RESUMO
Several exposure limits for perchlorate have been developed based on an early key event, inhibition of radioactive iodide uptake (RAIU) by the thyroid. These assessments have used a variety of definitions of the point of departure. The current assessment revisited the modeling for inhibition of RAIU, using state of the science methods. Bayesian hierarchical modeling was used to account for the repeated measures on the same individuals in the key dataset, and the underlying Beta distribution used for the modeling correctly reflected the bounding of RAIU between 0 and 1. We defined the BMR as a point value of 8% RAIU (rather than a change in RAIU), based on descriptions in the medical literature that RAIU below this value is considered abnormal. Because a definition of the BMR based on the mean response would correspond to about 50% of the population with a response below the BMR at the benchmark dose, we used a hybrid definition of the BMR. That is, the BMD was defined as the dose at which it was estimated that there would be a 10% extra risk in the population of having RAIU of 8% or lower. The resulting point of departure based on the BMDL was 0.03 mg/kg-day.
Assuntos
Cloratos/toxicidade , Modelos Biológicos , Percloratos/toxicidade , Cloratos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Radioisótopos do Iodo/metabolismo , Masculino , Pessoa de Meia-Idade , Percloratos/administração & dosagemRESUMO
Perchlorate, as an oxidizer, has many applications such as explosives and pyrotechnics, especially in rocket propellants and missile motors. Because it was found in water including wells and drinking water in the US, its effect on human health was being noted. However, the reproductive toxic effect on perchlorate is still unclear. In present study, the effects of repeated exposure to perchlorate on reproductive toxicity were evaluated in Wistar rats. The rats were treated orally with perchlorate at doses of 0.05, 1.00 or 10.00â¯mg/kg body weight (b.w.) daily for 8 weeks. The levels of T3 and T4 hormones in the rat serum were detected by radioimmunoassay kit. The indexes of reproduction, percentage of organ in body weight (%) and frequency of abnormal sperm cells were also analyzed in this study. DNA damage in testicular cells was evaluated by Comet assay. The levels of MDA, GSH and SOD were examined in testicle tissues of rats by ELISA. The expression of c-fos and fas protein was examined in testicle tissues by immunohistochemistry. The results showed that perchlorate did not affect the body weight of rats. Perchlorate also significantly decreased indexes of live birth and weaning in the groups of 1.00 and 10.00â¯mg/kg, and viability index only in the 10.00â¯mg/kg group (Pâ¯<â¯0.05). Perchlorate also significantly decreased the serum level of T3 in male rats of 1.00 and 10.00â¯mg/kg groups, increased the rate of sperm abnormality (10.00â¯mg/kg), potentially caused DNA damage in testicular cells and altered the status of oxidative stress in male rats. In addition, because of the increase in the expression of fas and c-fos protein in testicle tissues, perchlorate could induce apoptosis in spermatogenesis. Thus, these findings indicate that perchlorate could cause DNA damage in testicular tissues and reduce testicular spermatogenic ability, resulting in reproductive toxicity.
Assuntos
Percloratos/toxicidade , Compostos de Amônio Quaternário/toxicidade , Reprodução/efeitos dos fármacos , Animais , Ensaio Cometa , Dano ao DNA , Feminino , Masculino , Estresse Oxidativo/efeitos dos fármacos , Percloratos/administração & dosagem , Proteínas Proto-Oncogênicas c-fos/metabolismo , Compostos de Amônio Quaternário/administração & dosagem , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Tiroxina/sangue , Tri-Iodotironina/sangue , Receptor fas/metabolismoRESUMO
Imaging of cardiac sympathetic innervation is only possible by nuclear cardiology techniques and its assessment is key in the evaluation of and decision-making for patients with cardiac sympathetic impairment. This review includes the basis of cardiac sympathetic scintigraphy with 123I-meta-iodobenzylguanidine (123I-MIBG), recommended protocols, patient preparation, image acquisition and quantification, reproducibility, dosimetry, etc., and also the clinical indications for cardiac patients, mainly with regard to heart failure, arrhythmia, coronary artery disease, cardiotoxicity, including its contribution to establishing the indication for and monitoring the response to implantable cardiac devices, pharmacological treatment, heart transplantation and other.
Assuntos
3-Iodobenzilguanidina , Sistema de Condução Cardíaco/diagnóstico por imagem , Cardiopatias/diagnóstico por imagem , Coração/inervação , Radioisótopos do Iodo , Compostos Radiofarmacêuticos , Sistema Nervoso Simpático/diagnóstico por imagem , 3-Iodobenzilguanidina/administração & dosagem , 3-Iodobenzilguanidina/farmacocinética , Dispositivos de Terapia de Ressincronização Cardíaca , Pré-Escolar , Tomada de Decisão Clínica , Desfibriladores Implantáveis , Coração/diagnóstico por imagem , Sistema de Condução Cardíaco/fisiopatologia , Cardiopatias/induzido quimicamente , Cardiopatias/fisiopatologia , Transplante de Coração , Humanos , Processamento de Imagem Assistida por Computador , Infusões Intravenosas , Radioisótopos do Iodo/administração & dosagem , Radioisótopos do Iodo/farmacocinética , Norepinefrina/fisiologia , Percloratos/administração & dosagem , Compostos de Potássio/administração & dosagem , Prognóstico , Radiometria , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Receptores Adrenérgicos/fisiologia , Reprodutibilidade dos Testes , Sistema Nervoso Simpático/fisiopatologia , Glândula Tireoide/efeitos dos fármacos , Resultado do TratamentoRESUMO
Perchlorate is frequently found as contaminant in a variety of food. Based on analytical data of perchlorate occurrence in food products from the Austrian market, this study calculated dietary perchlorate exposure of the Austrian population for the three age classes of adults, children and infants. Furthermore, a detailed risk assessment was conducted based on the tolerable daily intake (TDI) of 0.3 µg/kg body weight/day, established by the European Food Safety Authority in 2014. Calculations of a scenario of average food consumption did not indicate elevated health risks by dietary perchlorate uptake. Exposure estimates reached only 12%, 26% and 24% of the TDI for adults, children and infants, respectively. However, in a scenario of high consumption, the TDI was exceeded by all age classes with 132%, 161% and 156%. The major cause for this exceedance is the comparatively high perchlorate contamination of spinach, but also other leaf vegetables, legumes and pineapples, leading to elevated exposure of high consumers. Our calculations reveal that the current provisional intra-Union trade reference level for perchlorate in spinach of 0.2 mg/kg, advocated by the European Commission, is not sufficient to protect high consumers against possible health risks. In order to reduce health risks to a tolerable level for all consumers, lowering of the regulatory maximum perchlorate concentrations is indicated. Moreover, a generally diversified diet can also counteract excessive exposure to perchlorate as well as to other harmful food contaminants.
Assuntos
Exposição Dietética/efeitos adversos , Exposição Ambiental/análise , Análise de Alimentos , Contaminação de Alimentos/análise , Percloratos/efeitos adversos , Poluentes Químicos da Água/análise , Áustria , Humanos , Percloratos/administração & dosagem , Medição de RiscoRESUMO
OBJECTIVE: To conduct a more robust examination of perchlorate exposure on iodide uptake inhibition (IUI) using pooled data from four clinical studies of perchlorate exposure. METHODS: To establish a response threshold for IUI, data were analyzed using segmented linear regression and benchmark dose (BMD) analysis. RESULTS: Segmented linear regression applied to data for 69 subjects representing nine doses identified a breakpoint corresponding to a change in the slope of the dose-response relationship of 3.0âmg/d perchlorate. The estimated BMD for a 20% decrease in iodine uptake was 2.3âmg/d, with a lower 95% confidence interval limit of 1.6âmg/d. CONCLUSIONS: A threshold dose for IUI from perchlorate exposure of 1.6 to 3.0âmg/d (0.021 to 0.038âmg/kgâd) was estimated using two modeling approaches. These estimates are slightly higher than the lowest observed effect level of 0.02âmg/kgâd from the Greer Study.
Assuntos
Radioisótopos do Iodo/metabolismo , Percloratos/farmacologia , Adolescente , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Percloratos/administração & dosagem , Análise de Regressão , Adulto JovemRESUMO
BACKGROUND: This study aimed to establish the changes in the incidence and characteristics of iodine-induced hyperthyroidism (II-Hyper) and iodine-induced hypothyroidism (II-Hypo) in the two-year period before and the 10-year period after the increase in mandatory salt iodization from the previous 10 mg/kg of potassium iodide to 25 mg/kg in 1999. Furthermore, the aim was to determine the duration of treatment in II-Hyper patients, since no data regarding severity and treatment of II-Hyper with respect to iodine supply are available. METHODS: This retrospective study reviewed medical records of 885 Slovenian patients first diagnosed with II-Hyper or II-Hypo between 1998 and 2009 at the Thyroid Department of the University Medical Centre Ljubljana. II-Hyper and II-Hypo were diagnosed by one out of 10 senior internal medicine specialists. The diagnosis was based on an adequate patient history, and laboratory measurements of thyrotropin, thyroid hormones, and thyroid antibodies. In most cases, thyroid ultrasound and thyroid scintigraphy were performed. Demographic characteristics and the type and the duration of treatment were also reviewed. RESULTS: The incidence of II-Hypo was significantly higher after the increase in iodine supply than it was before (p < 0.001). After the increase in iodine supply, the incidence of II-Hyper was significantly lower than before the increase (p < 0.001). Furthermore, the portion of patients with overt hyperthyroidism decreased, predominantly due to the increased proportion of patients with subclinical hyperthyroidism (p = 0.007 and p = 0.015, respectively). The duration of treatment with antithyroid drugs and perchlorate was significantly shorter after the increase in iodine supply than it was before (p = 0.001 and p = 0.002, respectively). A significantly positive correlation between the year of the occurrence of excessive iodine intake (EII)-induced thyroid disease and the duration of treatment with amiodarone was found (R = 0.132; p = 0.048), suggesting that the longer the patients had an adequate iodine supply, the longer they could take amiodarone before EII-induced thyroid disorder developed. CONCLUSIONS: After the increase in iodine supply, a higher incidence of II-Hypo and a lower incidence of II-Hyper were observed than before the increase. Less severe II-Hyper, shorter duration of treatment of II-Hyper, as well as a longer thyroid disease-free period in patients on amiodarone are additional beneficial clinical consequences after the establishment of an adequate iodine supply.
Assuntos
Hipertireoidismo/epidemiologia , Hipotireoidismo/epidemiologia , Iodo/efeitos adversos , Política Nutricional , Cloreto de Sódio na Dieta , Oligoelementos/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antitireóideos/administração & dosagem , Feminino , Humanos , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Incidência , Masculino , Pessoa de Meia-Idade , Percloratos/administração & dosagem , Estudos Retrospectivos , Índice de Gravidade de Doença , Eslovênia/epidemiologia , Fatores de Tempo , Adulto JovemRESUMO
Ensuring adequate iodine intake is important, particularly among women of reproductive age, because iodine is necessary for early life development. Biologically based dose-response modeling of the relationships among iodide status, perchlorate dose, and thyroid hormone production in pregnant women has indicated that iodide intake has a profound effect on the likelihood that exposure to goitrogens will produce hypothyroxinemia. We evaluated the possibility of increasing iodine intake to offset potential risks from perchlorate exposure. We also explored the effect of dietary exposures to nitrate and thiocyanate on iodine uptake and thyroid hormone production. Our modeling indicates that the level of thyroid hormone perturbation associated with perchlorate exposures in the range of current regulatory limits is extremely small and would be overwhelmed by other goitrogen exposures. Our analysis also shows that microgram levels of iodine supplementation would be sufficient to prevent the goitrogenic effects of perchlorate exposure at current regulatory limits among at risk individuals. The human health risks from supplementing drinking water with iodine are negligible; therefore, this approach is worthy of regulatory consideration.
Assuntos
Água Potável/química , Iodo/farmacologia , Percloratos/toxicidade , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Feminino , Feto/metabolismo , Humanos , Iodo/administração & dosagem , Modelos Biológicos , Percloratos/administração & dosagem , Percloratos/química , Gravidez , Tiroxina/sangue , Tiroxina/metabolismoRESUMO
To evaluate the feasibility of urine perchlorate as a biomarker of ammonium perchlorate (AP) exposure and to explore the correlation between the thyroid function indicators and the perchlorate concentrations, a sensitive and selective ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) method was developed to detect perchlorate in urine samples. Rats were orally administrated with different doses of perchlorate. Serum free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) were determined by radioimmunoassays. The results showed that a dose of AP up to 520 mg kg(-1) body weight induced a significant increase of TSH, with a decrease of FT4. Particularly, the levels of urine perchlorate increased dose-dependently on AP exposure from drinking water. The findings highlighted that urine perchlorate may be a useful biomarker for AP environmental exposure.
Assuntos
Exposição Ambiental/análise , Percloratos/administração & dosagem , Percloratos/urina , Compostos de Amônio Quaternário/administração & dosagem , Glândula Tireoide/efeitos dos fármacos , Administração Oral , Animais , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão/métodos , Relação Dose-Resposta a Droga , Homeostase/efeitos dos fármacos , Masculino , Espectrometria de Massas/métodos , Percloratos/toxicidade , Compostos de Amônio Quaternário/toxicidade , Ratos , Ratos Sprague-Dawley , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
Steroid hormones exert profound effects on the development of brain areas controlling complex cognitive function in adulthood. One class, progestins, may contribute by acting on the progestin receptor (PR), which is transiently expressed in a critical layer of developing cortex: the subplate. PR expression in the subplate coincides with the establishment of ongoing cortical connectivity and may play an important organisational role. Identification of the factor(s) that regulate the precise timing of PR expression within subplate may help elucidate the function of PR. Thyroid hormone may interact with hormone response elements within the PR gene. The present study examined the effects of maternal hypothyroidism on levels of PR immunoreactivity (PR-IR) within the foetal subplate. Pregnant rats were made hypothyroid by the administration of methimazole and potassium perchlorate in drinking water. Maternal hypothyroidism significantly decreased PR-IR within the foetal subplate. Using the incorporation of 5-bromo-2'-deoxyuridine (BrDU) during subplate cell neurogenesis (embryonic day 13.5) to determine subplate cell survival in hypothyroid animals, we found that decreases in PR-IR cannot be attributed to significant subplate cell loss but are more likely the result of altered PR expression. Gestational thyroxine replacement to hypothyroid dams prevented the decrease in PR-IR within the subplate. These results identify thyroid hormone as a potential factor in the regulation of PR expression in the developing brain. These results are consistent with the idea that endocrine cross-talk between progesterone and thyroid hormone may be one mechanism by which maternal hypothyroidism alters normal cortical development.
Assuntos
Córtex Cerebral/metabolismo , Hipotireoidismo/metabolismo , Complicações na Gravidez/metabolismo , Receptores de Progesterona/metabolismo , Animais , Córtex Cerebral/embriologia , Feminino , Hipotireoidismo/induzido quimicamente , Imuno-Histoquímica , Metimazol/administração & dosagem , Percloratos/administração & dosagem , Compostos de Potássio/administração & dosagem , Gravidez , Complicações na Gravidez/induzido quimicamente , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Tiroxina/administração & dosagem , Tiroxina/sangueRESUMO
CONTEXT: People being exposed to potentially harmful amounts of radioactive iodine need prophylaxis to prevent high radiation-absorbed doses to the thyroid. OBJECTIVE: Parameters determining the individual protective effect of a pharmacological intervention were investigated. DESIGN AND PARTICIPANTS: Biokinetics of (123)I was evaluated in 27 healthy volunteers (aged 22-46 yr, median 25 yr, in total 48 assessments) twice in a baseline measurement of the undisturbed kinetics and in an intervention assessment 48 h later. INTERVENTIONS: Seven regimens using single doses of potassium iodide (KI) or sodium perchlorate (SP) at different times relative to exposure were compared: 100 mg KI (-24, 2, 8, 24 h), 100 mg SP (2 h), or 1 g SP (2, 8 h). MAIN OUTCOME MEASURES: Different drugs and dosages and the influence of individual parameters of iodine kinetics should be tested. RESULTS: Mean dose reductions for interventions at -24, 2, 8, and 24 h relative to the activity incorporation were 88.7, 59.7, 25.4, and 2.8%, respectively. One gram SP was equally effective as 100 mg KI; residual uptake was observed after 100 mg SP. The individual dose reduction decreased exponentially with the effective half-life of the activity in the blood. Kinetics in subjects older than 40 yr was as assumed in official guidelines for the prophylaxis after nuclear accidents but was faster in younger participants. CONCLUSIONS: Data on the efficacy of thyroid blocking used in the guidelines are adequate for older people but not for young individuals with their typically faster kinetics. SP may be used for thyroid blocking as alternative for individuals with iodine hypersensitivity.
Assuntos
Radioisótopos do Iodo/farmacologia , Percloratos/uso terapêutico , Iodeto de Potássio/uso terapêutico , Compostos de Sódio/uso terapêutico , Glândula Tireoide/metabolismo , Adulto , Fatores Etários , Feminino , Meia-Vida , Humanos , Radioisótopos do Iodo/farmacocinética , Masculino , Pessoa de Meia-Idade , Percloratos/administração & dosagem , Iodeto de Potássio/administração & dosagem , Liberação Nociva de Radioativos , Compostos de Sódio/administração & dosagem , Glândula Tireoide/efeitos dos fármacosRESUMO
Thyroid status was assessed in adult female rhesus monkey breeders at the California National Primate Research Center at the beginning of the breeding season. The 95% confidence intervals for thyrotropin (TSH), thyroxine (T(4)) and triiodothyronine (T(3)) (n = 66-80) were similar to those previously reported in smaller samples of macaque monkeys. Based on human criteria, 10 of 80 monkeys (12%) were hypothyroid (TSH > 2.0 µIU/mL). Because hypothyroxinaemia can be a risk factor in pregnancy, T(4) status was compared with past breeding history, breeding outcome for that season and general health records in a subset of 42 breeders. Age, weight and parity did not differ between monkeys in the lowest T(4) quartile as compared with those in the upper three quartiles. However, T(4) concentrations were significantly associated with the number of missed menstrual cycles during the previous breeding season. In additional work, three healthy lactating rhesus monkeys were given three different doses of environmental contaminant and thyroid iodine uptake inhibitor, ammonium perchlorate (0.006, 0.34, 12.8 mg/kg/day, respectively) in food for two weeks. Thyroid status variables (TSH, T(4), T(3), thyroid radioactive iodine uptake) were then measured. In the monkey receiving the highest perchlorate dose, iodine uptake was suppressed relative to baseline. The study shows the availability of tools to study thyroid status in rhesus monkeys, the variability of thyroid status in the breeder colony and the potential ability of environmental factors to influence thyroid status.
Assuntos
Disruptores Endócrinos/toxicidade , Macaca mulatta/fisiologia , Percloratos/toxicidade , Compostos de Amônio Quaternário/toxicidade , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/sangue , Animais , Disruptores Endócrinos/administração & dosagem , Disruptores Endócrinos/análise , Disruptores Endócrinos/farmacocinética , Feminino , Radioisótopos do Iodo/administração & dosagem , Radioisótopos do Iodo/sangue , Radioisótopos do Iodo/farmacocinética , Macaca mulatta/sangue , Percloratos/administração & dosagem , Percloratos/análise , Percloratos/farmacocinética , Compostos de Amônio Quaternário/administração & dosagem , Compostos de Amônio Quaternário/análise , Compostos de Amônio Quaternário/farmacocinética , Reprodução , Glândula Tireoide/fisiologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
UNLABELLED: (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) scanning precedes radioembolization of the liver to detect extrahepatic shunting to the lung or gastrointestinal tract. Despite strict preventive measures in the production of (99m)Tc-MAA and in scanning protocols, the images frequently show a gastric concentration of free (99m)Tc-pertechnetate, hindering accurate evaluation of the gastroduodenal region. Our aim was to evaluate whether oral administration of sodium perchlorate (NaClO(4)) before (99m)Tc-MAA scanning will improve its accuracy by blocking free (99m)Tc-pertechnetate gastric uptake. METHODS: In 144 patients, 171 diagnostic hepatic angiograms combined with a (99m)Tc-MAA scan were performed; 86 angiograms were performed after oral administration of NaClO(4), and 85 were performed without this premedication. Clinical follow-up, esophagogastroduodenoscopy, and angiography served as reference standards. RESULTS: (99m)Tc-MAA studies showed tracer uptake in the gastric region of 25 patients who did not receive NaClO(4). The uptake was interpreted as a free (99m)Tc-pertechnetate concentration in 21 studies and as a (99m)Tc-MAA accumulation in 4 studies. In 5 patients with a free (99m)Tc-pertechnetate concentration, aberrant vessels were detected in angiographic reexamination, and 3 patients developed gastrointestinal ulcer. In 7 studies, gastric findings viewed pretherapeutically as free (99m)Tc-pertechnetate were retrospectively classified as equivocal. Of the patients receiving NaClO(4), 2 showed gastric accumulation of (99m)Tc-MAA but no equivocal or free (99m)Tc-pertechnetate. Oral administration of NaClO(4) increased the negative predictive value and accuracy of the test concerning the detection of gastric perfusion from 68% and 69%, respectively, to 93% and 94%, respectively. CONCLUSION: Oral administration of NaClO(4) before the test angiogram with (99m)Tc-MAA resulted in effective avoidance of free (99m)Tc-pertechnetate concentration and, consequently, of equivocal findings in the gastroduodenal region. This technique increased test accuracy and reporter confidence, saved time in reviewing the angiograms, and can improve treatment planning and reduce therapeutic side effects.
Assuntos
Embolização Terapêutica , Fígado/metabolismo , Percloratos/administração & dosagem , Percloratos/farmacologia , Compostos de Sódio/administração & dosagem , Compostos de Sódio/farmacologia , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Transporte Biológico/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Humanos , Fígado/efeitos dos fármacos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Cintilografia , Estudos Retrospectivos , Sensibilidade e Especificidade , Pertecnetato Tc 99m de Sódio/metabolismo , Estômago/efeitos dos fármacos , Agregado de Albumina Marcado com Tecnécio Tc 99mRESUMO
Perchlorate can perturb thyroid hormone (TH) homeostasis by competitive inhibition of iodide uptake by the thyroid gland. Until recently, the effects of perchlorate on TH homeostasis were examined by measuring serum concentrations of THs by immunoassay (IA) methods. IA methods are sensitive, but for TH analysis they are compromised by lack of adequate specificity. In this study, we determined the concentrations of six THs: L-thyroxine (T4), 3,3',5-triiodo-L-thyronine (T3), 3,3',5'-triiodo-L-thyronine (rT3), 3,5-diiodo-L-thyronine, 3,3'-diiodo-L-thyronine, and 3-iodo-L-thyronine in the serum of rats administered perchlorate by isotope (¹³C6-T4)-dilution liquid chromatography-tandem mass spectrometry. The method recoveries for THs spiked into a serum matrix were between 97.0% and 115%, with a coefficient of variation of 2.1% to 9.4%. Rats were placed on an iodide-deficient or iodide-sufficient diet for 2.5 months, and for the last 2 weeks of that period they were provided drinking water either without or with perchlorate (10 mg/kg body weight/day). No significant differences in serum concentrations of T3 and T4 were observed between rats given iodide-deficient and iodide-sufficient diets for 2 or 2.5 months. After 24 h of perchlorate exposure, significantly lower concentrations of T3 and T4 were found in the serum of rats administered the iodide-deficient diet but not in rats administered the iodide-sufficient diet. However, after 2 weeks of perchlorate exposure, TH levels in rats fed the iodide-sufficient diet were also significantly lower than those in control rats. Our results suggest that perchlorate affects TH homeostasis and that such effects are more pronounced under iodide-deficient nutrition.
Assuntos
Cromatografia Líquida/métodos , Poluentes Ambientais/farmacologia , Iodetos/metabolismo , Percloratos/farmacologia , Espectrometria de Massas em Tandem/métodos , Tiroxina/sangue , Tiroxina/efeitos dos fármacos , Animais , Iodetos/administração & dosagem , Masculino , Percloratos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Tiroxina/metabolismoRESUMO
INTRODUCTION: Amiodarone-induced thyrotoxicosis (AIT) is a common clinical disorder that may be life threatening and whose clinical manifestations and response to treatment may vary among patients. METHODS: We present three patients treated with amiodarone for atrial fibrillation who developed AIT at least 36 months after beginning the treatment. Thyrotoxicosis worsened the underlying cardiac disorders and was resistant to treatment based on the combination of dexamethasone 8-12 mg/day i.v., thioamides 45 mg/day p.o., beta blockers and potassium perchlorate at doses of 800 to 1000 mg per day p.o. Two of the patients attained sustained euthyroidism after 12 and 32 days of combined treatment, while the third required total thyroidectomy. CONCLUSION: The combination of thioamides with potassium perchlorate is an appropriate form of therapy for AIT in patients resistant to thioamides. The use of this combination should be evaluated in patients with mixed AIT or AIT of unclear etiology.
Assuntos
Amiodarona/efeitos adversos , Percloratos/uso terapêutico , Compostos de Potássio/uso terapêutico , Tireotoxicose/tratamento farmacológico , Acenocumarol/administração & dosagem , Acenocumarol/uso terapêutico , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Amiodarona/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Comorbidade , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Marca-Passo Artificial , Percloratos/administração & dosagem , Compostos de Potássio/administração & dosagem , Tioamidas/administração & dosagem , Tioamidas/uso terapêutico , Hormônios Tireóideos/sangue , Tireoidectomia , Tireotoxicose/sangue , Tireotoxicose/induzido quimicamente , Tireotoxicose/cirurgia , Tireotropina/sangueRESUMO
Amiodarone is a potent antiarrhythmic drug associated with thyroid dysfunction. Its high iodine content causes inhibition of 5'-deiodinase activity. Most patients remain euthyroid. Amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH) may occur depending on the iodine status of individuals and prior thyroid disease. AIT is caused by excess iodine-induced thyroid hormone synthesis (type I AIT) or by destructive thyroiditis (type II AIT). If the medical condition allows it, discontinuation of the drug is recommended in type I AIT. Otherwise, large doses of thioamides are required. Type II AIT is treated with corticosteroids. Mixed cases require a combination of both drugs. Potassium perchlorate has been used to treat resistant cases of type I AIT but use is limited by toxicity. Thyroidectomy, plasmapheresis, lithium, and radioiodine are used in select cases of AIT. AIH is successfully treated with levothyroxine. Screening for thyroid disease before starting amiodarone and periodic monitoring of thyroid function tests are advocated.
Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Hipotireoidismo/induzido quimicamente , Tireotoxicose/induzido quimicamente , Amiodarona/administração & dosagem , Amiodarona/farmacocinética , Antiarrítmicos/administração & dosagem , Antiarrítmicos/farmacocinética , Antitireóideos/uso terapêutico , Continuidade da Assistência ao Paciente , Glucocorticoides/uso terapêutico , Terapia de Reposição Hormonal , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/terapia , Radioisótopos do Iodo/uso terapêutico , Metimazol/uso terapêutico , Percloratos/administração & dosagem , Plasmaferese , Fatores de Risco , Glândula Tireoide/diagnóstico por imagem , Hormônios Tireóideos/sangue , Tireoidectomia , Tireotoxicose/classificação , Tireotoxicose/diagnóstico , Tireotoxicose/terapia , Tiroxina/uso terapêutico , UltrassonografiaRESUMO
Estimates of perchlorate intake by the US population can be derived from either urinary excretion data or through simulation of dietary intake. Estimates from surveys of urinary excretion (NHANES) are subject to substantial uncertainty owing to the small numbers of subjects for which data are currently available. In addition, current excretion estimates are derived from "spot" urine samples and include a component of short-term (intra-day) variability that may give biased estimates of the variability in average daily intakes. Previous dietary estimates have generally not included any contribution from drinking water, owing to a lack of data related to perchlorate concentrations in water supplies. In this paper, we derive simulation (Monte Carlo) estimates of dietary perchlorate intake distributions for reproductive-age women, which include explicit contributions from drinking water, and compare them to estimates based on urinary excretion. Perchlorate concentrations in water were estimated based on measurements from the US Environmental Protection Agency's UCMR1 database, and from other regional studies of perchlorate contamination. We find that including the drinking water contributions in the dietary simulations yields increases in the population's geometric mean perchlorate intake of 3-8 percent, with a conservative maximum of about 24 percent, compared to intakes estimated based on food intake alone. The intake distributions estimated from dietary and water consumption were found to be very similar to estimates based on creatinine-adjusted perchlorate excretion data from the NHANES, except for having lower population variability. When the dietary simulation data were adjusted to include a contribution from short-term variability similar to that in the "spot" urine samples, the variability in the NHANES and diet-derived estimates were found to be very similar. Our analyses indicate that a reasonable upper-bound estimate for the 95th percentile perchlorate intake among women of reproductive age in the US is on the order of 1.5 x 10(-4) mg/kg/day.
Assuntos
Dieta , Ingestão de Líquidos , Exposição Ambiental/análise , Contaminação de Alimentos/análise , Percloratos/administração & dosagem , Percloratos/urina , Abastecimento de Água/análise , Adolescente , Adulto , Simulação por Computador , Creatinina/metabolismo , Creatinina/urina , Bases de Dados Factuais , Exposição Ambiental/estatística & dados numéricos , Feminino , Humanos , Método de Monte Carlo , Inquéritos Nutricionais , Percloratos/toxicidade , Medição de Risco , Estados Unidos , United States Environmental Protection Agency , Abastecimento de Água/normas , Adulto JovemRESUMO
Perchlorate exposure may be higher in infants compared with older persons, due to diet (infant formula) and body weight versus intake considerations. Our primary objective was to quantitatively assess perchlorate concentrations in commercially available powdered infant formulas (PIFs). Secondary objectives were: (1) to estimate exposure in infants under different dosing scenarios and compare them with the perchlorate reference dose (RfD); (2) estimate the perchlorate concentration in water used for preparing PIFs that would result in a dose exceeding the RfD; and (3) estimate iodine intakes from PIFs. We quantified perchlorate levels in three samples (different lot numbers) of reconstituted PIF (using perchlorate-free water) from commercial brands of PIF in each of the following categories: bovine milk-based with lactose, soy-based, bovine milk-based but lactose-free, and elemental (typically consisting of synthetic amino acids). Exposure modeling was conducted to determine whether the RfD might be exceeded in 48 dosing scenarios that were dependent on age, centile energy intake per unit of body weight, body weight percentile, and PIF perchlorate concentration. We obtained three different samples in each of the five brands of bovine- and soy-based PIF, three different samples in each of the three brands of lactose-free PIF, and three different samples in two brands of elemental PIF. The results were as follows: bovine milk-based with lactose (1.72 microg/l, range: 0.68-5.05); soy-based (0.21 microg/l, range: 0.10-0.44); lactose-free (0.27 microg/l, range: 0.03-0.93); and elemental (0.18 microg/l, range: 0.08-0.4). Bovine milk-based PIFs with lactose had a significantly higher concentration of perchlorate (P<0.05) compared with all. Perchlorate was a contaminant of all commercially available PIFs tested. Bovine milk-based PIFs with lactose had a significantly higher perchlorate concentration perchlorate than soy, lactose-free, and elemental PIFs. The perchlorate RfD may be exceeded when certain bovine milk-based PIFs are ingested and/or when PIFs are reconstituted with perchlorate-contaminated water.
Assuntos
Exposição Ambiental/análise , Contaminação de Alimentos/análise , Fórmulas Infantis/química , Percloratos/análise , Fatores Etários , Animais , Peso Corporal/fisiologia , Bovinos , Relação Dose-Resposta a Droga , Exposição Ambiental/estatística & dados numéricos , Feminino , Contaminação de Alimentos/estatística & dados numéricos , Humanos , Lactente , Lactose/análise , Leite Humano/química , Nível de Efeito Adverso não Observado , Percloratos/administração & dosagem , Percloratos/toxicidade , Valores de Referência , Medição de Risco , Leite de Soja/químicaRESUMO
AIMS: Thyroid hormones (TH) play an important role in the development and functional maintenance of the central nervous system. The purpose of this study was to develop a radiotracer method for studying the in vivo efflux transport of iodide liberated by the TH metabolism in the brain. The rationale of our method is as follows: a radioiodinated compound can enter the brain and rapidly release iodide in situ; the iodide efflux rate can be estimated from the clearance of brain radioactivity after disappearance of the iodinated compound. MAIN METHODS: 6-[(125)I]Iodo-9-pentylpurine ([(125)I]9Pe6IP) was designed to enter the brain and release (125)I(-) by the reaction with glutathione and synthesized from the corresponding bromo derivative in a Br/(125)I exchange reaction. The brain kinetics of radioactivity and radioactive metabolites were investigated after intravenous injection of [(125)I]9Pe6IP into mice. The iodide efflux rate was estimated in mice pretreated with perchlorate, an inhibitor of iodide transport from the brain. KEY FINDINGS: High brain uptake (5.3% injected dose/g) was observed at 1 min, and almost complete conversion of [(125)I]9Pe6IP to (125)I(-) occurred 10 min after injection. The (125)I(-) uptake from the blood was negligible. (125)I(-) was eliminated from the brain along a single-exponential curve with a half-life of 6.0 min. Furthermore, dose-dependent inhibition of (125)I(-) efflux was observed in mice pretreated with perchlorate. SIGNIFICANCE: We conclude that 9Pe6IP labeled with (124)I (positron emitter) or (123)I (single-photon emitter) may be useful for studying the in vivo efflux transport of iodide in the brain using nuclear medicine imaging devices.
Assuntos
Encéfalo/metabolismo , Radioisótopos do Iodo/metabolismo , Hormônios Tireóideos/metabolismo , Animais , Ligação Competitiva/efeitos dos fármacos , Ligação Competitiva/fisiologia , Transporte Biológico Ativo/efeitos dos fármacos , Transporte Biológico Ativo/fisiologia , Encéfalo/efeitos dos fármacos , Esquema de Medicação , Humanos , Radioisótopos do Iodo/administração & dosagem , Masculino , Camundongos , Percloratos/administração & dosagem , Percloratos/farmacologia , Permeabilidade/efeitos dos fármacos , Simportadores/antagonistas & inibidores , Hormônios Tireóideos/análiseRESUMO
The US Food and Drug Administration (FDA) has conducted the Total Diet Study (TDS) since 1961, which designed to monitor the US food supply for chemical contaminants, nutritional elements, and toxic elements. Recently, perchlorate was analyzed in TDS samples. Perchlorate is used as an oxidizing agent in rocket propellant, is found in other items (e.g., explosives, road flares, fireworks, and car airbags), occurs naturally in some fertilizers, and may be generated under certain climatic conditions. It has been detected in surface and groundwater and in food. Perchlorate at high (e.g., pharmacological) doses can interfere with iodide uptake into the thyroid gland, disrupting its function. The National Academy of Sciences (NAS) has identified that "the fetuses of pregnant women who might have hypothyroidism or iodide deficiency as the most sensitive population." This study reports on intake estimates of perchlorate and iodine, a precursor to iodide, using the analytical results from the TDS. Estimated average perchlorate and iodine daily intakes as well as the contribution of specific food groups to total intakes were estimated for 14 age/sex subgroups of the US population. The estimated smallest lower bound to the largest upper bound average perchlorate intakes by the 14 age/sex groups range from 0.08 to 0.39 micrograms per kilogram body weight per day (microg/kg bw/day), compared with the US Environmental Protection Agency (EPA) reference dose (RfD) of 0.7 microg/kg bw/day. Infants and children demonstrated the highest estimated intakes of perchlorate on a body weight basis. The estimated average iodine intakes by the 14 age/sex groups reveal a lower bound (ND=0) and upper bound (ND=LOD) range of average intakes from 138 to 353 microg/person/day. Estimated iodine intakes by infants 6-11 months exceed their adequate intake (AI), and intakes by children and adult age/sex groups exceed their relevant estimated average requirement (EAR).