Factors Associated With Radioactive Iodine Therapy–Acquired Nasolacrimal Duct Obstruction

ObjectiveTo identify factors associated with radioactive iodine (RAI)-acquired nasolacrimal duct obstruction (NLDO).MethodsRetrospective chart review and telephone surveys of patients who received RAI therapy for thyroid carcinoma at an academic institution were conducted. Telephone surveys were used to screen for post-RAI NLDO diagnoses. Databases were reviewed for documented NLDO, demographics, RAI dose, total number of RAI treatments, and sialadenitis. Routine post-RAI whole-body scintigraphy (WBS) images were analyzed for the presence or absence of ¹³¹I sodium iodide (I-131) in the nasolacrimal duct. Intranasal I-131 activity was graded as none, low, moderate, and high; those with moderate or high activity were considered to have “increased” activity. Logistic and ordinal logistic regression models were used to evaluate the associations with NLDO while adjusting for I-131 dose.ResultsOf the 209 patients who completed the survey, 15 (7%) had NLDO diagnoses. Increased intranasal I-131 activity on WBS, presence of nasolacrimal I-131 WBS activity, presence of documented post-RAI sialadenitis, and history of >1 RAI treatment were associated with the development of NLDO from univariate analyses (P ≤ .013). After adjusting for the administered dose of I-131, the presence of sialadenitis and nasolacrimal I-131 activity on WBS were the remaining 2 factors significantly associated with NLDO development (P < .001 and P = .01, respectively).ConclusionsThe presence of sialadenitis and nasolacrimal I-131 activity on WBS are I-131 dose-independent correlative factors for RAI-associated NLDO. Patients with these characteristics should be counseled on their increased risk of NLDO after RAI therapy for thyroid carcinoma.     

Iodine-131 dose dependent gene expression in thyroid cancers and corresponding normal tissues following the chernobyl accident

The strong and consistent relationship between irradiation at a young age and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis in humans. We thus evaluated differential gene expression in thyroid tissue in relation to iodine-131 (I-131) doses received from the Chernobyl accident. Sixty three of 104 papillary thyroid cancers diagnosed between 1998 and 2008 in the Ukrainian-American cohort with individual I-131 thyroid dose estimates had paired RNA specimens from fresh frozen tumor (T) and normal (N) tissue provided by the Chernobyl Tissue Bank and satisfied quality control criteria. We first hybridized 32 randomly allocated RNA specimen pairs (T/N) on 64 whole genome microarrays (Agilent, 4×44 K). Associations of differential gene expression (log(2)(T/N)) with dose were assessed using Kruskall-Wallis and trend tests in linear mixed regression models. While none of the genes withstood correction for the false discovery rate, we selected 75 genes with a priori evidence or P kruskall/P trend <0.0005 for validation by qRT-PCR on the remaining 31 RNA specimen pairs (T/N). The qRT-PCR data were analyzed using linear mixed regression models that included radiation dose as a categorical or ordinal variable. Eleven of 75 qRT-PCR assayed genes (ACVR2A, AJAP1, CA12, CDK12, FAM38A, GALNT7, LMO3, MTA1, SLC19A1, SLC43A3, ZNF493) were confirmed to have a statistically significant differential dose-expression relationship. Our study is among the first to provide direct human data on long term differential gene expression in relation to individual I-131 doses and to identify a set of genes potentially important in radiation carcinogenesis.     

Enhancement of Natural Killer Cell Cytotoxicity by Sodium/Iodide Symporter Gene-Mediated Radioiodine Pretreatment in Breast Cancer Cells

A phase II study of NK cell therapy in treatment of patients with recurrent breast cancer has recently been reported. However, because of the complexities of tumor microenvironments, effective therapeutic effects have not been achieved in NK cell therapy. Radioiodine (I-131) therapy inhibits cancer growth by inducing the apoptosis and necrosis of cancer cells. Furthermore, it can modify cancer cell phenotypes and enhance the effect of immunotherapy against cancer cells. The present study showed that I-131 therapy can modulate microenvironment of breast cancer and improve the therapeutic effect by enhancing NK cell cytotoxicity to the tumor cells. The susceptibility of breast cancer cells to NK cell was increased by precedent I-131 treatment in vitro. Tumor burden in mice treated with I-131 plus NK cell was significantly lower than that in mice treated with NK cell or I-131 alone. The up-regulation of Fas, DR5 and MIC A/B on irradiated tumor cells could be the explanation for the enhancement of NK cell cytotoxicity to tumor cells. It can be applied to breast cancer patients with iodine avid metastatic lesions that are non-responsive to conventional treatments.     

Evaluation of equivalent body burden in the thyroid for the people of Poland on results of 131I absorption after the disaster in Czernobyl. Determination of thyroid blockade with potassium iodide]

An assessment of effectiveness of the administering of single dose of stable iodine in Poland on the reduction of 131I doses in thyroid has been performed. 5-compartment model of metabolism of iodine developed by Johnson has been used to evaluate predicted levels of stable iodine and 131I content in thyroid and commitment dose equivalent H50 for different doses of stable iodine and various age and sex group population. The measured values of 131I concentration in air and in milk and standard values for milk and food consumption and inhalation rate as well as metabolic parameters were used. Theoretical calculations showed that administering of stable iodine on 1986-04-28, 1986-04-29, 1986-04-30 and 1986-05-01 could have reduced committed dose equivalent H50 form ingestion with inhalation pathway by about 44%, 40%, 26%, 12% respectively. On the basis of measured 131I activity in the thyroid for inhabitants from different districts in Poland (1400 measurement) committed dose equivalents were determined and analysis of radiation hazard from 131I were performed. In the most contaminated regions of Poland average H50 doses for children 1-5 and 5-10 years old are close to 50 mSv (permissible level for population) and maximal doses exceed this limit four times. These maximal doses occurred for about from 5% inhabitants from these area. In the moderate and low contaminated regions of Poland the average doses are fivefold and tenfold less respectively.     

Therapeutic Implications of Diffuse Hepatic Uptake Following I-131 Therapy for Differentiated Thyroid Cancer

ObjectiveTo determine if diffuse hepatic uptake (DHU) of radioactive iodine (I-131) following radioactive iodine treatment has prognostic implications in otherwise scan-negative patients.MethodsThis is a retrospective review of patients treated for differentiated thyroid cancer (DTC) at Beth Israel Deaconess Medical Center between January 1990 and June 2006. This group included patients receiving therapy to ablate presumed remnant tissue, as well as treatment for persistent disease as measured by thyroglobulin or imaging. All patients included in the study had no remnant uptake and otherwise negative posttherapy scans. A total of 57 patients with 63 scans met these criteria. The scans were then scored for DHU on a scale of 0 to 5, with 0 being no uptake and 5 being intense uptake relative to background.ResultsSixteen of 63 treatments were remnant ablations. Ten of 57 patients had positive thyroglobulin antibodies. Average DHU was similar in the ablation and therapeutic groups (1.9 vs. 2.3, P = .3). There was no correlation with either I-131 dose or the presence of thyroglobulin antibodies. There was a difference for DHU in the rate of disease-free survival, (undetectable thyroglobulin and no clinical or radiographic evidence of metastasis); 50% of patients with hepatic uptake scores of 0-2 were disease-free compared to 15% with scores of 3-5 (P<.01). The average length of follow-up for disease-free patients was 4.6 years.ConclusionIn patients with DHU with otherwise negative whole-body scans following I-131 treatment, more intense hepatic uptake is associated with lower likelihood of complete response to I-131 treatment. (Endocr Pract. 2013;19:263-267)     

Thyroid dose reconstruction for the population of Belarus after the Chernobyl accident

An ¹³¹I environmental transfer model – adapted for Belorussian conditions – was applied to estimate thyroid doses for different population groups. For this purpose the available data were analysed and the important radioecological parameters assessed, i.e. (a) the elimination rate of ¹³¹I from grass due to weathering and growth dilution, (b) the initial interception of ¹³¹I by vegetation, (c) the transfer coefficient for ¹³¹I from grass to cow's milk, (d) the yield of pasture grass and (e) the milk consumption rate. Additionally, the influence of applied countermeasures has been taken into account, such as the interruption of locally produced milk consumption, and the appropriate correction factors have been estimated. As a result, the average age-dependent thyroid doses were assessed for the Belorussian population. The highest average doses in children (> 1 Gy) have been estimated for the Bragin, Khoiniki, Narovlia and Vetka raions of the Gomel oblast. The thyroid exposure tends to decrease from the southeastern (closest to the Chernobyl nuclear power plant areas) to the northwestern part of the republic. When comparing the assessed thyroid doses with dose estimates derived from direct ¹³¹I activity measurements in thyroids (for the locations with more than 15 direct measurements), the results agree fairly well. The model calculation may perhaps overestimate thyroid doses of the population residing in the settlements of the central and northern parts of Belarus, distant from the areas with direct measurements of ¹³¹I activities in soil, grass and milk. These thyroid dose estimates may serve as a basis for further epidemiological studies and risk analyses.     

Molecular nuclear therapies for thyroid carcinoma

Thyroid cancer, divided in the subvarieties of papillary and follicular carcinoma, together also called differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC), is the most common endocrine malignancy. Over the course of the last seven decades multiple molecular nuclear therapies have been tried to treat the various varieties of thyroid cancer. The sodium iodine symporter (NIS) substrate I-131 is a well known and extremely successful agent to treat DTC, but is not successful in treating other thyroid cancer varieties and some de-differentiated DTC tumors. An alternative to I-131 are radioactively labeled somatostatin analogues, which have predominantly been used to target MTC, but may also be effective in some DTC cases. In experimental preclinical studies the re-induction of NIS expression or transfection with recombinant NIS shows some promise for the treatment of ATC and dedifferentiated DTC. Furthermore, several other potential radioactive NIS substrates are developed. In this review, we will extensively discuss the aforementioned established therapeutic modalities and promising new concepts in molecular nuclear therapy of thyroid carcinoma.     

Radioimmunotherapy for breast cancer: treatment of a patient with I-131 L6 chimeric monoclonal antibody.

We report the first treatment of metastatic breast cancer by systemic radioimmunotherapy. The serial therapy doses were chosen based on quantitative imaging data in a treatment planning approach. A terminally ill patient with aggressive, locally advanced breast cancer who had failed radiation treatment and chemotherapy was injected intravenously with radiolabeled I-131 chimeric L6, a human-mouse chimeric lgG1 monoclonal antibody to adenocarcinoma. Initially, an imaging 10 mCi dose of I-131 chimeric L6 (dose 1) deposited 8.8% of the injected dose in her chest wall tumor at 48 hours. Ten days later the patient was given a 150 mCi I-131 chimeric L6 dose (dose 2) followed three weeks later by a 100 mCi dose (dose 3). Tumor uptake and retention were comparable for doses 1 and 2, and decreased for dose 3. Following dose 3 the patient developed a manageable thrombocytopenia and transient Grade IV granulocytopenia. The tumor was observed to decrease in size with peak tumor regression occurring two weeks after dose 3. This partial response (PR) was achieved by radioimmunotherapy at a time when conventional therapy had been unable to impact the growth of the patient's massive and aggressive tumor.     

MnTnBuOE-2-PyP treatment protects from radioactive iodine (I-131) treatment-related side effects in thyroid cancer

Treatment of differentiated thyroid cancer often involves administration of radioactive iodine (I-131) for remnant ablation or adjuvant therapy. However, there is morbidity associated with I-131 therapy, which can result in both acute and chronic complications. Currently, there are no approved radioprotectors that can be used in conjunction with I-131 to reduce complications in thyroid cancer therapy. It is well known that the damaging effects of ionizing radiation are mediated, in part, by the formation of reactive oxygen species (ROS). A potent scavenger of ROS, Mn(III)meso-tetrakis(N–n-butoxyethylpyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP), has radioprotective and anti-tumor effects in various cancer models including head and neck, prostate, and brain tumors exposed to external beam radiation therapy. Female C57BL/6 mice were administered I-131 orally at doses of 0.0085–0.01 mCi/g (3.145 × 105 to 3.7 × 105 Bq) of body weight with or without MnTnBuOE-2-PyP. We measured acute external inflammation, blood cell counts, and collected thyroid tissue and salivary glands for histological examination. We found oral administration of I-131 caused an acute decrease in platelets and white blood cells, caused facial swelling, and loss of thyroid and salivary tissues. However, when MnTnBuOE-2-PyP was given during and after I-131 administration, blood cell counts remained in the normal range, less facial inflammation was observed, and the salivary glands were protected from radiation-induced killing. These data indicate that MnTnBuOE-2-PyP may be a potent radioprotector of salivary glands in thyroid cancer patients receiving I-131 therapy.     

Thyroid dose assessment for the Chernigov region (Ukraine): Estimation based on131I thyroid measurements and extrapolation of the results to districts without monitoring

Based on the results of¹³¹I thyroid activity measurements in three districts of the Chernigov region (Ukraine), individual doses were calculated and an approach of the age dependence of the average thyroid exposure was derived. Using the relationships between the thyroid doses and the¹³⁷Cs deposition as well as the location relative to the Chernobyl Nuclear Power Plant (NPP), age-dependent average thyroid doses were extrapolated also for those settlements of this region where no monitoring measurements have been carried out. The highest doses were found in the west of the region with the lowest distance to the Chernobyl NPP. In this part, the highest mean of the thyroid dose in a settlement was 3.3 Gy for infants and 0.5 Gy for adults. The collective thyroid dose was 31000 and 27 000 person-Gy for children and adults, respectively. Based on this assessment, 140 and 21 excess thyroid cancer cases are predicted for children and adults, respectively. In the years 1989 to 1991, in the whole contaminated territory of the Ukraine 0.4–1.2 cases per 100000 children were observed. Although the absolute numbers are very small, this indicates the possibility of an increase in thyroid cancer morbidity among children. The same trend also seems to be indicated in the Chernigov region. A careful epidemiological study in the future is necessary to enable a final evaluation of radioinduced cancers in this region.     

A preliminary assessment of the consequences for inhabitants of the UK of the Chernobyl accident

The accident with the nuclear power reactor at Chernobyl in the USSR resulted in the release of substantial quantities of radioactive material and subsequent increases in radioactivity in the environment in many countries. In this paper the situation in the UK is considered and, from the preliminary monitoring measurements, the major routes of exposure of the population are identified and quantified. For the most part exposures in the UK are within variations in levels of natural background radiation to be found in Europe. An exception is the dose likely to have been received by the thyroids of young people in the north of the UK. From reported measurements of I-131 in milk it is predicted that thyroid doses up to 10-20 times the annual doses received from 'normal' natural background radiation might have affected young children drinking fresh cows' milk. The ways in which this component of exposure could have been reduced and the criteria that govern decisions as to whether or not to implement counter-measures are discussed. The importance of I-131 in milk as a route of exposure of the population to radioactivity is a feature that the Chernobyl accident has in common with the Windscale accident in the UK in 1957, and underlines the importance of milk-producing regions in relation to reactor-sitting policy.     

<Superscript>131</Superscript>I age-dependent inhalation dose in Southern Poland from Fukushima accident

A general method for calculating doses absorbed from isotopes released in nuclear accidents is presented. As an example, this method was used to calculate doses for inhabitants of Southern Poland due to inhalation of ¹³¹I released due to the Fukushima nuclear plant accident. ¹³¹I activity measurements in the air of that region provided the basis for the study. The proposed model is based on a complex biokinetic model for iodine merging the Leggett model developed in 2010 with the human respiratory tract and gastrointestinal tract models recommended by the International Commission on Radiological Protection (ICRP). This model is described here, and it is demonstrated that resulting dose estimates are consistent with those obtained using the ICRP methodology. Using the developed model, total doses were calculated for six age groups of both genders, for gaseous and aerosol fractions alike. The committed effective dose, H ₅₀, for an adult man reached 16 nSv, which is lower than 0.001% of the background dose. The dose for the thyroid of an adult reached 0.33 μSv, which corresponds to circa 0.0007% of the dose to the population of Southern Poland after the Chernobyl nuclear plant accident.     

Thyroid dose and thyroid cancer incidence after the Chernobyl accident: assessments for the Zhytomyr region (Ukraine)

In the Zhytomyr region, about 52 000 measurements of the ¹³¹I activity in thyroids were performed. On the basis of these measurements, individual doses have been assessed for the people monitored and age-dependent average doses have been estimated for those settlements with more than 11 direct measurements. In order to estimate the pattern of thyroid exposure in the Zhytomyr region, these doses have been interpolated or extrapolated to population groups who were not monitored during May–June 1986. For this purpose, a model has been developed based on a correlation between thyroid dose estimates with the ¹³⁷Cs deposition and the co-ordinates of the settlements relative to Chernobyl. Collective doses of people who were born in the years 1968 to 1986 were calculated. The radiation-induced thyroid cancer incidence in the period 1991 to 1995 was assessed by subtracting the spontaneous incidence from the observed incidence. The result is considerably lower than that observed in longer periods after external exposures. Possible reasons for this difference are discussed. Received: 17 January 1997 / Accepted in revised form: 2 October 1997     

Increased Risk of Radioiodine Treatment Failure Associated with Graves Disease Refractory to Methimazole

Objective: Iodine 131 (I-131) radioactive iodine (RAI) therapy has been the preferred treatment for Graves disease in the United States; however, trends show a shift toward antithyroid drug (ATD) therapy as first-line therapy. Consequently, this would favor RAI as second-line therapy, presumably for ATD refractory disease. Outcomes of RAI treatment after first-line ATD therapy are unclear. The purpose of this study was to investigate treatment failure rates and potential risk factors for treatment failure, including ATD use prior to RAI treatment.Methods: A retrospective case control study of Graves disease patients (n = 200) after I-131 RAI therapy was conducted. Treatment failure was defined as recurrence or persistence of hyperthyroidism in the follow-up time after therapy (mean 2.3 years). Multivariable regression models were used to evaluate potential risk factors associated with treatment failure.Results: RAI treatment failure rate was 16.5%. A majority of patients (70.5%) used ATD prior to RAI therapy, predominantly methimazole (MMI) (91.9%), and approximately two-thirds of patients used MMI for >3 months prior to RAI therapy. Use of ATD prior to RAI therapy (P = .003) and higher 6-hour I-123 thyroid uptake prior to I-131 RAI therapy (P<.001) were associated with treatment failure. MMI use >3 months was also associated with treatment failure (P = .002).Conclusion: More patients may be presenting for RAI therapy after failing first-line ATD therapy. MMI use >3 months was associated with RAI treatment failure. Further studies are needed to investigate the association between long-term first-line ATD use and RAI treatment failure.     

^131I标记Tyr-GX1在荷瘤裸鼠体内分布和显像研究

目的：设计、合成酪氨酸（Tyr）修饰的肿瘤血管靶向肽GX1,研究^131I标记短肽Tyr-GX1在荷人胃癌裸鼠体内的生物学分布与显像,探讨^131I-Tyr-GX1短肽作为肿瘤血管靶向诊治药物的可能性。方法：利用Iodogen碘标法对Tyr-GX1进行131I标记,检测其标记率和体内外稳定性;建立荷人胃癌裸鼠动物模型,尾静脉注射标记肽,分别进行体内生物学分布实验和肿瘤显像实验,结果用PASW Statistics18.0统计软件进行分析。结果：1）.纸层析法结果计算表明,^131I-Tyr-GX1肽的标记率和放化纯均达90%以上;24 h稳定性测试表明,^131I-Tyr-GX1在室温下存放以及与人血清、鼠血清、PBS等溶液混合,其标记率仍然都维持在90%左右,说明其具有良好的体内外稳定性;2）.荷瘤裸鼠体内生物学分布研究显示：标记肽在荷瘤裸鼠双肾放射性计数测量最高;其次是肝脏、肿瘤等组织;脑、骨、肌肉组织放射性计数含量较低,给药24 h时,肿瘤/肌肉（T/M）、肿瘤/血液（T/Bl）、肿瘤/脑组织（T/Br）的放射性比值分别是5.78、4.06和23.01;3）.体内SPECT显像结果显示：尾静脉注射^131I-Tyr-GX1肽后4 h肿瘤部位已开始显影,并随时间的延长,显像逐渐清楚,至18 h时,肿瘤显像最清晰。结论：应用Iodogen碘标法成功标记Tyr-GX1短肽;尾静脉注射^131I-Tyr-GX1后,肿瘤部位可以出现放射性浓聚,表明^131I-Tyr-GX1短肽可以靶向结合于肿瘤部位,有望成为新一种胃肠道肿瘤诊断与治疗的药物。     

Obituaries

The outcome in 110 patients first treated with radioiodine (mean dose 6.56 mCi) for hyperthyroid Graves'' disease in 1980 was reviewed. In 23% of the patients the disease had not been controlled by the initial dose after 3 months, and 17% were given one or two more doses. Within 2 years 65% of the patients required replacement thyroxine therapy. Although about half of the patients were biochemically hypothyroid 3 months after the last dose of iodine 131, this condition was transient in a third of them; five of these patients even became hyperthyroid again. Patients with transient, as opposed to permanent, hypothyroidism at 3 months tended to be clinically euthyroid but to have residual palpable thyroid tissue and only a modest reduction in the serum thyroxine level. It is therefore recommended that patients not overtly hypothyroid 3 months after treatment with 131I be observed still longer before thyroxine replacement therapy is instituted.     

TDP-43 toxicity in yeast

Metaiodobenzylguanidine (MIBG) is a tracer that selectively targets neuroendocrine cells. On this basis, radiolabeled iodinated-MIBG (I-131-MIBG) has been introduced as a molecular nuclear therapy in the management of neuroendocrine tumors, including neuroblastoma, pheochromocytoma, paraganglioma, neuroendocrine carcinomas, and other rare neuroendocrine tumors. Extensive work has been addressed to develop I-131-MIBG therapy: doses, therapeutic schemes, and efficiency. In this paper, we present an overview on I-131-MIBG therapy, with main focus on different aspects how to perform this treatment.     

Measurement of <Superscript>131</Superscript>I activity in air indoor Polish nuclear medical hospital as a tool for an internal dose assessment

This paper presents results of ¹³¹I air activity measurements performed within nuclear medical hospitals as a tool for internal dose assessment. The study was conducted at a place of preparation and administration of ¹³¹I (“hot room”) and at a nurse station. ¹³¹I activity measurements were performed for 5 and 4 consecutive working days, at the “hot room” and nurse station, respectively. Iodine from the air was collected by a mobile HVS-30 aerosol sampler combined with a gas sampler. Both the gaseous and aerosol fractions were measurement. The activities in the gaseous fraction ranged from (28?±?1 Bq m^?3) to (492?±?4) Bq m^?3. At both sampling sites, the activity of the gaseous iodine fraction trapped on activated charcoal was significantly higher than that of the aerosol fraction captured on Petrianov filter cloth. Based on these results, an attempt has been made to estimate annual inhalation effective doses, which were found to range from 0.47 mSv (nurse female) to 1.3 mSv (technician male). The highest annual inhalation equivalent doses have been found for thyroid as 32, 27, 13, and 11 mSv, respectively, for technician male, technical female, nurse male, and nurse female. The method presented here allows to fill the gaps in internal doses measurements. Moreover, because method has been successful used for many years in radioactive contamination monitoring of air in cases of serious nuclear accidents, it should also be used in nuclear medicine.     

The effects of cobalt and iodine supplementation of the pregnant ewe diet on immunoglobulin G, vitamin E, T3 and T4 levels in the progeny

Sixty twin-bearing ewes were allocated to one of four dietary treatments investigating the effects of supplementary iodine or cobalt during late pregnancy on lamb serum immunoglobulin G (IgG), triiodothyronine (T3), thyroxine (T4) and vitamin E concentrations, and lamb IgG absorption efficiency. Ewes were offered grass silage ad libitum supplemented with 800 g per ewe per day of a 190 g/kg crude protein (CP) concentrate from day 126 of gestation until parturition plus one of the following supplements (n = 15 per treatment); no supplement (C); 26.6 mg iodine per day for final 3 weeks pre partum (I-3); 26.6 mg iodine/day for final week pre partum (I-1); 20 mg cobalt/day for final 3 weeks pre partum (Co-3). Lambs were blood sampled at 24 and 72 h post partum for serum IgG and vitamin E concentrations. Ten lambs from C and I-3 were blood sampled at 1 h post partum for serum IgG, vitamin E, T3 and T4 concentrations. There were no differences in serum IgG, vitamin E or T4 values (P > 0.05) at 1 h post partum between lambs born to the C and I-3 ewes. T3 levels were lower in I-3 compared with C progeny (P < 0.05). Supplemental iodine reduced colostral IgG absorption efficiency (P < 0.001) and lamb serum IgG concentrations at 24 and 72 h post partum (P < 0.001). Serum vitamin E concentration in I-3 and I-1 lambs was lower than in Co-3 lambs at 24 h post partum, while at 72 h post partum I-3, I-1 and Co-3 lambs had significantly lower concentrations than C lambs (P < 0.001). Supplementing the ewe's diet with 26.6 mg/day of iodine for the final week of pregnancy reduced lamb serum IgG concentration at 24 and 72 h post partum. The lower total and free T3 values in the progeny of I-3-treated ewes suggest interference in the synthesis and metabolism of thyroid hormones when ewes receive excessive dietary iodine for 3 weeks immediately pre partum. Based on these findings, the indications are that the toxicity level for iodine in the diet of the pregnant ewe should be lowered to 20 mg per ewe per day, equivalent to 40% of its current level. The finding that high-level cobalt supplementation during the final 3 weeks of pregnancy will have a negative effect on serum vitamin E concentration at 72 h post partum is a new and significant finding and previously has not been reported in the literature.     

Les métastases pulmonaires micronodulaires de type miliaire dans le cancer thyroïdien bien différencié (médullaires exclus) à propos de dix cas

Thyroid cancer is relatively a rare cancer; about 1% from all cancers; between 10 and 15% of patients with differentiated thyroid cancer develop micro or macronodular pulmonary metastases. In this study we examined the characteristics and evolution after treatment of 10 patients with micronodular or miliary metastases of well-differentiated thyroid carcinoma. Total body scintigraphy with 131 iodine, chest X-ray or CT scan, and thyroglobulin assay were performed for all patients. The treatment was iodine 131 (3, 7 GBq), therapeutic 131 iodine scan was done for all patients seven days after the 131 administration. The effect of 131 iodine treatment was evaluated by means of changes in the number and size of lung metastases on the total body scintigraphy with 131 iodine and by serum thyroglobulin levels six months after 131 iodine ablation, they all received L-thyroxin (2,4 μg/kg/j). The minimum duration of follow-up was 12 months. There were six females and four males within a range of 13–70 years old. Eight had papillary and two follicular thyroid cancer. These 10 patients benefited 131 iodine therapy. The effect of 131 iodine treatment and the prognostic values of the following variables were examined: age at the time of 131 iodine, treatment and histological findings. The miliary was rarely diagnosed on the initial investigation, only in two cases by 131 iodine scan after surgery, two cases by chest X-ray, and two cases by CT scan, the initial thyroglobulin levels was very high in seven cases, between 10 and 40 ng/ml in one case and less than 10 ng/ml in two cases. These results indicate that age, 131 iodine uptake, histological findings and the presence of other metastases are important factors in predicting the effects of 131 treatment for pulmonary metastases of well-differentiated thyroid carcinoma. Among all the variables studied, the best prognosis for survival was demonstrated by increased 131 uptake in pulmonary metastases and by early diagnosis during post surgery 131 iodine scanning of radiologicaly inapparent metastases.