradiation......Page 197
4.5.1.1 Swedish Diagnostic ^131I Study......Page 198
4.5.1.2 FDA Childhood Diagnostic ^131I Study......Page 204
4.5.1.4 Summary of Thyroid Cancers Following Diagnostic Internal Irradiation with ^131I......Page 205
4.5.2.1 Swedish Hyperthyroid Study......Page 206
4.5.2.2 U.S. Cooperative Thyrotoxicosis Therapy Follow-up Study......Page 207
4.5.2.3 British Hyperthyroid Study......Page 208
4.5.3 Environmental Iodine-131 Studies......Page 209
4.5.3.1 Nevada Test Site......Page 210
4.5.3.2 Fallout from Nuclear Weapons Testing......Page 211
4.5.3.3 Marshall Islanders......Page 212
4.5.3.4 Semipalatinsk Nuclear Test Site......Page 215
4.5.3.5 Hanford Site......Page 216
4.5.3.6 Chernobyl Environmental Exposure......Page 218
4.5.3.8 Chernobyl Occupational Exposure......Page 232
4.6.1.1 Robert Packer Hospital Head and Neck Study......Page 235
4.6.1.2 French Hemangiomas Study......Page 236
4.6.1.4 Chicago Head and Neck Irradiation Study......Page 243
4.6.2 Stockholm Medical Diagnostic Iodine-131 Study......Page 244
4.6.3.2 Hiroshima Autopsy Study......Page 245
4.6.3.4 Thyroid Disease Prevalence......Page 246
4.6.4.1 Chernobyl Cleanup Workers Study......Page 247
4.6.4.2 Chinese High Background Study......Page 248
4.6.4.3 India High Background Study......Page 249
4.7.1 Thyroid Function Following External Beam Radiation Therapy......Page 250
4.7.2 Thyroid Function Following Radioiodine Therapy......Page 252
4.7.3.1 Marshall Islands Fallout......Page 253
4.7.3.2 Nevada Test Site......Page 254
4.7.3.4 Evidence from Atomic-Bomb Survivors in Nagasaki and Hiroshima......Page 256
4.7.3.5 Chernobyl Nuclear Reactor Accident......Page 259
4.7.4 Summary of Major Points of the Medical Literature Review......Page 262
4.8.1.1 Quantitative Abnormalities in Nuclear DNA......Page 263
4.8.1.2 Chromosome Banding Studies......Page 264
4.8.1.3 Fluorescent Chromosome Specific Analysis......Page 265
4.8.2 Specific Oncogene Activation......Page 266
4.8.2.1 RET Proto-Oncogene Activation......Page 267
4.8.2.3 Bystander Effects of Ionizing Radiation......Page 268
4.9 Parathyroid Function......Page 269
4.9.1 Swedish Tuberculous Adenitis Study......Page 270
4.9.4 Chicago Head and Neck Irradiation Study......Page 271
4.10 Conclusions......Page 272
5. Radiation Risk for Thyroid Neoplasms......Page 274
5.1 Dose-Response Relationships......Page 275
5.1.1 Excess Absolute Risk Model......Page 276
5.1.2 Excess Relative Risk Model......Page 279
5.2 Past Risk Estimates and Models......Page 282
5.3.1 Analyses of External Radiation Data on Thyroid Cancer......Page 285
5.3.1.1 Shape of the Dose-Response Curve......Page 288
5.3.1.2 Effect of Dose Uncertainty on the Risk Estimates......Page 290
5.3.2.1 Variation in Risk by Age at Exposure......Page 293
5.3.2.2 Variation in Risk by Time Since Exposure or Attained Age......Page 294
5.3.2.3 Variation in Thyroid Cancer Risk by Sex......Page 297
5.3.2.4 Variation in Thyroid Cancer Risk by Ethnicity......Page 298
5.3.2.6 Hereditary Factors and Radiation-Induced Thyroid Cancer......Page 300
5.3.3.1 Estimated EAR (10^4 PY Gy)^-1 for External, Low-LET Radiation......Page 301
5.3.3.2 Estimated ERR Gy^-1 for External, Low-LET Radiation......Page 302
5.3.3.3 Temporal Aspects of Risk Models for Thyroid Cancer......Page 303
5.3.3.4 Comparison of Risk Models for Thyroid Cancer......Page 305
5.3.4 Estimates of Lifetime Risks of Thyroid Cancer from External Exposure: Results and Comparison of Models 1 through 6......Page 309
5.3.5 Estimation of Lifetime Thyroid Cancer Mortality Risk......Page 317
5.3.6 Internal-Exposure Risk Estimates for Thyroid Cancer: Relative Biological Effectiveness......Page 321
5.4.1 Acute External Exposure in Childhood or Adolescence......Page 328
5.4.3 Discussion and Conclusions Regarding Radiation Risk of Thyroid Nodules......Page 329
5.5 Summary of Radiation Risk of Thyroid Disease......Page 330
6.1 Background......Page 333
6.1.1 National Cancer Institute Workshop......Page 334
6.1.3 National Academy of Sciences Report......Page 335
6.2 Conclusions......Page 337
7.1 Conclusions......Page 338
7.2 Research Recommendations......Page 345
A.2 Exposure......Page 347
Index......Page 0
A.3 Absorbed Dose and Specific Energy......Page 351
A.5 Linear Energy Transfer and Lineal Energy......Page 353
A.6 Relative Biological Effectiveness......Page 354
A.7 Quality Factor, Radiation Weighting Factor, Dose Equivalent, and Equivalent Dose......Page 355
A.8 Dose-Rate Effect and Dose and Dose-Rate Effectiveness Factor......Page 356
B.1.1 External Beam Radiation Therapy......Page 358
B.1.2 Brachytherapy......Page 360
B.2 Specification of Dose and Dose Distribution......Page 362
B.3.1 External Beam Radiation Therapy......Page 363
B.3.2 Brachytherapy......Page 367
Appendix C: Technical Aspects of Radiation Dosimetry for the Atomic-Bomb Survivors: The Dosimetry System 1986 and the Dosimetry System 2002......Page 371
Appendix C: Technical Aspects of Radiation Dosimetry for the Atomic-Bomb Survivors: The Dosimetry System 1986 and the Dosimetry System 2002......Page 377
D.1 Radioiodide Pharmacokinetics......Page 383
D.2 Calculation of Internal Dose......Page 384
D.3 Dietary Iodine Levels and Potassium Iodide Blockade......Page 388
E.1.1 University of California Berkeley......Page 391
E.1.2 Post-Graduate Medical School of London......Page 395
E.2 Experiments in Larger Animals......Page 397
E.3 Experiments to Determine Relative Biological Effectiveness......Page 399
F.1.1 Childhood Treatment Studies Published prior to 1965......Page 403
F.1.2 University of Rochester Thymic Enlargement Study......Page 406
F.1.3 Cincinnati Benign Childhood Disease Study......Page 408
F.1.4 University of Chicago Thyroid Unit Study......Page 409
F.1.5 New York Tinea Capitis Study......Page 410
F.2.1 New York Tuberculous Adenitis Study......Page 411
F.2.2 Leiden, Netherlands Study of Irradiation for Benign Head/Neck Conditions......Page 412
F.2.3 Thyroid Cancer and Prior Radiation Therapy......Page 413
F.2.6 Cervical Cancer......Page 414
F.2.7 Radium-226 or X-ray Therapy for Metropathia......Page 415
F.2.9 Stockholm, Sweden Study of Irradiation for Benign Breast Disease......Page 416
F.2.10 French Study of Skin Angioma Patients......Page 417
F.3 Occupational Exposure......Page 418
F.3.2 Chinese Medical X-ray Workers......Page 419
F.4.1 Multiple Fluoroscopic Exams for Tuberculosis Pneumothorax......Page 420
F.4.2 Case-Control Studies......Page 421
G.1 BEIR I......Page 423
G.2 BEIR III......Page 424
G.3 NCRP Report No. 80......Page 426
G.4 BEIR V......Page 429
G.5 UNSCEAR Reports......Page 430
G.6 BEIR VII......Page 431
Appendix H: Supplemental Information on Model Development......Page 432
H.1 Excess Relative and Absolute Risk Estimates for Pooled Analysis of Thyroid Cancer Following Exposure to External Radiation......Page 433
H.2 Supplemental Risk Estimates for Pooled Analysis of Thyroid Cancer Following Exposure to External Radiation......Page 448
Glossary......Page 452
Abbreviations and Acronyms......Page 463
References......Page 465
The NCRP......Page 533
NCRP Publications......Page 542
A......Page 553
B......Page 555
C......Page 559
D......Page 561
E......Page 562
G......Page 564
H......Page 565
I......Page 567
L......Page 570
M......Page 571
N......Page 572
P......Page 573
R......Page 575
S......Page 582
T......Page 583
U......Page 594
W......Page 595