VIEWS: 49 PAGES: 7 POSTED ON: 5/8/2011
Exposure to Radioactive Iodine- 13 1 for Scintigraphy or Therapy Does Not Preclude Pregnancy in Thyroid Cancer Patients Martin Schlumberger, Florent De Vathaire, Claudia Ceccarelli, Marie-JoÃ«lle Delisle, Cecilia Francese, Jean-Etienne Couette, Aldo Pinchera and Claude Parmentier Department ofNuclear Medicine and Unite U351 INSERM, Institut Gustave-Roussy, Cedex, France; Institute of Endocrinology University ofPisa, Pisa, Italy; Institut Jean Godinot, Reims, France; Institut FranÃ§ois Baclesse, Caen, France miscarriages, congenital abnormalities and malignancies in Radiation is known to be mutagenic.The aim of the present study offspring, remains to be clarified in humans. In an extensive was to ascertain whether exposureto 1311 inducesgenetk@ damage, study of Japanese atomic bomb survivors, no statistically as assessed by pregnancy outcomes and the health status of offspring of women previouslyexposed to 1311 uring thyroid carci d significant effects were found (5â€”7).Moreover, no evidence of noma treatment. Methods Data on 2113 pregnancies were ob any significant genetic effect was found in two large studies of tamed by interviewing female patients treated for thyroid carcinoma pregnancy outcomes and offspring of cancer patients who had who had not received any significant external radiation to the been submitted to abdominal irradiation during childhood or ovaries. Results: The incidence of miscarriages was 11% before adolescence (8â€”10).At variance with these data, an association any treatmentfor thyroid cancer this number increasedslightlyafter between paternal preconception radiation exposure and in surgery for thyroki cancer, both before (20%) and after (20%) 1311 creased risk of leukemia in offspring has recently been reported but did not vary with the cumulative 131@ dose. Miscarriages were (11). more frequent (40%) in the ten women who were treated with 131l A high proportion of young patients with thyroid carcinoma [meandose: 3.8 GBq (108 mCi)]during the year precedingconcep are cured after surgery and appropriate treatment with radio tion. Incidencesof stillbirth, preterm birth, low birth walght, congen ital malformation and death during the first year of life were not iodine (2, 12â€”15).Control of metastatiÃ§ disease may require significantly different before or after 1311herapy. The incidence of t several courses of 13II treatment, resultipg in a cumulative dose thyroid diseaseand nonthyroidalmalignancywas similar in children of hundreds of mCi (16, 17). These patients may provide an born either before or after their mothers were exposed to 1311. appropriate model for the study of the genetic effects of Conclusion: With the exception of miscarriages, there is no evi radioiodine. dence that exposure to radioiodine affects the outcome of subse Data on the genetic effects of 1311therapy in thyroid disorders are quent pregnancies and offspring. The question of whether an scant. Studies on pregnancy outcomes and Qffspring among patients increased incidence of miscarriages within 1 yr of 1311 administration treated with 1311for thyrotoxicosis (18â€”20) or thyroid carci relates to gonadal irradiation or to insufficient control of hormonal noma (21â€”27) failed to reveal any significant 1311 related thyroid status remalnsto be established. effects. The value ofthis observation, however, is limited, given Key Words iodine-131 ; pregnancy outcome the small size of the series under study and the lack of internal J Nuci Med 1998;37606-612 controls. In the present study, the question of whether, and to what Iisused inthe and treatment Iodine-l3 widely diagnosis of extent, radioiodine administration has any significant genetic effect in humans was evaluated in a large series of women with thyroid diseases (1,2). The notion that radiation is mutagenic and may affect germ cells (thereby resulting in genetic damage thyroid cancer, who were previously submitted to diagnostic to offspring) has raised concern regarding the use of radioiodine by and/or therapeutic doses of I31 @, assessing the outcomes of in the management of thyroid disorders in patients during their pregnancy and the health status of their children. Pregnancies childbearing years. occurring before differentiated thyroid carcinoma treatment The radiation dose delivered to the ovary is approximately were used as internal controls. 0.14 cGy after administration of 37 MBq (1 mCi) 1311 in normal subjects (3 ). After surgical removal of the thyroid, PATiENTS AND METhODS thyroid cancer patients may receive diagnostic doses of I31! Data Cciiec@on ranging from 37 to I 85 MBq (1 to 5 mCi) and therapeutic doses Unselected female patients with a history of differentiated ranging from 1. 1 to 5.5 GBq (30 to 150 mCi) or more. Under thyroid carcinoma were interviewed by trained data managers these circumstances the radiation exposure for any given dose between February 1990 and December 1993. Interviews of male of 13II may be higher, since functioning metastases may be in patients are currently in progress. Of the 2573 female patients close proximity to the ovary, and patients may exhibit hypo treated at the participating centers, 376 ( 15%) died, 3 18 (12%) thyroidism at the time of radioiodine administration. This were lost to follow-up, two (.07%) refused to be interviewed and condition decreases renal iodine clearance, resulting in pro I877 (73%) were interviewed. Interviews were conducted at the longed gonadat exposure (4). time of annuat evaluation among 996 female patients at the Institut The relevance of the mutagenic effects of radiation on germ Gustave-Roussy (IGR), Villejuif, France; 235 patients at the cells as assessed by untoward pregnancy outcomes, such as Institute of Endocrinology of the Univetsity of Pisa, Italy; 583 patients at the Institut Jean Godinot, Reims, France and 63 patients at the Institut FranÃ§oisBaclesse, Caen, France. This inclusion ReceivedJan. 23, 1995;revisionaccepted Jul. 29, 1995. For correspondence or reprints contact Martin Schlumberger, MD, Department of method was reliable, given that patients with differentiated thyroid NudearMed@ne, 94805â€˜Iillejuif France. c@edex, carcinoma are evaluated at yearly intervals. No selection criteria 606 OFNUCLEAR THEJOURNAL â€¢ 37 . No. 4 . April 1996 Vol. MEDICINE TABLE I Pregnancies and Induced Abortions as a Function of Radioiodine Exposure at of concepbon(yr) socioeconomic intake (%)Before FactorNo. abortions(%)Age (meanÂ± pregnanciesInduced s.d.)Low status(%)Aicohol (%)Smoking habit (9)212(12)After any treatment1770174 (10)27 (Â±6)276 (16)156 surgery thyroidcancer34371 for (21)43(13)Cumulative (21)30 (Â±6)42 (12)72 activityof (MBq)before 1311 conception s.d.)08519 (meanÂ± (16)8(9)<370 (22)29 (Â±5)14 (16)14 (85Â±67)12225 (26)23(19)370â€”3700 (20)30(Â±6)13 1)32 (1 (2035 925)4010 (5)3(8)>3700Â± (25)30 (Â±5)3 (8)2 (8103Â±5772)9617 (25)9(9)Activity (18)30 (Â±5)12 (13)24 of 1311 dunngyear beforeconception s.d.)024745 (MBq)(meanÂ± (20)33(13)<370 (18)30 (Â±6)28 1)49 (1 (78Â±56)7616 (24)9(12)370 (21)29 (Â±6)12 (16)18 (3493Â±962)2010 (50)29 (Â±6)2 (10)5 (25)1 (5) including age, were used; the interviews lasted 20â€”60mm and 9 (ICD-9) rubrics (30). Later deaths, thyroid diseases and tumors at included questions on each pregnancy, possible complications and other sites were recorded for liveborn children. outcome, as welt as questions on marital and socioeconomic status, Data analysis took into account both the whole series of medical history, smoking habits, alcohol intake and use of medi pregnancies and the subgroup of the first series of pregnancies, cations during pregnancies. since the outcomes of multiple pregnancies in a given mother are Information on all types of radiation exposure, including radio often interdependent. iodine (activity and day of administration), radiographs and exter nal radiotherapy, was obtained from medical records. Data Validation A pilot study was performed on I 16 pregnancies in various Patients obstetric hospitals. The response rate was 90%; the information Patients were treated for differentiated thyroid carcinoma ac provided on events related to pregnancies by interviews proved to G cording to standard protocols (12,28). After surgery, 1.2â€”3.7 Bq be virtually correct all the time. It is noteworthy that only reported (30â€”100mCi) of radioiodine were administered to all patients in data could be taken into account and that early abortions not Pisa (27) and to patients with residual neoplastic tissue or with recognized as such were not included in the present analysis. poor prognostic indicators in Villejuif (12), Reims and Caen. Fifty-six of the 6 1 major birth defects identified from maternal Whole-body â€˜@â€˜Iscanning, using 37â€”185MBq (1â€”S mCi) was interviews were confirmed by medical reports obtained from performed each year for the first 2 yr and every 5 yr thereafter. obstetric hospitals; thyroid diseases and malignancies at other sites Chest radiographs were obtained routinely at the time of the in children were also confirmed by clinical examination of the @ whole-body â€˜I scan, and bone radiographs were obtained only in children and/or histological review of the diagnosis. patients with clinical or scintigraphic suspicion of bone involve ment. In patients with distant metastases or local recurrence, the Data Analysis 1311 treatment dose was 3.7â€”5.5 GBq (100â€”150 mCi). This was To study the association between the radioiodine dose and the repeated every 4 to 12 mo, until any signs of significant uptake occurrence of adverse events, a Poisson distribution was assumed disappeared. Although patients were advised not to become preg for the observed number of events and data were analyzed with the @ nant for 1 yr after I administration, more than one-third of the AMFIT computer program (31,32). Results were verified using conceptions occurring after radioiodine administration were re logistic regression analysis (33 ). The significance of the relation corded during this period of time. Most of these conceptions ships was established using the score test (33 ). Pregnancies @ occurred after a diagnostic â€˜I whole-body scan, at a time when occurring before any administration of radioiodine were used for patients were informed that there was no detectable residual the unexposed group for these calculations. disease (Table I). The expected numbers of thyroid and other cancers among All patients were given L-Thyroxine (LT4) treatment at a mean tiveborn children were estimated using PYRS software (34), which daily dose of 2.4 p.g/kg. Since the availability of TSH measure resulted in standardized incidence ratios (SIRs). SIRs express the ments in 1972, the serum TSH level was measured 4 mo after the ratio between observed and expected numbers of cancers. Calcu initiation of LT4 treatment and yearly thereafter. Moreover, the lations were stratified based on sex, age and calendar period. Data daily dose of LT4 was adjusted to suppress TSH secretion. A from French cancer registries were used as a reference (35 ), given hormonal evaluation, including serum TSH level, was performed that the incidence of cancer below age 40 is similar among most during the third month of pregnancy and, when necessary, the LT4 countries. daily dose was increased until the end of pregnancy to ensure We were unable to compare the observed number of deaths suppression of TSH secretion. during the first year of life to the expected number from external Parameters Studied statistics because the definition of a stillbirth varied among The following features were recorded for each pregnancy: countries during the study period and because it was not possible to induced abortion, miscarriage, stillbirth, prematurity (defined as a match information obtained from the interviews with legal defini gestational age below 37 wk), birth weight below the 10th tions. The expected number ofdeaths among children after the first percentile for the gestationat age (29), congenital abnormality and year of life was computed using French national data and yielded death during the first year of life. Congenital abnormalities were standardized mortality ratios (SMRs), which express the ratio defined on the basis of the International Classification of Diseases between the observed and expected numbers of deaths. During the PREGNANCY AND RADIOIODINE . Schtumberger et at. 607 TABLE 2 Untoward Outcomes of 2113 Pregnanciesas a Function of Risk Factors Other than Radiation History at the Time of Pregnancy Induced t@rth No.of abortions M@cafflages <37 wk weights <1 yr (%)AgeFactor Pregnancies (%) (%)*Stillbirths (%)@Ljvebir@,stTerm (%)Death (%)Malfomiation (%)Low at conception >35 yr 231@381033<35yr 261 24@ 1852 10 11 Smoldnghabft 1No Yes 255 27@ 122 25 710 141 24 12251014Alcohol 1840 9 intakeYes 13171421No 228 22@ 12251014Socioeconomic 1869 10 statusLow 123616@24Notlow 318 10 1326914* 1634 12 Per@itage of pregnancies, excluding those ending by induced abortion. t Percentage of livebirths. * Birth walght balow the 10th percentile for the gestabonal age (29). @ 0 p < 0.05; p < iO-@. study period, this death rate in the general population was similar pregnancy (such as anti-depressive drugs and beta-blockers) in France and in Italy. and socioeconomic status were considered. Low socioeconomic status was defined on the basis of the International Classifica RESULTS tion of Professions (38). Classifications 520â€”599, 610â€”640, Of the 1877 women interviewed, 1565 (83%) became preg 710â€”839, 870â€”874, 890â€”910, and 930â€”939 950â€”958 were nant at least once and 4766 pregnancies in total were recorded. included. In the absence of a defined profession of the patient, Among the 3 12 women who did not become pregnant, only 118 that of the husband was taken into account. had a partner, 42 of whom tried unsuccessfully to get pregnant. As reported in Table 2, induced abortions were more frequent The reasons for infertility were not investigated. No chemother in women over 35 yr and in those who did not avoid alcohol apy was administered before any pregnancy. The 2528 preg intake or smoked during their pregnancies (j < 0.001). Mis nancies which occurred before 1970 were excluded from the carriages occurred more frequently in the older age group (p < analysis since adequate validation of the reported information 0.001) and low birth weights occurred more frequently in the was not obtainable in the majority ofthese patients. Ofthe 2238 low socioeconomic group (p < 0.05). None of the medications remaining pregnancies, 125 were excluded because of previous studied had a significant influence on the pregnancy outcomes radiation exposure to sources other than 131!:32 after therapeu (data not shown). tic external irradiation to the neck for thyroid carcinoma and 93 after abdominal or pelvic radiographs unrelated to thyroid Induced Ab@on carcinoma. These pregnancies were excluded because the dose A total of 245 induced abortions was reported (Table 1). Of delivered to the ovaries during external radiotherapy to the neckthese, 174 occurred before any treatment, 19 after thyroid was estimated to range from 10â€”20 cGy (36) and from surgery and 52 after both thyroid surgery and exposure to 131!. 0.08â€”0.8 cGy per radiographic examination (37), which is of Induced abortions were more frequent after surgical treatment, @ the same order ofmagnitude as the dose delivered to the ovaries both without or after a @I dministration, but there was no after 13II administration for diagnostic purposes. correlation with the cumulative dose of 131! A higher frequence The remaining 21 13 pregnancies, registered in 923 women, of induced abortions, however, was observed among the 20 were included in the study; 1770 pregnancies occurred before pregnancies which occurred in the patients who had received any treatment for thyroid carcinoma, 85 occurred in patients therapeutic doses of 131![more than 370 MBq (10 mCi)] during who had undergone surgery for thyroid carcinoma and had not the year which preceded the conception (p < 0.001). Among received radioiodine and 258 in patients who had received these 20 pregnancies, eight occurred 6 mo or less after radio radioiodine. Among patients who were treated with 3.7 GBq iodine administration, resulting in six induced abortions and (100 mCi) radioiodine, 5 1 received one treatment, 32 received two miscarriages. Twelve pregnancies occurred more than 6 mo two, 9 received three, 5 received four, 1 received five and 2 after the radioiodine administration and resulted in four induced received six treatments, respectively. The mean time interval abortions and two miscarriages. Seven of these ten induced between last treatment and conception was 26 mo (range 0â€”222 abortions were performed to prevent a feared negative outcome; mo). No progression of thyroid carcinoma as assessed by reasons for the other three abortions were not specified. follow-up data obtained during pregnancy (clinical examination The following parameters were studied after exclusion of and Tg determination on LT4 treatment), was observed in these pregnancies which ended by induced abortion. women during pregnancies and in the subsequent period (I 4@ Miscarriages and Stillbirths. One hundred and seventy-nine TBS and Tg determinationoff LT4 treatment). miscarriages (1 1%) were observed in the 1596 pregnancies Factors other than radiation history that may have influenced which occurred before any treatment. Miscarriages were more the outcome of the pregnancy were taken into account. Age, frequent (19%) in the pregnancies which occurred after treat smoking habits, alcohol intake and use of medications during ment for thyroid cancer. As indicated in Table 3, however, such 608 OFNUCLEAR THEJOURNAL â€¢ 37 â€¢ 4 . April 1996 Vol. MEDICINE No. TABLE 3 Outcome of Pregnanciesas a Function of RadioiodineExposure, ExcludingThose Ending by Induced Abortion StillbirthsFactor No. of Miscarriages %Before pregnancies No. % No. anytreatment 2After 1596 179 11 27 surgeryfor 1Cumulativethyroidcancer 272 53 19 4 activityof 1311 conception0 (MBq)before 4<370 66 13 20 2 3370-3700 97 19 20 2 0>3700 30 3 10 0 0Activity 79 18 23 0 of duringtheyearbeforeconception (MBn)01311 2<370 202 36 18 4 0370 60 13 22 0 0an 10 4 40 0 increase was unrelated to the cumulative activity of I3Il theadministered from 1 to 20 yr. This was not different from that observed in 1%).miscarriagesbefore conception. In fact, the frequency of general population (SMR = 1.3, 95% CI: 0.7%â€”2. Ofafter was 20% in the 66 pregnancies which occurred Sixty-one liveborn children presented with malformation. surgery, but without any previous exposure to radioactive hadiodine. these, four were born of an exposed mother: two children hipWhen pyloric stenoses, one had esophageal atresia and one had a awas exposure during the year which preceded conception luxation. Their mothers were exposed before conception to taken into account, the frequency of miscarriages increased cumulative dose of 7.9, 4.8, 1.8 GBq and 222 MBq of from 18% in women who did not receive any 131! during that radioiodine, respectively. Table 5 shows the distribution of year to 40% in the ten women who were submitted to a 131I asadministration these observed malformations. Some specific diagnosis, such during the same year of the conception. Despite an undescended testicle, skin tags and birthmarks, were ex (rangedifference the small number of observations in the latter group, the cluded. Mean follow-up of the offspring was 12.7 yr yr).ship was significant (95% CI: 10%â€”70%).This relation- 0â€”23 remained significant after stratification based on the Thyroid diseases were observed in 16 children. Their distri autoimmunelative mother's age at conception and after adjustment on the cumu- bution is illustrated in Table 6. Two children had dose goiter,vious of radioactive iodine administered during the pre- hypothyroidism, one had Graves' disease, four nontoxic years. carcinomaTable eight benign adenoma and one differentiated thyroid 3 weregroups. also reports the stillbirths in treated and untreated at an age of 16 yr. Twelve children with thyroid disease No difference was found between the two groups. mother.Livebirths. born of an unexposed mother and four of an exposed in1599 Table 4 reports the following characteristics ofthe There was no significant increase in thyroid diseases, and athe livebirths: sex, prematurity, low birth weight, death during particular in cancer, among children born subsequent to first year radiation.and of life, later death, malformation, thyroid disease mother's exposure to nonthyroidal malignancy. None of these parameters ap- otherpeared Six children (1%) developed malignant diseases at sites to be 5â€”230exposure.changed by previous surgery or radioiodine than the thyroid gland at a mean age of 115 mo (range: leukemia923 These data were confirmed by the study on the first mo). These malignancies were: lymphoma in two and pregnancies. developedTwelve in four. Only one child born of an exposed mother 20first children born of unexposed mothers died after the leukemia. The cumulative incidence of cancers at the age of year of age, leading to a cumulative death rate of 0.94%, mo, CI:TABLE including the thyroid carcinoma, was 0.7% (95% 4Outcome ExposureTerm of 1599 Uvebirths as a Function of Radioiodine atNo. Lowbirth Death Death Thyroki Cancer siteFactor of <37 wk weght <1 yr 1 yr MalfOrmatiOn d@ease another (%)Before Livebirths girls(%) (%) (%)* (%) (%) (%) (%) anytreatment 6(1)After 1384 680(49) 76(5) 150(1 1) 21(2) 1 57(4) 12(1) surgery forthyroidcancer (1)Cumulative 215 97(45) 15(7) 16(7) 2 (1) 0 6 (3) 4 (2) 1 activityof (MBci)before 1311 conception0 0<370 51 29 (49) 3 (6) 3 (6) 0 0 2 (4) 0 (1)370â€”3700 76 41 (54) 6 (8) 9 (12) 2 (3) 0 1 (1) 3 (4) 1 0>3700 27 12(44) 1(4) 0(0) 0 0 1(4) 1(4) 0Activity 61 19(31) 5(8) 4(7) 0 0 2(3) 0 of 1311uringthe d yearbefore (MBq)0 conception (1)<370 162 79 (49) 12 (7) 10 (6) 2 (1) 0 6 (4) 3 (2) 1 0370 47 16 (34) 2 (4) 5 (11) 0 0 0 1 (2) 0*BfreJ, 6 2 (33) 1 (17) 1 (17) 0 0 0 0 for age(29). weightbelowthe 10thpercentile thegestational PREGNANCY AND RADIOIODINE . Schlumberger et at. 609 TABLE 5 email@example.com%). The relative risk was 2.1 (95% CI: 0.8%â€”4.3%) Classificationof 61 Congenital MalformationsObservedAmong when compared to the expected number of cancers from French 1599 UvebomChildren* cancer registries. No association was observed between the occur exposure rence of a malignancy and that of a congenital abnormality. radiotodine(ICD-9 malformationsNo. Congenital to ofPrevious code)malformations(MBq) DISCUSSION Neuralubedefects(742) t Radiation is a known mutagen. Current information on the Hydrocephalus 1 mutagenic effects of radiation on germ cells is based mainly on Mencephaly 1 0 experimental evidence in animals since only scant data are Hemiparesia 10 01 available in humans (39). Some studies have suggested an Anomalies f eye(743) o association between occupational exposure to ionizing radiation Cataract received by fathers and an increased risk of congenital abnor Glaucoma 2 0 malities (40) and leukemia (11 ) among their offspring. Exten Other 10 000 sive studies on the survivors of the atomic bombs in Japan Momahesof ear,faceandneck(744) (5â€”7)and of childhood or adolescent cancer survivors who had Deafness received radiation to the abdomen or pelvis (8â€”10), however, Heartdefects (745-746) have failed, so far, to provide any clear evidence of increased Tetralogy of Fallot germ celt mutation subsequent to exposure. Cardiaceptal s defect 4 0 In the present study, radioiodine was the only identified Other 01 medical source of gonadal irradiation after the diagnosis of Anomaliesof respiratorysystem (748) thyroid carcinoma, since pregnancies after external irradiation Collapsed lung or radiographs of the abdomen or pelvis were excluded. Chest Cleftpalate(n = 1)andcleftlip (n = 1) 20 0 radiographs were the only radiographs routinely performed (749) during the follow-up of these patients, but the estimated dose of Anomaliesof the digestivesystem radiation to the ovaries per chest radiograph is as low as 0.006 (750â€”751) cGy (37). Furthermore, factors other than radiation history that Oesophageal atresia 222 may influence the outcome of pregnancy were taken into Gastroschisis 2 0 Pyloric stenosis 6 0 (4),4810,7881 account for the analysis of I31I-related effects. With the exception of miscarriages, our data do not indicate Anomaliesof genitalorgans (752) Hypospadias 3 0 any increase in the untoward outcome of pregnancy associated with radioiodine exposure, even after administration of large Anomaliesof uhnarysystem (753) 5 0 cumulative activities. This observation is consistent with pre Bladderdysfunction Ureterobstruction 2 0 vious studies on smaller series (18â€”27). Other 1 0 The incidence of miscarriages increased when radioiodine Musculoskeletal abnormality754-755) ( was administered during the year which preceded conception Polydactyly,syndactyly 5 0 and increased further with higher radioiodine activities received Hipdysplasia 10 0 (9),1776 during that year. The eight pregnancies that occurred within 6 mo Talipesequinovarus 2 0 after the last administration of a therapeutic dose of radioiodine Legatrophy 1 0 resulted in six induced abortions and two miscarriages. This Patellaanomaly 1 0 relationship was not linked to the cumulative dose of 131! Thoracicanomaly 1 0 administered previously and remained significant after adjust Othere 2 0 ment of factors such as the mother's age (over 35). The Down's syndrome(758-0) 1 0 contribution of other factors cannot be excluded, as suggested Marfan'ssyndrome (759-8) 1 0 by the increase in miscarriages observed in patients who had undergone surgery for thyroid carcinoma and became pregnant * Numbers in parentheses are ICD-9 code. Four malformations occurred before any exposure to 13II. A possible explanation for this afterexposure radiolodine. to finding is an inadequate control of the thyroid hormonal status TABLE 6 Thyroid DiseasesAmong 1599 Livebirthsas a Function of RadioiodineExposure no. of thyroki thyroid carcinomaBefore FactorUvebirthsTotal goiterBenign diseaseEuthyrold noduleDifferentiated diseasesHypothyroldismGraves' any treatment13841220460After surgery thyroid for cancer215401021Cumulative activityof 1311 (MBq)before conception051000000<37076300021370â€”370027101000>370061000000Activity of 131@ (M@)duringtheyearbefore conception0162300021<370471010003706000000 610 OFNUCLEAR THEJOURNAL â€¢ 37 â€¢ 4 . April 1996 Vol. MEDICINE No. following thyroidectomy. LT4 treatment was instituted at sup iodine exposure remains to be established. In fact, it might welt pressive doses in all patients, and the administration of exces be related to an abnormal thyroid hormonal status. On the basis sive doses of LT4 at some stages of the pregnancy cannot be of the present study, we would recommend postponing concep ruled out. Particularly relevant for the higher incidence of tion for 1 yr after therapeutic administrations of radioiodine a miscarriages during the first year following 13â€˜I dministra until control of the thyroid hormonal status has been achieved. tion is the possible failure to control the hypothyroid status rapidly, since this was the condition for â€˜@I! administration. ACKNOWLEDGMENTS After radioiodine administration, the primary sources of radia We thank E. de Ia GenardiÃ¨refor conducting the interviews at tion to the ovaries are the blood, bladder, gut and 13II uptake in the Institut Gustave-Roussy, C. Loge for secretarial assistance and metastases close to the ovaries. Mathematical models which take L. Saint-Ange for editing the manuscript. We also thank P. into account the individual morphology ofthe patient lead to ovary Bouchard, C. Challeton, H. Fernandez, C. Hill, H. Sancho-Gamier dosage estimations that are roughly threefold higher than the and M. Tubiana for helpful scientific discussions. MIRD estimation of 0.14 cGy/37 MBq (1 mCi) (3,4). Further Supported in part by a grant from the Association pour Ia more, patients were hypothyroid at the time of radioiodine admin Recherche sur le Cancer, from the Radioprotection Programme of istration and this condition can decrease iodine renal clearance and the European Communities, from the Fondation de France (Leg result in a more prolonged gonadal exposure. Women treated with Doris Levy), from COGEMA and from FRAMATOME, from EEC more than 3.7 GBq (100 mCi) of radioiodine generally had lung Biomed Program (BMH 1-CT92-008 I ) and from the National metastases and received a mean cumulative activity of 8.8 GBq Research Council (CNR, Rome, Italy) Target Project ACRO Grant (237 mCi) before conception. In these women, the dose delivered 93.02220 PF 39 and from Associazione Italiana per Ia Ricerca sut to the ovaries can be estimated to be 0.4 cGy/37 MBq, assuming Cancro (A.I.R.C.). lung uptake of 10% at 24 hr, leading to a mean total dose to the ovaries of about 1 Gy. Fifty-seven malformations were recorded among the 1384 REFERENCES I. Dunn iT. Choice of therapy in young adults with hyperthyroidism of Graves' disease. children born to unexposed mothers. Assuming a doubling dose M Ann Intern ed I984;lOO:891â€”893. of 1 Gy (39), a theoretical number of5.02 malformations would 2. Beierwaltes WH, Nishiyama RH, Thompson NW. Copp JE, Kubo A. Survival time and be expected for the 61 children born of mothers exposed to in â€œcureâ€•papillary and follicular thyroid carcinoma with distant metastases: statistics following University of Michigan therapy. J Nuci Med 1982:23:561â€”568. more than 3.7 GBq ( 100 mCi). Based on this theoretical value, 3. MIRD. MIRDprimerfor absorbeddosecakulations. Reston,VA: Societyof Nuclear the probability ofobserving among these 61 children two or less Medicine: 1988. G 4. Izembart M, ChavaudraJ, Aubert B, VallÃ©e . Retrospectiveevaluation of the dose malformations is 13% (33). In fact, only two malformations received by the ovary after radioactive iodine therapy for thyroid cancer. Eur J Nuci were observed. This excludes, with a probability of 87%, that a Med 1992:19:243â€”247. radiation dose of 1 Gy to the ovaries results in an increase in the 5. SchuIl Wi, Otake M, Ned JV. Genetic effects of the atomic bombs: a re-appraisal. Science 1981:213:1220â€”1227. risk of malformation by a factor of two or more. This may be 6. Otake M, SchulI WI, NeeI JV. Congenital malformations.stillbirths and early related to uncertainty regarding the doubling dose in humans mortality among the children of atomic bomb survivors: a re-analysis. Radial Res 1990:122:1â€”11. which may be much higher than 1 Gy in women (5,39), and to 7. Yoshimoto Y, Ned JV, SchuII Wi, et aI. Malignant tumors during the first two decades the low dose rate of 131J Induced abortions are unlikely to have of life in the offspring of atomic bomb survivors. Am J Hum Genet 1990:46:1041â€” masked an increased incidence of malformations, since the 1052. 8. Mulvihill ii, Myers MH, Connelly RR, Ct al. Cancer in offspring of long-term incidence of induced abortions was not related to the cumula survivors of childhood and adolescent cancer. Lancel I987;2:8I3â€” 817. tive activity of radioiodine administered before pregnancy. 9. Hawkins MM, Draper Gi. Smith RA. Cancer among 1348 offspring of survivors of The incidence of thyroid diseases was 1% in liveborn children, childhood cancer. mi i Cancer I989:43:975â€”978. 10. Hawkins MM. Is there evidence of a therapy related increase in germ cell mutation with no difference between exposed and unexposed groups. among childhood cancer survivors? J Nail Cancer Ins: 1991:83:1643â€”1650. A total of seven malignancies was observed among children, I I. Gardner Mi, Snee MP. Hall AJ, et al. Results of a case.control study of leukemia and five born to unexposed mothers and two to exposed mothers. lymphoma among young people near Sellafield nuclear plant in West Cumbria. Br Med J 1990:300:423â€”429. When compared to the number ofexpected cancers from French 12. Tubiana M, 5chlumberger M. Rougier P. et al. Long-term results and prognostic cancer registries, the relative risk was 2.1 (95% CI: O.8%â€” factors in patients with differentiated thyroid carcinoma. Cancer 1985;55:794â€”804. 13. Simpson Wi, Panzarella T. Carruthers i5, et al. Papillary and follicular thyroid cancer: 4.3%), which is not increased significantly. This is in agreement impact of treatment in 1578 patients. mi i Radiation Oncol Biol P/irs 1988:14: I063â€” with studies of offspring of the survivors of the atomic bombs 1075. in Japan (7) and of childhood cancer survivors who had 14. 5chlumberger M. De Vathaire F, Travagli JP. et al. Differentiated thyroid carcinoma in childhood: long term follow.up of 72 patients. J Clin Endocrinol Metab 1987:65: received abdominal irradiation (8,9). At variance with these 1088â€”1094. data, however, an association between paternal preconception 15. Hay ID. Papillary thyroid carcinoma. Endocrinol Metab Clinics of North America exposure to radiation and the risk of leukemia among offspring I990; I9:545â€”576. 16. Samaan NA, Schultz PN, Haynie TP. Ordonez NG. Pulmonary metastasis of has been reported in children of workers at the Seltafietd differentiated thyroid carcinoma: treatment results in 101 patients. J C/in Endocrinol nuclear plant (11). Metab 1985:60:376â€”380. I7. Schlumberger M, Tubiana M, De Vathaire F. et al. Long-term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma. J CONCLUSION C/in Endocrinol Metab 1986:63:960â€”967. With the exception of miscarriages, there is no evidence that 18. HayekA, ChapmanEM, CrawfordJD. Long-termresultsof treatmentof thyrotoxi cosis in children and adolescents with radioactive iodine. N Engi J Med 1970:283: exposure to radioiodine affects the outcome of subsequent 949â€”953. pregnancies and offspring, even in women receiving cumulative 19. Safa AM, Schumacher OP. Rodriguez-Antunez A. Long-term follow-up results in doses to the ovaries as high as 1 Gy. Although the number of children and adolescents treated with radioactive iodine for hyperthyroidism. N EngI JMed 1975;292:167â€”l71. children born of mothers exposed to radioiodine is relatively 20. Freitas JE, 5wanson DP, Gross MD, Sisson JC. Iodine-13 I: optimal therapy for small, the present data indicate that there is no reason for 8 hyperthyroidism in children and adolescents? J Nucl Med 1979:20:847â€” 50. 21. Winship 1, Rosvoll RV. Thyroid carcinoma in childhood. Final report on a 20-yr patients exposed to radioiodine to avoid pregnancy. The only P study. roc NailCancerCon! 1970:6:677â€”681. adverse effect observed in our series is an increased incidence 22. Einhorn I, Hulten M, Lindsten J, et al. Clinical and cytogenetic investigation in of miscarriages in women exposed to therapeutic radioiodine children of parents treated with radioiodine. Ada Radio! 1972:1 1:193â€”208. 23. Sarkar SD, Beierwaltes WH, Gill SP, Cowley Bi. Subsequent fertility and birth during the year which preceded conception. The question of â€˜I for histories of children and adolescents treated with â€˜@ thyroid cancer. J NucI Med whether and to what extent this should be attributed to radio 1976; I7:460â€”464. PREGNANCY AND RADIOIODINE Schlumberger â€¢ et al. 611 24. Edmonds Ci, Smith T. The long-term hazards of the treatment of thyroid cancer with 33. Breslow NE, Day NE. The design and analysis of cohort studies. IARC, Scientific radioiodine. Br J Radio! I986:59:45â€”51. Publication #2, Lyon, France. 1987. 25. Emnch D. Creutzig H. Benefits and risks ofradioactive iodine therapy in differentiated 34. Coleman MP, Hermon C, Douglas A. Person-years (PYRS). A fortran program for thyroid carcinoma. Prog Surg 1988:19:133â€”146. cohort study analysis. JARC internal Report 89, Lyon, France, 1989. 26. Casara D. Rubello D, Saladini G, et al. Pregnancy after high therapeutic doses of iodine-I 3 I in differentiated thyroid cancer: potential risks and recommendations. Eur 35. Muir C, Waterhouse J, Mack T. Powell I. Cancer incidence in five continents. IARC J Nuc/Med I993:20: I92â€” I94. Scientific Publication 88. Lyon, France, 1987. 27. Dottorini ME, Lomuscio G, Mazzucchelli L, ci al. Assessment of female fertility and 36. FranÃ§oisP, Beurtheret C, Dutreix A. Calculation of the dose delivered to organs carcinogenesis after iodine-I3 I therapy for differentiated thyroid carcinoma. J Nuc! outside the radiation beams. Medical Physics 1988;l 5:879â€” 883. Med I995;36:2Iâ€”27. 37. Kereiakes JG, Rosenstein M. Handbook of radiation doses in nuclear medicine and 28. Pacini F, Lippi F, Formica N, et al. Therapeutic doses of iodine-131 reveal undiagnosed metastases in thyroid cancer patients with detectable serum thyroglobulin diagnostic x-ray. Boca Raton, Florida; CRC Press: 1988. levels. J Nuc! Med 1987:28:1888-1891. 38. Bureau International du Travail. Classification internationale type des professions. 29. Leroy B, Lefort F. A propos du poids Ctde Ia taille des nouveau-nÃ©s Ia naissance. Rev a B GenÃ©ve: ureau International du Travail; 1985. Fr Gvnecoll97I;66:39lâ€”396. 39. United Nations Scientific Committee on the effects of atomic radiation: sources, 30. World Health Organization. The international classification ofdiseases. 9th Rev. vol. effects, and risks of ionizing radiation. Pub!. no. E88 IX 7 New-York; United Nations: I. Diseases tabular list. Geneva; World Health Organization: 1977. 1988. 3 1. Preston DL, Lubin ill, Pierce PA. Epicure user â€˜s guide (draft). Seattle; Hirosoft Inter Corp: 1990. LE,Gilbert S.Hessol A,McIntyre 40. Sever E N studyofcongenital iM.Acase-control e 32. Preston DL. In: Blot Wi, Hirayama T, Hod 113G. ds. Statistical Methods in Cancer malformations and occupational exposure to low-level ionizing radiation. Am J Epidemiology. Hiroshima, RERF: I985; I09 - I28. Epidemiol 127:226â€”242. 1988; ED@O@AL Genetic RiskAssessmentafter Iodine-131Exposure: An Opportunityand Obligationfor Nuclear Medicine A 11diagnostic and therapeutic modal tions the chance of untoward effects, risks, the potential hazards from 131!ther ities should be assessed carefully particularly those proposing more restric apy, which have the greatest impact on for the relative benefits and hazards so tive protocols, the available data on this the decision to utilize this modality, are patients and physicians can make rational issue are scant and inconclusive. the induction of second tumors (11,12) decisions. Atthough this basic principle Every nuclear physician should have a and genetic damage (13â€”23).These are would seem to be self-evident, the objec clear impression from clinicat practice considered to be stochastic effects with tive, practical evaluation of the pros and that 13II therapy is safe and that the level no threshold; virtually every patient cons of 1311 therapy is a particularly of risk is smaller than that of other treated with any dose of I3II is exposed complex task. therapeutic modalities routinely used in to some potential risk. Chromosomal ab The diagnostic and therapeutic use of oncology (e.g., external beam radiother normalities and genetic mutations which 1311 for the evaluation of thyroid rem apy and chemotherapy), but the time has express themselves in the offspring of nants and regional and distant metastases come to support this impression with exposed subjects are only relevant to of differentiated thyroid carcinoma indisputable data. While the risks are fertile individuals of reproductive age. (DTC), the ablation of remnants and the obviously small, fear of the unknown is Nuclear physicians dealing with radio I3 1I therapy of avid metastases have been the worst enemy of the medical use of nuclide therapy are asked almost daily by routine for decades. It has been half a radionuclides. The accurate and objec patients and referring physicians to de @ century since II was introduced into tive evaluation of the risk is thus an fine the extent of the risk. Thus, the rare medical practice, and a large body of important primary task of the nuclear contributions to the literature on this information has been gathered on the medicine community. subject, such as that from Schlumberger diagnostic and therapeutical effective et al. in this issue ofthe Journal (24), are ness of this modality (1â€”4). Neverthe COMPUCATIONS FROM IODINE-131 especially valuable and useful in every less, definitive results have yet to be ThERAPY day clinical practice. acquired, and the indications for the di The most common acute complica The paucity of available data in the agnostic and therapeutic use of I31I are tions of 131!therapy, radiation thyroiditis, literature on this topic stems from a still the subject ofdispute (5,6). Much of sialadenitis, gastrointestinal discomfort and number of factors. Remarkable method the difficulty arises from the low preva nausea, xerostomia and altered taste sen ological difficulties arise when assessing lence of DTC and the unusually long, sation are usually mild and self-limiting effects that are both infrequent and which natural history of the disease which ne (7,8); in fact, specific treatment is only have long latent intervals before becom cessitates the assembly of large series occasionally required. In the case of ing manifest (years for carcinogenesis which are meticulously followed for de commonly used doses of 1311 impair and at least a generation for diseases cades. While the exact utility of diagnos ment of gonadal function appears to be a formed from genetic mutations). Tumors tic and therapeutic I3II remains contro temporary reversible effect (9,10). and mutations induced by exposure to versial, the evaluation of the hazards of Edema and hemorrhage into the tumor ionizing radiation for medical purposes these applications remains even more may rarely cause serious problems when are generally indistinguishable from controversial and difficult to define. De metastases are located in the brain or those arising from other causes (e.g., spite the fact that virtually every paper near the airways. Among the late effects, chemicals, viruses and background radi @ II dealing with â€˜ treatment of DTC men permanent myetosuppression and pulmo ation). Therefore, determining the cause nary radiation fibrosis are dose depen of carcinogenesis and of genetic muta @ Received Aug. 23, 1995; accepted Sept. 2, 1995. dent, and thus, only the minority of tions from Ij exposure is impossible in For correspondenceor reprints contact: Massimo E. Dottom, MD, U.O.Medtcina Nucleare, sped@e@ patients treated with very high cumula O c individual cases (even if these are Circolo. PiazzaleSolaro31-21052Busto Arsizio, Italy. tive doses are at risk. In contrast to these grouped together), but depends on the 612 OFNUCLEAR THEJOURNAL â€˜ 37 â€¢ 4 . April 1996 Vol. MEDICINE No.
Pages to are hidden for
"Exposure to Radioactive Iodine- 131 for Scintigraphy or Therapy "Please download to view full document