Document mRVYVGo1vQ8wdJdweZwExQp0

HFM -003513 was thought to cause acute respiratorydistress and sudden death. Duffy and Fitzgerald*1 made the important observa tion in 1950 that more than one-third (36 percent) of children with papillary and follicular carcinomas of the thyroid had received radiation therapy to the upper mediastinum or neck. Subsequent publi cations in the United States reported that from one-third to three-fourths of all children and young adults with benign and malignant thyroid neoplasia received prior irradiation to the head, neck and/or me diastinum during the first five years of life. 6J-69 in a recent publication from Israel by Modan et al.,7the risk of thy roid cancer was significantly enhanced in children 12-23 years after receiving X-ray epilation treatment of the scalp for tinea capitis. In New York City, Shore, Albert and Pasternak71 observed an increasing, incidence ofthyroid adenomas 15-30 years after X-ray epilation for tinea capitis. Radiation-induced thyroid cancer may be characterized. by multi-focal malignant lesions. It is evident from all. such studies that irradiation to the thyroid in infants, chil dren and young adults up to 20 years of age carries a far greater risk of inducing neoplasia than does similar exposure in adults. This increased risk is probably due .to the1 far greater rate of mitosis in the young thyroid and, as a consequence, the greater likelihood of inducing cytogenetic abnormalities in viable cells. Hempelmann and co-workers72 noted that following irradiation of the thymus in infancy, the incidence of thyroid cancer in women 15-29 years of age increased five times over that of the rest of the irradiated population. In contrast, the incidence of thyroid cancer in irradiated women young er than age 15 or older than age 30 years was almost identical with that found in the irradiated men. The age period 15-29 years coincides with the onsetof ovulatory men strual cycles and maximal reproductive activity. During pregnancy, the thyroid gland frequently undergoes physiologic hypertrophy, presumably secondary to an increased renal loss of iodide and height ened secretion of thyroid-stimulating hor mone..In areas of endemic goiter second^ ary to low dietary intake of iodine, the' prevalence of thyroid hypertrophy during gestation is further enhanced. These observations are particularly pertinent when we recall that in animal experimen tation, increasing amounts of thyroid? stimulating hormone after radiation exposure are associated-with an increasing incidence of thyroid cancer. On the assumption of- linearity in the dose-response curve, the National Acad emy of Sciences has estimated that the risk of thyroid cancer developing in irra-* diated children- was within die range of 1.6-9.3 cases/year/million exposed chil-dren/rem.73 (In terms of biologic damage, the rem is equivalent to 1 rad of 250 KVP X-rays.) The assumption of linearity was questionable under 20-50 rads-until Mo-.. dan's study which suggested a mean ex posure dose to the thyroid of 6.5 rads. . In terms of a clinical approach to en suring early diagnosis, all children aid young adults who have had X-ray treat ment to the chest, neck, faceor scalp shoirid be kept under continuing surveillance. The thyroid gland, cervical lymph nodes and salivary glands should be examined meticulously. When there is a history of irradiation and particularly when palpable. thyroid disease is suspected, the clinical examinationshould berfellowed by a thy roid scan using 9901 Technetium pertechnetate. The 99111 Tc thyroid scan delivers 0.1 rad to the adult thyroid, as compared with the '311 scan which delivers. 100-200 rads. Although information on past X-ray exposure may not be known by a young patient, nor readily volunteered by parr ents, the.examining physician should pur sue any uncertain'aspect of the past medi cal history by securing copies of pertinent medical records. The optimal therapeutic approach to the young adult with no currently detect able abnormality but with a past history of irradiation is less clear. The efficacy of thyroid hormone to suppress thyroid stim ulating hormone (TSH) in preventing malignant neoplasia is unproven although: suppressive therapy has been used in the evaluation of a thyroid nodule.74 *00) 0910 CA-A CANCER JOURNAL FOR CLINICIANS The tumorigenic effect of irradiation on the thyroid has also been documented through a prospective study by the Atomic Bomb CasualtyCommission and the Japr anese National Institute ofHealth (ABCCJNIH). The ABOC-JNIH Adult Health- Study Program commenced in 1958 and includes standardized biennial medical examinations of about 20,000 persons selected from the 1950 cohort of 109,000 atomic bomb survivors. Prior to 1955',excessive mortality due to -leukemia was the only evidence of radiation carcino genesis among the atomic bomb survivors. When compared with a risk of 1.0 in age and sex-matched controls with little or no exposure, the relative risk of clinically, diagnosed thyroid cancer in the high ex posure subgroup was increased signify candy to 5.0 m women and 9.4 in men. Whereas the relative risk of clinically ap parent thyroid cancer in men who were exposed within 2,000 meters from.the hypocenter of the. bomb explosion was increased significantly only during the examination period 1958-1962, the risk in women with similar exposure continued to be excessive, even after 25.years of fol low-up. The cumulative risk of thyroid cancer was highest in subjects who were under 20 years of age in 1945 and were exposed to at least 50 rads of gamma and neutron radiation.7S-76 There have been isolated case reports of thyroid cancer occurring between four and 12 years after 1311 therapy for thyro toxicosis.77 A prehminary analysis of the Cooperative Thyrotoxicosis Follow-up Study indicated that theintidence of thy roid cancer or leukemia was not signifi cantly different between 22,000 patients treated with mi and 14,000 patients treat ed with surgery or antithyroid medica tions.78 In this comprehensive study, the mean follow-up time was 15 years, and most of the patients examined were over 40 years of age when first treated. The report conduded that children and young adults treated with lower dose mi therapy for hyperthyroidism appeared more sus ceptible to the development of adenomas. Higher ablative doses of5,000-10,000 rads of mi will lead to a higher inddence of of thyroid parenchyma which may predude all replication and tumorigeaesis. Since the latency period for radiationinduced thyroid cancer may be as long as 20 to 40 years, the final chapter on the treatment of thyrotoxicosis in children with radioactive iodine has not yet been written. In 1954, the population of the Rongelap Atoll in the Marshall Islands wds 'ex posed to radioactive fallout from a ther monuclear bomb.79The inhaled and in gested beta - and gamma radionuclides induded the short-lived isotopes of.radio activeiodinewhichresulted in an estimated exposure dose to the thyroid-.of between 700-1,400 rads in children and 220-450 rads in adults. The highest incidence of benign and malignant thyroid nodules Was recorded clinically in the heavfly exposed groups whowere under 10 years old at the time of exposure. The annual inci dence of thyroid cancer was estimated to be 2.1 per million children per rad. Thyroid and Breast Cancer-- la There a Common Etiology? In a review of the Connecticut experience between 1935-1964, Schoenberg8*) failed to observe a statistically significant inr crease in the incidence of thyroid cancer in breast cancer patients. Therisk Ofbreastcancerwas increased 1.8 times to expecta tion in thyroid cancer patients, but this was not determined to be statistically significant. During the brief interval of. follow-up obtained in the Third United States Can cer Survey (1969-1971), the inddence of histologically diagnosed thyroid cancer was increased significantly in women with breast cancer, but the converse relation ship, i.e., an increased incidence ofbreast cancer in women with thyroid cancer, was not observed.81 In a survey ofmultiple primary cancers at Memorial Sloan-Kettering Cancer Center, Schottenfeld and Berg observed that the incidence of clinically diagnosed pap illary and follicular thyroid carcinomas in 9,792 women with previously diagnosed breast cancer was 0.2 per year per 1,000 VOL 28, NO. 2 MAHCH/APRIL1978 8001 091i I