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INDICATIONS FOR USING TO PROTECT THE FROM LOW LEVEL INTERNAL IRRADIATION* JACOB ROBBINS, M.D. Clinical Branch National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland

S INCE Three Mile Island, the possibility that detrimental effects from radioactive fallout might be avoided by appropriate management of an exposed population has been the subject of extensive discussion and debate. Much of this debate has centered on the wisdom of providing potassium iodide to prevent thyroid tumors that might develop after exposure to radioactive iodine. Proponents of the two extreme viewpoints have been heard. Dr. Shleien, reflecting the deliberations at the Food and Drug Administration and the belief that even low doses of radioiodine may be detrimental, proposes that iodide administration should be activated at a low exposure level. Dr. Yalow, supporting the view that the thyroid tumor risk is not life-threatening whereas the dangers of widespread iodide administration are potentially serious, argues against providing iodide to the community at large. I shall attempt to achieve a balance in these two legitimate points of view, and make some proposals that seem to me warranted by our present knowledge of the problem. First, I would make some general observations concerning the type of risks we are considering, based on the analysis by Starr and Whipple.1 I believe we can agree that the probability of fatality from radiation-induced thyroid tumors is extremely low, so that the value of risk avoidance to the individual is not greater than its value to society (Figure 1, Ref. 1). On the other hand, because exposure to accidental radiation does not benefit the individual, even this low risk, if in fact it exists, is unacceptable (Figure 4, Ref. 1) provided that it can be safely and effectively avoided. There- fore, we must consider the cost to society of providing the means for

*Presented in a panel, Protective Value of Potassium Iodide, as part of the Symposium on the Health Aspects of Nuclear Power Plant Incidents held by the Committee on Public Health of the New York Academy of Medicine April 7 and 8, 1983. Address for reprint requests: Dr. Jacob Robbins, Building 10, Room 8N315, National Institutes of Health, Bethesda, Maryland 20205

Bull. N.Y. Acad. Med. IMPLICATIONS FOR POTASSIUM IODIDE 1029

TABLE I. THYROID RISK AFTER X-RAY EXPOSURE IN CHILDREN*

Mean thyroid dose (rads)t 9 17 119 257 449 715 Persons 10,842 1,485 235 427 206 53 Cancers 23 1 1 6 9 5 Adenomas 9 7 8 1 1 15 3 Relative risk or (observedlexpected) t Cancer 4.6 (3) (15) (50) (117) (217) Adenoma > 9 4.6 24 23 36 39 Excess tumors /106 PY-radt t Cancer 8.3 1.6 1.6 2.6 3.8 5.0 Adenoma 12.7 13.5 4.5 6.2 2.8

*Follow-up period - 20 yrs. t9 rad from Ron and Modan, 1980. > 9 rad from Shore, Woodard, Pasternack and Hempelmann, 1980.: tRelative risk, (Excess + Expected)/Expected, was calculated using the number expected that was derived from control study groups. Observed/Expected (numbers in parentheses) used incidence data from the Connecticut Tumor Registry for the number of expected cancers since none were observed in the control study group. ,ttPY-rad = patient years x rads. avoidance and the cost to the individual if the avoidance mechanism itself carries a risk. The former consideration requires a political decision whereas the latter requires a medical decision. My remarks, as were those of my colleagues on this panel, are directed mainly at the medical question: Is it reasonable to expect that individuals will be put at risk? And can this risk be safely counteracted? Our ability to answer the medical question will simplify the task of those responsible for the political decision. The first question to settle is whether radioiodine is a hazard, particular- ly at a low level of exposure. Fortunately, we have reliable data indicating that exposure of a child's thyroid gland to as little as 9 rad from x-ray irra- diation significantly increases the risk of (Table I). Al- though this risk, expressed as cancers/10 PY-rads,* appears to be highest at the lower exposure levels, the fact that the data come either from different sources2)3 or from too few cases: suggests that we should use the average risk, which depends mainly on the more reliable higher-dose data, as a first approximation (Table II). Two factors suggest that these values could be underestimates: The numbers of cancers were obtained from

*Patient years x rads

Vol. 59, No. 10, December 1983 1030 J. ROBBINS

TABLE II. THYROID RISK AFTER X-RAY EXPOSURE IN CHILDREN

Both sexes Females Males Excess tumors/106 PY-rad (Shore et al., 1980)3 Cancers 3.8 5.2 1.8 Adenomas 4.5 6.8 2.6 Relative risk or (observedlexpected)* Cancers (Shore et al., 1980)3 (29) (60) (Ron and Modan, 1980)2 16 4.5

*Cf Table I

TABLE III. THYROID TUMOR LATENCY IN YEARS (SHORE ET AL., 1980)3

Control < 400 rad > 400 rad Cancers 15.8* 27.6 (11. 1, 21.8)t (19.8, 34.4) Adenomas 27.3* 31.9 25.7 (22.7, -----)t (29.4, 36.6) (23.0, 30.9)

*Median t90% confidence limits of the estimate hospital surgical records2 or from follow-up, mainly by correspondence,3 and are probably incomplete. The follow-up period averaged about 20 years, and available data show no decrease in appearance of new cases as the exposed cohort ages. Thus, only part of the induced cancers have been detected and the rate of thyroid cancers coming to clinical attention could increase with time. In fact, the latency in the cancer occurrence often exceeds 20 years (Table III). Tables I and II also show that benign thyroid tumors are induced by low-level external irradiation, and, although the numbers of benign tumors exceed the malignant tumors, the relative risk of inducing cancer is greater, at least at the higher dose levels. This reflects the higher likeli- hood that a thyroid nodule induced by irradiation will be a cancer (about 30 to 40%) than in the unexposed population. It is also seen (Table II) that more induced tumors of both kinds were found in women than in men, although the relative risk of developing thyroid cancer was greater in men in the experience of Shore et al. (but not in that of Ron and Modan in Israel). We must emphasize that all these data were obtained when exposure to

Bull. N.Y. Acad. Med. IMPLICATIONS FOR POTASSIUM IODIDE 1031

TABLE IV. THYROID RISK AFTER RADIOIODINE OR X-RAY EXPOSURE IN ANIMALS

Relative risk 132I 131J X-Ray Mice* (Walinder and Sjdden, 1971)9 4 1 4 (Walinder et al., 1972)" Rats* (Book et al., 1980)" 9 1 Rats (Lee et al., 1982)'7 80 rad: cancer 1 0.7 adenoma 1 0.6 400 rad: cancer 1 1.1 adenoma 1 2.0

*Based on goitrogenesis assay rather than tumor induction. irradiation occurred during early childhood, and that there is little evi- dence that adults are at risk from similar exposures.4 In fact, a recent careful study by Royce et al.,' although purporting to contradict earlier evidence on cancer risk, actually provides evidence that the risk of developing a thyroid tumor may be negligible when the average age at exposure is 18 to 20 years. This report, however, is flawed by the low fraction of the exposed cohort that was examined and the fact that many of the women had received thyroid medication. A key question that needs to be answered is whether internal irradiation of the thyroid from radioiodine is equivalent to external irradiation. That thyroid tumors can be induced by radioiodine is evident not only from animal studies' but also from the experience in the Marshall Islands where 18 of the 29 children on Rongelap exposed to fallout before the age of 10 years developed thryoid nodules.7 The 175 rads of simultaneous external radiation would not have produced this many tumors. The estimate of 275 to 1,150 rads from internal exposure, however, is uncertain and may actually be low,8 and much of this irradiation was derived from short-lived radioiodines which appear to be more effective than 131I in producing thyroid damage (Table IV). Except for one case of leukemia which may have resulted from irradiation, thyroid tumor induction, including cancer, was the major late effect of the exposure in this population. Adults as well as children were affected. There are no other data from which we can derive an accurate risk estimate for radioiodine exposure. Evaluation of the effects of radioiodine fallout in Utah and Nevada,12"13 where no increase in thyroid tumors was

Vol. 59, No. 10, December 1983 1032103 J.J.RBBNROBBINS

TABLE V. THYROID RISK AFTER DIAGNOSTIC 1311 IN SWEDEN (HOLM ET AL., 1980)15.16

< 20 yr > 20 yr Persons 486 9647 Dose (rad) 159 58 Mean follow-up (yrs) 18 18 Cancers: Observed 0 9 Expected < 1 8.3 Calculated* 5.6 48

*Based on an excess of 4/106 PY-rad (x ray) + expected, as given in Table VII. For the entire group based on UNSCEAR risk figures and corrected for thyroid size, Holm et al.16 calculated 47-124 tumor. observed after exposure estimated at 10 to 600 rads, is also flawed by uncertainty in the dose.14 An important recent follow-up of individuals receiving diagnostic 131I in Sweden also failed to reveal an increased incidence of thyroid cancer after a mean exposure of 159 rad in "chil- dren" and 58 rads in adults. i,16a However, the use of a cancer registry to detect the cases would give a low estimate of their number, especially after a mean follow-up of only 18 years, and would not, of course, give the incidence of benign nodules. It is also likely that few of the patients in the < 20 year age group were very young when they were exposed although the estimated average thyroid weight of 10 gm suggests that many were preadolescent. There were only about 500 subjects in the young age group, too few to be sure of no effect at a low rate of tumor in- duction. The 10,000 adults give more reliable negative data. In the data analyzed by Maxon et al.4 therapeutic doses of 131I were used to evaluate the risk to the thyroid. This would be expected to give a falsely low estimate of thyroid tumors because of the propensity for eventual cell death at this dose level. The conclusion drawn from these analyses was that the risk to the thyroid from internal radiation is less than that from comparable amounts of external radiation. This is supported, at least in a qualitative sense, by earlier animal data, but a recent study of young rats'7 suggests that 131I and x ray are equivalent (Table V). There may be a species effect, however, because most of the cancers were follicular carcinomas as opposed to the papillary carcinomas most frequently found in man. From all this evidence, I think that we must conclude, first, that exposure to internal irradiation from radioiodine is surely a potential Bull. N.Y. Acad. Med. IMPLICATIONS FOR POTASSIUM IODIDE 1033

TABLE VI. SIGNIFICANCE OF A "MINOR" ESCAPE OF RADIOIODINE

Power reactor operating at 2,100 MW (thermal) 1311 content of core: 6.1 x 107 Ci 1% release + unfavorable weather (Il'in et al. 1972)18: 500 rads to child's thyroid at 75 Km 500 rads to adult's thyroid at 30 Km

Additional contribution from short-lived radioiodine: depends on time between release and exposure. hazard, and, second, that the risk estimates derived from external irradia- tion exposure are probably too high. Some other factors, however, must be considered in evaluating the seriousness of the risk. One is that the cost both to the individual and to society of irradiation-induced benign nodules is not trivial because they will require medical attention and, frequently, surgical removal. Second, we must remain cautious concerning the antici- pated severity of thyroid cancers that appear long after exposure. Until now, almost all the cancers have been papillary or follicular with very low morbidity and mortality. As the exposed cohort ages, it is not likely that the tumors will take on the attribute of those occurring in nonirradiated patients after age 50, i.e., more aggressive papillary cancers and a higher proportion of anaplastic cancers. We should soon see evidence on this point in the x-ray-exposed cohort. Now we must ask once again whether enough radioiodine could be released in a nuclear accident to place the thyroid at risk. A very minor fractional leak of radioiodine from the reactor core can deliver a harmful amount of radiation to the thyroid of a person at some distance from the source (Table VI). In this estimate, as much as 500 rads from 1311 to a child's thyroid at 75 km could result from a 1% release to the atmosphere. Despite the fortunate outcome at Three Mile Island and the new informa- tion suggesting that reaction of iodine with cesium decreases its volatility, I believe that we must assume that a significantly dangerous leak is indeed possible. What, then, is the thyroid risk at different levels of exposure? Unfortu- nately, we can say only that it is finite but impossible to define accurately. To get some feeling for a point of reference, I have applied the approxi- mate risk factors for x-ray exposure to children and the thyroid nodule and cancer incidence rates in the general population of the United States, shown in Table VII. Thyroid risks presented in Table VIII were calculated for assumed risk ratios for x ray and 13'I ranging from one, as proposed by Vol. 59, No. 10, December 1983 1034 J. ROBBINS

TABLE VII

Excess thyroid risk from x-ray exposure in children"3 Nodules (total) 10/10' PY-rad Cancers 4/10;" PY-rad Expected annual incidence of thyroid tumors in USA 19 20 Nodules 4/100/40* = IOO1/oIO Cancers 10,200/2 x 108 = 40/10' Cancer deaths 1,050/2 x 108 = 5/10"

*Based on 4% prevalence at age 40.

TABLE VIII. THYROID TUMOR INDUCTION AS FUNCTION OF DOSE AND TUMOROGENESIS RATIO OF X-RAY: "'I

Cases/JO" PY Relative risk * Ratio Rad Nodules Cancers Nodules Cancers 1 25 250 100 1.2 3 100 1,000 400 2 9 200 2,000 800 3 17 10 25 25 10 1.02 1.2 100 100 40 1.1 1.8 200 200 80 1.2 2.6 50 25 5 2 1.005 1.04 100 20 8 1.02 1.2 200 40 16 1.04 1.3

*(Excess + Expected)/Expected, calculated from parameters in Table VII. The digits beyond the decimal point are given only to portray the trends and obviously do not imply this degree of precision.

Dr. Shleien, to 50, the upper range derived from the data reviewed by Maxon et al.4 Between, there is a ratio of 10, which may be quite realistic considering the evidence, especially the failure thus far to find an in- creased thyroid risk among the 500 Swedish patients followed after ""'I exposure to between 100 and 200 rads. We should note that, if the ratio is indeed 10, and if the death rate from radiation-induced cancer is 10% (Table VII), exposure to 200 rads from 1:11 would result in eight excess deaths per 10' person-years* (from Tables VII and VIII). This is the same rate as would be expected at 25 rad if the risk ratio of x ray"'I is one.

*This is four times higher than I estimated previously2' because that estimate was made proportional to the expected increase in radiation-induced nodules rather than cancers and these do not increase in parallel.

Bull. N.Y. Acad. Med. IMPLICATIONS FOR POTASSIUM IODIDE 1035

TABLE IX. SOURCES OF EXCESS IODINE INTAKE

Source Form Amount Water purification Oxidized 2-4 mg daily Treatment of hyperthyroidism Iodide 150-300 mg daily Expectorant Iodide 300-1200 mg daily X-ray contrast Organic 5-40 g

Several studies'8'22 have conclusively shown that iodide will almost completely block the entry of 131I into the thyroid gland if given before the exposure in large enough quantity (100 mg iodine or 130 mg KI). The question of possible iodine toxicity must now be faced. Dr. Yalow believes that toxic reactions to iodide distributed to a large unsupervised population would be serious and frequent enough to warrant witholding this protective medication. My view is that the risk must be small and could be further reduced by measures I shall discuss. Let me put this iodine dose in context with other sources of excess iodine intake (Table IX). Oxidized forms of inorganic iodine used to purify water can be ingested at the rate of at least 2 to 4 mg daily for many months with no apparent ill effects.23 Iodide as a medication is used in doses up to a gram or more per day, and organic iodine compounds containing up to 40g iodine, some of which is metabolized to iodide, are given as x-ray contrast agents. Toxic reactions to the latter are not necessarily due to the iodide released. The dose range we are considering is the same as was used extensively in former years to treat hyperthyroid- ism. No systematic study of iodide toxicity at this dose, especially when given for only one to 10 days, has been carried out, but the indications are that it must be quite uncommon. 18,22,24,25 Further, in virtually every instance, the toxic effects are reversible when iodide is discontinued. Table X lists various adverse reactions to iodide observed with a daily intake of the order required to protect the thyroid. Goiter and hypothyroid- ism follow only prolonged administration25 since they result mainly from blockade of hormone synthesis rather than interference with hormone release, and the gland contains a considerable store of hormone even when it is diseased. Further, when hormone delivery to the tissues ceases, the falloff of hormone effect occurs with a half time of about two weeks. Therefore, the risk of goiter and can be ignored. In the United States, where there is no dietary iodine deficiency, iodine- induced hyperthyroidism will presumably occur only when the thyroid is

Vol. 59, No. 10, December 1983 1036 J. ROBBINS

TABLE X. FACTORS FAVORING ADVERSE REACTIONS TO IODINE

Factor Amount of iodide Reaction Genetic susceptibility 10-100 mg daily Goiter, hypothyroidism Thyroid damage 150-200 mg daily Hypothyroidism (Thyroiditis, "31I therapy) Nodular goiter 150-200 mg daily Hyperthyroidism Skin disease Exacerbation Idiopathic urticaria and 500 mg X 5* Exacerbation of urticaria. Lupus erythematosis with 1,000 mg X It Serum sickness type hypocomplementemic vasculitis hypersensitivity

*500 mg repeated five times t 1,000 mg given one time abnormal, usually when there is a preexisting nodular goiter.26 In a young, otherwise healthy individual, moderate hyperthyroidism is well tolerated, and a significant risk would be anticipated only in the presence of coexisting cardiovascular disease such as coronary insufficiency or the possibility of myocardial failure. These risks could be avoided by advising individuals with known heart disease or with known nodular goiter not to take the iodide. Certain skin diseases, such as acne and untreated dermatitis herpetifor- mis, may be exacerbated by iodide, but this would be serious only if the skin ailment were severe. Such patients also could be advised not to take iodide. The most serious risk would be the serum sickness type reaction seen in a small number of persons such as those described by Curd et al.,27 who have a rare form of vasculitis associated with hypocomplemen- temia and chronic urticaria or lupus erythematosis. Three of the four cases Curd et al.27 reported had chronic urticaria, and these also could be warned against taking iodide. A simpler approach would take into account two facts: that almost all people with a disease that sensitizes them to iodide toxicity are adults, and that the greatest danger, possibly the only danger at a low exposure level, of irradiation-induced thyroid tumors occurs in children. I believe that iodide toxicity could be essentially avoided with little if any loss in benefit to a population at risk by restricting the administration of iodide to preadolescent children and to women who are more than two months pregnant. The latter group is included because 131I is known to reach the fetal thyroid which is sensitive to irradiation effects. It is important to note that a given rad dose from 131I in a child's thyroid is produced by less in- gested isotope than in an adult's, in proportion to the size of the thyroid gland. Bull. N.Y. Acad. Med. IMPLICATIONS FOR POTASSIUM IODIDE 1037

This analysis leads me to believe that the possible induction of thyroid tumors is a significant risk following nuclear reactor accidents, that this can be prevented by administration of iodide, and that it is possible to do this safely. The remaining question is to evaluate the practicality of such a program. The monetary cost, although substantial, is surely small relative to the cost of installing and maintaining the reactors themselves, and could easily be absorbed in the cost of energy distribution. A more serious question is one of feasibility. Because of the need for early administration of the iodide in the event of an accident, predistribution is required, together with instructions such as those outlined by Wolfe et al.,28 and a predetermined plan for notification, presumably by radio, when the medi- cation should be instituted. Apparently such a system has been accom- plished in Sweden28 and should be possible everywhere, although with varying difficulty depending on population density. Plans should also be established to monitor adverse reactions to iodide to clarify the issues we have discussed today. There is no question that advance- planning should be deliberate and timely, whether the decision be to distribute iodide, to stockpile iodide for possible future distribution, or to withhold its use until more knowledge has accumulated. In my opinion we know enough to say that the distribu- tion and eventual use of iodide in time of need has merit and that an estimated triggering point of 200 rads internal radiation is a realistic point at which to balance the potential risk of irradiation-induced thyroid tumors against the potential risk of administering iodide to the population at large. It is essential to continue the observations on the cohorts exposed to diagnostic 13I1 and to organize studies of the incidence of reactions to iodide so that we can better define the requirements for protecting the thyroid from nuclear accidents.

REFERENCES 1. Starr, C. and Whipple, C.: Risks of risk 4. Maxon, H. R., Thomas, S. R., Saenger, decisions. Science 208: 1114-19, 1980. E. L., et al.: Ionizing irradiation and the 2. Ron, E. and Modan, B.: Benign and induction of clinically significant disease malignant thyroid neoplasms after child- in the human thyroid gland. Am. J. Med. hood irradiation for tinea capitis. J. Nat. 63:967-978, 1977. Cancer Inst. 65: 7-11, 1980. 5. Royce, P. R., MacKay, B. R., and 3. Shore, R. E., Woodard, E. D., Paster- Dissabella, M. M.: Value of postirradi- nack, B. S., and Hempelmann, L. H.: ation screening for thyroid nodules. Radiation and host factors in human J. A. M. A. 242: 2675-78, 1979. thyroid tumors following thymus irra- 6. Doniach, I.: Comparison of the carcino- diation. Health Phys. 38:451-65, genic effect of X-irradiation with radio- 1980. active iodine on the rat's thyroid. Br.

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J. Cancer 11: 67-76, 1957. 65: 1221-24, 1980. 7. Conard, R. A., et al.: A Twenty-Year 16a. Holm, L. E., Thyroid treatment and its Review of Medical Findings in a Mar- possible influence on occurrence of ma- shallese Population Accidentally Ex- lignant tumors after diagnostic ITI. posed to Radioactive Fallout. Upton, Acta Radiol. Oncol. 19:455-59, 1980. N.Y., Brookhaven National Laborato- 17. Lee, W., Chiacchierini, R. P., Shleien, ries Associated Universities, Inc., B., and Tellis, N. C.: Thyroid tumors 1975. following "11I or localized X irradiation 8. Larsen, P. R., Conard, R. A., Knud- to the thyroid and pituitary glands of sen, K., et al.: Thyroid hypofunction rats. Radiat. Res. 92: 307-19, 1982. after exposure to fallout from a hydro- 18. Wolff, J.: Physiological aspects of io- gen bomb explosion. J. A. M. A. dide excess in relation to radiation pro- 247: 157 1-75, 1982. tection. J. Molec. Med. 4: 151-65, 9. Walinder, G. and Sjdden, A. M.: Effect 1980. of irradiation on thyroid growth in 19. Vander, J. B., Gaston, E. A., and mouse foetuses and goitrogen chal- Dawber, T. R.: The significance of lenged adult mice. Acta Radiol. Ther. nontoxic thyroid nodules. Final report Phys. Biol. 10: 579-92, 197 1. of a 15 year study of the incidence of 10. Walinder, G., Jonsson, C. J., and Sjo- thyroid malignancy. Ann. Intern. Med. den, A. M.: Dose rate dependence in 69:537-40, 1968. the goitrogen stimulated mouse thy- 20. Cancer Facts and Figures. New York, roid. A comparative investigation of the Amer. Cancer Soc., 1983. effects of roentgen, 13'I and 1:321 irradia- 21. Robbins, J.: Iodine deficiency, iodine tion. Acta Radiol. Ther. Phys. Biol. excess and the use of iodine for protec- 11:24-36, 1972. tion against radioactive iodine. Thyroid 11. Book S. A., McNeill, D. A., Parks, N. Today 3:1-5, 1980. J., and Spangler, W. L.: Comparative 22. NCRP Report No. 55: Protection ofthe effects of iodine-132 and iodine-131 in Thyroid Gland in the Event ofReleases rat thyroid glands. Radiat. Res. of Radioiodine. Washington, D. C., 81: 246-53, 1980. Nat. Council on Radiation Protection 12. Rallison, M. L., Dobyns, B. M., Keat- and Measurements, 1977. ing, F. R., et al.: Thyroid disease in 23. Freund, G., Thomas, W. C., Bird, E. children. A survey of subjects poten- D., et al.: Effect of iodinated water tially exposed to fallout radiation. supplies on thyroid function. J. Clin. Amer. J. Med. 56:457-63, 1974. Endocr. 26: 619, 1966. 13. Rallison, M. L., Dobyns, B. M., Keat- 24. Bureau of Radiological Health and Bu- ing, F. R., et. al.: Thyroid nodularity in reau of Drugs, Food and Drug Adminis- children. J. A. M. A. 233: 1069-72, tration: Potassium Iodide as a Thyroid- 1975. Blocking Agent in a Radiation Emer- 14. Rall, J. E.: The Effects of Radiation on gency: Recommendations on Use. the Thyroid Gland: A Quantitative Washington, D. C., 1982. Analysis. In: Physiopathology ofEndo- 25. Wolff, J.: Iodide goiter and the pharma- crine Diseases andMechanisms ofHor- cologic effects of excess iodide. Am. J. mone Action, Soto, R. J., De Nicola, Med. 47:101-24, 1969. A., and Blaquier, J., editors. New 26. Fradkin, J. F. and Wolff, J.: Iodide- York, Liss, 1981, pp. 29-43. induced thyrotoxicosis. Medicine 62: 1- 15. Holm, L. E., Lundell, G., and Wa- 20, 1983. linder, G.: Incidence of malignant thy- 27. Curd, J . G., Milgrom, H ., Stevenson, roid tumors in humans after exposure to D. D., et al.: Potassium iodide sensitiv- diagnostic doses of iodine- 131. Retro- ity in four patients with hypocomple- spective cohort study. J. Nat. Cancer mentemic vasculitis. Ann. Intern. Med. Inst. 64:1055-59, 1980. 91:853-57, 1979. 16. Holm, L. E., Eklund, G., and Lundell, 28. Wolfe, S. M., Lacheen, C., and Barg- G.: Incidence of malignant thyroid tu- mann, E.: Testimony before Subcom- mors in humans after exposure to diag- mittee on Oversight and Investigation, nostic doses of iodine- 131. II. Estima- House Interior and Insular Affairs tion of thyroid gland size, thyroid Committee hearing on potassium io- radiation dose and predicted number of dide's role in emergency planning for malignant tumors. J. Nat. Cancer Inst. nuclear accident, March 5, 1982.