Effects of time of administration and dietary iodine levels on potassium iodide (KI) blockade of thyroid irradiation by 131I from radioactive fallout.

Radioiodines, particularly 131I, may be released into the environment in breach-of-containment nuclear reactor accidents and localize in and irradiate the thyroid with an attendant risk of neoplastic growth and other adverse health effects. Pharmacologic thyroid blockade by oral potassium iodide (KI) (50-100 mg in adults) can substantially reduce thyroid uptake of and irradiation by internalized radioiodine. In the current analysis, computer modeling of iodine metabolism has been used to systematically elucidate the effects of two practically important but highly variable factors on the radioprotective effect of KI: the time of administration relative to exposure to radioiodine and the dietary level of iodine. In euthyroid adults receiving iodine-sufficient diets (250 microg d(-1) in the current analysis), KI administered up to 48 h before 131I exposure can almost completely block thyroid uptake and therefore greatly reduce the thyroid absorbed dose. However, KI administration 96 h or more before 131I exposure has no significant protective effect. In contrast, KI administration after exposure to radioiodine induces a smaller and rapidly decreasing blockade effect. KI administration 16 h or later after 131I exposure will have little effect on thyroid uptake and absorbed dose and therefore little or no protective effect. The 131I thyroid absorbed dose is two-fold greater with insufficient levels of dietary iodine, 2,900 cGy/37 MBq, than with sufficient levels of dietary iodine, 1,500 cGy/37 MBq. When KI is administered 48 h or less before 131I intake, the thyroid absorbed doses (in cGy/37 MBq) are comparably low with both sufficient and insufficient dietary iodine levels. When KI is administered after 131I intake, however, the protective effect of KI is less and decreases more rapidly with insufficient than with sufficient dietary iodine. For example, KI administration 2 and 8 h after 131I intake yields protective effects of 80 and 40%, respectively, with iodine-sufficient diets, but only 65 and 15% with iodine-deficient diets. In conclusion, whether exposed populations receive sufficient or insufficient dietary iodine, oral KI is an effective means of reducing thyroid irradiation from environmentally dispersed radioiodine but is effective only when administered within 2 d before to approximately 8 h after radioiodine intake.

The Chernobyl accident and its consequences: update at the millennium.

A marked increase in the incidence of papillary thyroid cancer in children has been documented in regions of the former Soviet Union most heavily contaminated by radioactive fallout from the Chernobyl nuclear power plant accident in April 1986. Accumulation of radioactive iodines by normal iodine trapping mechanisms resulted in significant radiation doses to the thyroid gland. Although it has long been known that thyroidal radiation resulted in nuclear and chromosomal abnormalities visible by light microscopy, modern molecular biology techniques are beginning to identify much smaller alterations in chromosomal coding sequences that are associated with malignant transformation. Although stable chromosomal abnormalities can be detected in Chernobyl-associated thyroid cancers, they are much less prevalent than in thyroid cancers developing after external beam irradiation. However, several unique chromosomal breakpoints have been described in radiation-associated thyroid cancers that are not commonly found in spontaneously occurring thyroid cancer. Furthermore, activation of specific subtypes of the ret/PTC tyrosine kinase oncogene appears to be more common in radiation-associated thyroid cancers than in spontaneous thyroid cancers. In summary, thyroid cancers developing in the aftermath of the Chernobyl accident provide a unique opportunity to search for chromosomal abnormalities that may be specific for radiation-induced thyroid cancer.

A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer.

Recombinant human TSH has been developed to facilitate monitoring for thyroid carcinoma recurrence or persistence without the attendant morbidity of hypothyroidism seen after thyroid hormone withdrawal. The objectives of this study were to compare the effect of administered recombinant human TSH with thyroid hormone withdrawal on the results of radioiodine whole body scanning (WBS) and serum thyroglobulin (Tg) levels. Two hundred and twenty-nine adult patients with differentiated thyroid cancer requiring radioiodine WBS were studied. Radioiodine WBS and serum Tg measurements were performed after administration of recombinant human TSH and again after thyroid hormone withdrawal in each patient. Radioiodine whole body scans were concordant between the recombinant TSH-stimulated and thyroid hormone withdrawal phases in 195 of 220 (89%) patients. Of the discordant scans, 8 (4%) had superior scans after recombinant human TSH administration, and 17 (8%) had superior scans after thyroid hormone withdrawal (P = 0.108). Based on a serum Tg level of 2 ng/mL or more, thyroid tissue or cancer was detected during thyroid hormone therapy in 22%, after recombinant human TSH stimulation in 52%, and after thyroid hormone withdrawal in 56% of patients with disease or tissue limited to the thyroid bed and in 80%, 100%, and 100% of patients, respectively, with metastatic disease. A combination of radioiodine WBS and serum Tg after recombinant human TSH stimulation detected thyroid tissue or cancer in 93% of patients with disease or tissue limited to the thyroid bed and 100% of patients with metastatic disease. In conclusion, recombinant human TSH administration is a safe and effective means of stimulating radioiodine uptake and serum Tg levels in patients undergoing evaluation for thyroid cancer persistence and recurrence.

Evaluation of environmental, nutritional, and host factors in cats with hyperthyroidism.

The pathologic changes associated with hyperthyroidism (adenomatous hyperplasia, adenoma of the thyroid gland) have been well characterized in cats, but the pathogenesis of these changes remains unclear. In this research, we undertook a case-control study to search for potential risk factors for this disease. Owners of 379 hyperthyroid and 351 control cats were questioned about their cats' exposure to potential risk factors including breed, demographic factors, medical history, indoor environment, chemicals applied to the cat and environment, and diet. The association between these hypothesized risk factors and outcome of disease was evaluated by conditional logistic regression. Two genetically related cat breeds (ie, Siamese and Himalayan) were found to have diminished risk of developing hyperthyroidism. Cats that used litter had higher risk of developing hyperthyroidism than those that did not. Use of topical ectoparasite preparations was associated with increased risk of developing hyperthyroidism. Compared with cats that did not eat canned food, those that ate commercially prepared canned food had an approximate 2-fold increase in risk of disease. When these 4 variables (breed, use of cat litter, consumption of canned cat food, and use of topical ectoparasite preparations) from the univariate analysis were selected for further study as candidate risk factors and analyzed by multivariate conditional logistic regression, a persistent protective effect of breed (ie, Siamese or Himalayan) was found. In addition, results suggested a 2- to 3-fold increase in risk of developing hyperthyroidism among cats eating a diet composed mostly of canned cat food and a 3-fold increase in risk among those using cat litter. In contrast, the use of commercial flea products did not retain a strong association. The results of this study indicate that further research into dietary and other potentially important environmental factors (eg, cat litter) is warranted.

Thyroid uptake of liquid versus capsule 131I tracers in hyperthyroid patients treated with liquid 131I.

The amount of 131I used to treat hyperthyroid patients is based in part on the 24-hour thyroid uptake of a diagnostic amount of radioiodine (tracer). We compared the 24-hour uptake of an 131I tracer administered in liquid or capsule form to the 24-hour uptake of 131I therapy administered as liquid. Sixty-five hyperthyroid patients with Graves' disease were evaluated and subsequently treated with radioiodine. The liquid group (45 patients) received a liquid 131I tracer (1.85 MBq [0.05 mCi]) and the capsule group (20 patients) received a capsule 131I tracer (1.63 MBq [0.044 mCi]). Probe calibration factors were the same for the liquid and capsule 131I standards. All patients received therapeutic amounts of 131I [114.7-1106.3 MBq [3.1-29.9 mCi]) in liquid form. Therapy uptakes were obtained using the same collimated uptake probe modified with a calibrated lead shield to attenuate the high photon flux. The mean therapeutic uptake was the same for both groups (58%). The mean diagnostic uptake for the capsule group, however, was less than the mean diagnostic uptake for the liquid group (44% vs. 63%). The mean diagnostic uptake for the capsule group was significantly lower than the mean therapeutic uptake for this group (44% vs. 58%), whereas the mean diagnostic and therapeutic uptakes were similar for the group receiving a liquid tracer (63% vs. 58%). In conclusion, diagnostic uptakes performed with a liquid tracer more accurately predicted liquid therapy uptakes than diagnostic uptakes performed with a capsule tracer. This raises concern about the bioavailability of 131I in capsule form and has implications for determining the amount of 131I to administer for therapy. Patients whose 131I therapy was based on the uptake of a capsule tracer received a higher than intended amount of radiation to the thyroid gland.

Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group.

CONTEXT: High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic (131)I to the development of cancer, its extensive medical use indicates the need for additional evaluation. OBJECTIVE: To evaluate cancer mortality among hyperthyroid patients, particularly after (131)I treatment. DESIGN: A retrospective cohort study. SETTING: Twenty-five clinics in the United States and 1 clinic in England. PATIENTS: A total of 35 593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91 % had Graves disease, 79% were female, and 65% were treated with (131)I. MAIN OUTCOME MEASURE: Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism. RESULTS: Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86). CONCLUSIONS: Neither hyperthyroidism nor (131)I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following (131)I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, (131)I appears to be a safe therapy for hyperthyroidism.

Radioiodine and the treatment of hyperthyroidism: the early history.

Little was known about iodine metabolism in the mid-1930s, but when Saul Hertz and his chief, J. Howard Means, at the Massachusetts General Hospital (MGH) realized in 1936 that radioiodine could be made and used as a tracer, they arranged with physicists Robley Evans and Arthur Roberts at the Massachusetts Institute of Technology (MIT) to make the short-lived 128I and study its physiology in rabbits. By 1938, they showed that the rabbit's thyroid gland rapidly took up 128I, especially when there was only a little non-radioactive iodine present. There was, however, no hope of using 128I as a treatment because of its brief half-life (25 minutes). In 1939, Joseph Hamilton and Mayo Soley, working with Ernest Lawrence's cyclotron in Berkeley, California, were able to make several radioiodines; one was 130I (12-hour half-life) and another 131I (8-day half-life). They were the first to give these radioiodines to humans to study iodine physiology. The MGH-MIT group also built a cyclotron and by 1940 had generated these two new radioiodines. One of the goals of both groups was the treatment of hyperthyroidism. Hertz and Roberts were the first to do so on March 31, 1941; Hamilton and John Lawrence, Ernest's brother, began on October 12, 1941. By 1942, the United States was actively fighting in World War II. That year both Boston and Berkeley groups have preliminary data on the treatment of hyperthyroidism in Atlantic City; both showed that it was effective and went on to treat more patients. In Berkeley the therapy was viewed cautiously, and, in many case, the physicists were mainly occupied with work for the Manhattan District. In Boston Hertz used the therapy as often as he could, emphasizing the use of 130I, until he joined the U.S. Navy in 1943. Earle Chapman, a clinician on the voluntary staff of the MGH, took over Hertz's practice in 1943; their later differences over the precise treatment and who was in charge led to their falling out. After Hertz's release from the Navy he was not permitted to return to the MGH and became quite bitter; Chapman stayed on at the MGH. After the war was over, both had acquired a sufficient number of patients--there was then no such thing as a controlled trial--and wrote up the results for publication. Each wrote a different physicist, Hertz with Roberts and Chapman with Evans. When Hertz learned that Chapman's paper was being considered by the Journal of the American Medical Associations, he quickly sent his manuscript to JAMA as well. Although the editor of JAMA was puzzled by two papers on the same topic from the same institution, both papers appeared in the same issue of JAMA on May 11, 1964, and announced the new therapy was effective treatment for hyperthyroidism.

Potassium iodide for thyroid blockade in a reactor accident: administrative policies that govern its use.

A marked increase in thyroid cancer among young children who were in the vicinity of the Chernobyl nuclear power plant at the time of the 1986 accident strongly suggests a possible causal relationship to the large amounts of radioactive iodine isotopes in the resulting fallout. Although remaining indoors, restricting consumption of locally produced milk and foodstuffs, and evacuation are important strategies in a major breach-of-containment accident, stable potassium iodide (KI) prophylaxis given shortly before or immediately after exposure can reduce greatly the thyroidal accumulation of radioiodines and the resulting radiation dose. Concerns about possible side effects of large-scale, medically unsupervised KI consumption largely have been allayed in light of the favorable experience in Poland following the Chernobyl accident; 16 million persons received single administrations of KI with only rare occurrence of side effects and with a probable 40% reduction in projected thyroid radiation dose. Despite the universal acceptance of KI as an effective thyroid protective agent, supplies of KI in the US are not available for public distribution in the event of a reactor accident largely because government agencies have argued that stockpiling and distribution of KI to other than emergency workers cannot be recommended in light of difficult distribution logistics, problematic administrative issue, and a calculated low cost-effectiveness. However, KI in tablet form is expensive and has a long shelf life, and many countries have largely stockpiles and distribution programs. The World Health Organization recognizes the benefits of stable KI and urges its general availability. At present there are 110 operating nuclear power plants in the US and more than 300 in the rest of the world. These reactors product 17% of the world's electricity and in some countries up to 60-70% of the total electrical energy. Almost all US nuclear power plants have multistage containment structures with large steel and concrete shells and multiple redundancy of core cooling mechanisms. These successfully prevented the release of major amounts of radionuclides in the Three Mile Island partial loss-of-primary coolant accident in 1979. The Chernobyl accident, in a different type of reactor that is common in Eastern Europe, did not have effective outer shell containment and released almost 50 MCi of 131I compared to the 20 Ci of 131I released at Three Mile Island. Such accidents have precipitated extensive re-evaluation of the design and safety devices of all operating reactors. However, a major contributing factor to the accidents was human error and considerable efforts must be made to train plant operators so they have a better understanding of reactor operation and use of safety mechanisms.

Radioiodine and thyroid disease: the beginning.

In 1936, Karl Compton, then president of the Massachusetts Institute of Technology (MIT) and the thyroid group of the Massachusetts General Hospital (MGH), undertook a joint study that led to the production of small amounts of short-lived radioiodine (iodine 128, half-life, 25 min). The original intent was to use it for diagnosis and treatment of thyroid disease, but in order to explore the underlying physiology, their first work was performed in rabbits and published in 1938. It clearly showed that the radioiodine was selectively and avidly taken up by the thyroid gland. It was immediately apparent to the MGH-MIT group and another team working at the Berkeley, CA cyclotron that longer-lasting iodine isotopes were needed, and soon both developed procedures for cyclotron-produced 130 (half-life, 12.5 hr) and 131I (half-life, 8 d). In 1939, the Berkeley group, using 131I, was the first to show that the normal human thyroid gland accumulated radioiodine. By 1941, the MGH-MIT team, using mainly 130I, was able to successfully treat a few patients with hyperthyroidism, and so achieved their original goal. The Berkeley group did the same a few months later, using mainly 131I. Both presented results at the same meeting of the American Society for Clinical Investigation in Atlantic City, NJ in the spring of 1942. This was in the midst of World War II and it was not easy to get much 130I or 131I, so experience was limited. Although effective, radioiodine treatment of hyperthyroidism had not been widely adopted by the end of the war in 1945, partly because radioiodine remained in short supply and partly because another medical therapy for hyperthyroidism, antithyroid drugs, had been invented. However, by 1946, fission-derived radioiodine became readily available as a by-product of the Manhattan project in Oak Ridge, TN; hundreds of patients were treated within a few years, both for hyperthyroidism and for thyroid cancer. A new treatment, based on the physiological application of a radioisotope of iodine, was then a reality.

Radioiodine treatment of 524 cats with hyperthyroidism.

OBJECTIVE: To evaluate a protocol for subcutaneous radioiodine treatment of cats with hyperthyroidism in which the dose was determined on the basis of severity of the cat's clinical signs, thyroid tumor size, and magnitude of the serum thyroxine (T4) concentration. DESIGN: Prospective case series. ANIMALS: 524 cats with hyperthyroidism. PROCEDURE: A scoring system based on 3 factors (severity of clinical signs, size of the thyroid gland, and magnitude of the serum T4 concentration) was used to select the dose of radioiodine to be administered subcutaneously. RESULTS: On the basis of the scoring system, 310 (59%) cats were treated with a low dose of radioiodine (< 3.5 mCi; median, 3.0 mCi), 158 (30%) were treated with a moderate dose (3.5 to 4.4 mCi; median, 4.0 mCi), and 56 (11%) were treated with a high dose (> or = 4.5 mCi; median, 5.0 mCi). At time of discharge from the hospital, serum T4 concentration was still high in 80 (15.3%) cats, but by 6 months after administration of radioiodine, the serum T4 concentration had decreased to within or below reference range in all but 8 (1.5%) cats with persistent hyperthyroidism. Many cats had low serum T4 concentrations at some time after radioiodine treatment, but only 11 (2.1%) cats developed clinical and clinicopathologic features of hypothyroidism and required supplementation with L-thyroxine. Thirteen (2.5%) cats had a relapse of hyperthyroidism 1.1 to 6.5 years after initial radioiodine treatment. Overall, the response to treatment was considered good in 94.2% of the cats. Median survival time in the cats was 2.0 years; the percentage of cats alive after 1, 2, and 3 years of treatment was 89, 72, and 52%, respectively. CLINICAL IMPLICATIONS: Results of the study suggest that this method of dose estimation works well and that subcutaneous administration of radioiodine provides a safe and effective means of treating hyperthyroidism in cats.

Treatment of hyperthyroid disease.

PURPOSE: To evaluate treatments for hyperthyroid disease. DATA SOURCES: Selected studies published during the last 20 years addressing the diagnosis, causes, and treatment of hyperthyroid disease. STUDY SELECTION: Studies were chosen based on their usefulness in addressing specific points in the treatment of hyperthyroid disease. DATA EXTRACTION: Various treatment principles extracted from the references form the basis for the conclusions and recommendations made here. RESULTS: Hyperthyroid disease is a common endocrine disease. Although Graves disease is the most common cause of thyrotoxicosis, other primary and secondary causes exist. With classic signs and symptoms accompanied by confirmatory laboratory measures of thyroid hyperfunction, the diagnosis can be established firmly. Radioiodine is the preferred method to treat Graves disease; however, recent data concerning treatment with a combination of propylthiouracil and thyroxine require further evaluation to establish its efficacy. Radioiodine is also the preferred treatment for the other forms of hyperthyroid disease; however, patient-specific considerations in both may require patient-tailored therapies. CONCLUSIONS: Hyperthyroid disease can be treated definitively for most patients. Palliative therapy with beta-adrenergic blockade is useful in some patients. Further studies are needed to determine whether more recently described treatments have improved efficacy and whether therapy directed specifically at the underlying immunologic cause of Graves disease can be used successfully.

Radon update: facts concerning environmental radon: levels, mitigation strategies, dosimetry, effects and guidelines. SNM Committee on Radiobiological Effects of Ionizing Radiation.

The risk from environmental radon levels is not higher now than in the past, when residential exposures were not considered to be a significant health hazard. The majority of the radon dose is not from radon itself, but from short-lived alpha-emitting radon daughters, most notably 218Po(T1/2 3 min) and 214Po (T1/2 0.164 msec) along with beta particles from 214Bi (T1/2 19.7 min). Radon gas can penetrate homes from many sources and in various fashions. Measuring radon in homes is simple and relatively inexpensive and may be accomplished in a variety of ways. Although it is not possible to radon-proof a house, it is possible to reduce the level. In high radon areas, if the average level is higher than 4-8 pCi/liter (NCRP recommended level is 8 pCi/liter; EPA recommended level is 4 pCi/liter), appropriate action is advised. The shape of the dose response curves for miners exposed to alpha-emitting particles in the workplace is consistent with current biologic knowledge. It is linear in the low dose range and saturates in the high dose range. No detectable increase in lung cancer frequency is seen in the lowest exposed miners (those with exposures < 120 WLM, the relevant dose interval for most homes). Evidence for a health effect from radon exposure is based on data from animal studies and epidemiologic studies of mines. Extensive radiobiologic data predict a linear dose-response curve in the low dose region due to poor biological repair mechanisms for the high density of ionizing events that alpha particles create. However, no compelling evidence for increased cancer risks has yet been demonstrated from "acceptable" levels (< 4-8 pCi/liter).

Autonomous growth and function of cultured thyroid follicles from cats with spontaneous hyperthyroidism.

Spontaneous feline hyperthyroidism is a unique experimental model of toxic nodular goiter. To determine whether feline toxic goiter is caused by extrathyroidal stimulating factors or by the intrinsic autonomy of follicular cells, primary cultures of enzymatically dissociated follicles from 15 hyperthyroid cat goiters and from 3 normal cat thyroid glands were embedded in collagen gels. Growth and function in chemically defined media were assessed by autoradiography after double labeling with 3H-thymidine and 131I-Na. Iodine organification in follicles from normal glands was TSH dependent, but intense radioiodine organification occurred in follicles from hyperfunctioning goiters even in the absence of TSH. Similarly, twice as many follicular cells of hyperfunctioning thyroid tissue, maintained without TSH in the medium, were labeled after exposure to 3H-thymidine than in follicles from normal glands. The results strongly suggest that intrinsic alterations of cell function lead to autonomy of follicular growth and function and subsequently to the development of hyperplastic nodules, causing thyrotoxicosis. The reason for the focal nature of the disease remains an unresolved challenge. Further investigation using this model may further understanding of the growth of autonomous endocrine tumors.

Comparison of technetium-99m and iodine-123 imaging of thyroid nodules: correlation with pathologic findings.

Three hundred and sixteen patients with solitary or dominant thyroid nodules were imaged both with technetium-99m- (99mTc) pertechnetate and iodine-123 (123I). The images were preferred, but differences were small and in 27%-58% of the cases there was no difference in quality between the two radionuclides. Discrepancies between 99mTc and 123I images were found in 5%-8% of cases, twice as often in multinodular goiters as in single nodules. Cytologic/histologic examination was performed on all nodules but no correlation was found between the pathology and the type of discrepancy. Twelve carcinomas were found (4%) but none in nodules showing a discrepancy. There was great variation among the observers about the preference for radionuclides and about the existence or type of discrepancies. The slightly better overall quality of 123I scans is probably not of diagnostic significance and does not justify the routine use of 123I instead of 99mTc. Routine reimaging of 99mTc hot nodules with radioiodine for cancer detection does not appear to be necessary.