Search

Pregnancy can be complicated by hyperthyroidism or thyrotoxicosis. Diagnosis is founded on an increase in free thyroid hormones and low TSH. The most frequent etiologies are Graves' disease, an autoimmune disease linked to stimulatory anti-TSH receptor antibodies, and non-autoimmune gestational hyperthyroidism linked to the TSH-like activity of the chorionic growth hormone (hCG). During pregnancy, thyrotoxicosis can entail maternal, obstetrical and fetal or neonatal complications. Graves' hyperthyroidism may be responsible for fetal and neonatal hyperthyroidism due to placental transfer of stimulatory anti-TSH receptor antibodies. During pregnancy, treatment of thyrotoxicosis must restore normal thyroid function in the mother without affecting fetal thyroid function. The recent reassessment of the prevalence of teratogenic effects in children of women treated with antithyroid drugs in the first weeks of gestation should orient the care pathway before and during pregnancy for women of child-bearing age with hyperthyroidism linked to Graves' disease.

Objective Agranulocytosis is a rare but serious adverse drug reaction (ADR) of thionamide antithyroid drugs (ATDs). We explored the characteristics of ADRs in patients with hyperthyroidism. Methods This retrospective study included 3558 inpatients with Graves disease treated in a Class A Grade 3 hospital between 2015 and 2019. The clinical presentation and laboratory workup of patients with antithyroid drug (ATD)-induced agranulocytosis was analyzed. Results Agranulocytosis was thought to be caused by ATDs in 36 patients. The hospital length of stay was 12 (10-16) days, and hospitalization costs were approximately $2810.89 ($2156.50-$4164.67). The median duration of ATD therapy prior to agranulocytosis development was 30 (20-40) days. Fever (83.33%) and sore throat (75%) were the most common symptoms as early signs of agranulocytosis. The lowest neutrophil counts were 0.01 (0.00-0.03) × 109/L and 0.14 (0.02-0.29) × 109/L in the methimazole and propylthiouracil groups, respectively (P = .037). The recovery times of agranulocytosis were 9.32 ± 2.89 days and 5.60 ± 4.10 days in the methimazole and propylthiouracil groups, respectively (P = .016). Patients with severe agranulocytosis required a longer time to recover (P Conclusions Patients with agranulocytosis needed a long hospital length of stay and incurred high costs. Methimazole was prone to causing a more serious agranulocytosis than propylthiouracil. High thyroid hormone was unlikely to play a role in adverse drug reactions. Patient education is important.

Objective Radioiodine has been increasingly used to treat hyperthyroidism for many years. Although widely regarded as an effective therapy, radioiodine treatment for hyperthyroidism has been suspected to be associated with the risk of mortality. This study aimed to quantify the mortality outcomes in patients who were treated for hyperthyroidism with radioiodine. Methods Systematic search and meta-analysis were performed to determine the risk of mortality in patients treated with radioiodine for hyperthyroidism. Relevant studies were searched through August 2020 and selected in accordance with the inclusion criteria. Results A total of 13 studies were identified. The summary odds ratios (ORs) showed an increased risk of all-cause mortality in patients who were treated with radioiodine for hyperthyroidism (OR = 1.20; 95% CI = 1.07-1.35). The risk of death attributed to all forms of circulatory, respiratory, and endocrine and metabolic diseases was significantly increased, with summary ORs of 1.23 (95% CI, 1.12-1.35), 1.43 (95% CI, 1.17-1.75), and 2.38 (95% CI, 1.85-3.06), respectively. The summary ORs revealed no significant association between radioiodine treatment for hyperthyroidism and the risk of cancer mortality (OR = 1.03; 95% CI, 0.98-1.09). Radioiodine treatment for hyperthyroidism was not associated with the risk of mortality from breast, respiratory system, gastrointestinal, and genitourinary cancers. Conclusion Radioiodine treatment for hyperthyroidism is associated with the risk of all-cause mortality but not cancer mortality. Future research needs to address the causes of hyperthyroidism, effects of radioiodine therapy, and potential effects of confounding to identify causality.

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 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.

Background Mechanical ventilation (MV) is life saving; yet it may induce severe lung injury and lead to multisystem organ failure and death. Thyroid hormones (THs) promote alveolar fluid clearance and alleviates hypoxia-induced lung injury. Given that the mechanism involved in hypoxia-induced lung injury is different from that of ventilator-induced lung injury, we examined the effects of thyroid function on lung extravascular fluid (LF), aquaporin 5 (AQP 5) expression, and alveolar viscoelasticity (AVE) in mechanically ventilated rat. Methods Hypothyroid (hypo) and hyperthyroid (hyper) animals were generated by administration of metimazole and L-thyroxine, respectively. Lung injury was induced by high-tidal volume MV. The LF was estimated by lung wet weight-to-dry weight ratio assessment. Expression of AQP 5 was evaluated by western blotting and in situ immunohistochemistry. The AVE was judged by elastic lung pressure/volume curve recording. Results Injurious MV significantly reduced lung AQP 5 expression and altered LF and AVE in a thyroid function–dependent manner. Regardless of animals' ventilation mode, hyper state caused significant reductions in LF and lung AQP 5 protein. It also improved AVE irrespective of animals' ventilation mode. The effects of hypo condition on LF, AQP 5 expression, and AVE were in contrast to that of hyper state. Conclusions These data indicate that thyroid function has profound effects on LF, AQP 5, and AVE in mechanically ventilated lungs. Given that the effects of thyroidal status were as prominent as that of injurious MV, we suggest that thyroid function should be considered when patients are to be subjected to MV.

To investigate the long-term outcomes of radioiodine therapy (RIT) for juvenile Graves disease (GD) and the ultrasonographic changes of the thyroid gland.All of 117 juvenile patients (25 males and 92 females, aged 10 to 18lsqb;median 16] years) who had undergone RIT for GD at our clinic between 1999 and 2018 were retrospectively reviewed. Each RIT session was delivered on an outpatient basis. The maximumAt the latest follow-up more than 12 months after RIT (n = 111), the patients' thyroid functions were overt hypothyroidism (91%), subclinical hypothyroidism (2%), normal (5%), or subclinical hyperthyroidism (2%). New thyroid nodules were detected in 9 patients, 4 to 17 years after initial RIT. Patients with newly detected thyroid nodules underwent RIT with lower doses ofOver a median follow-up period of 95 months (range, 4 to 226 months), RIT was found to be effective and safe in juvenile GD. However, cumulative evidence from further studies is required to confirm the long-term safety of RIT for juvenile GD.ATD = antithyroid drug; GD = Graves disease; KI = potassium iodide; LT4 = levothyroxine; MMI = methimazole; PTU = propylthiouracil; RAIU = radio-active iodine uptake; RIT = radioiodine therapy

Objective: To analyze the effects of methimazole (MMI)-containing combination regimens on the thyroid status and relapse rates in patients with Graves hyperthyroidism (GH) using a network meta-analysis to provide guidance for clinical application. Methods: We conducted a literature review, which identified 21 trials for inclusion. The major outcomes were serum free triiodothyronine (FT3) and free thyroxine (FT4) concentrations. The secondary outcome was relapse rate. A network meta-analysis was used to compare multiple regimens to identify the most advantageous regimen. Results: The types of combined drugs included anti-oxidant complexes, selenium, vitamin D3, cholestyramine, risedronate, iodine, potassium bromide, immunosuppressants, and β-adrenergic antagonists. Regarding the FT3 results, the rank probability of the best result showed that potassium bromide (0.897) and vitamin D3 (0.833) had relative advantages in reducing FT3 at the 1-month time point. According to the time trend analysis, compared with the control treatment, cholestyramine and iodine showed advantages in reducing FT3 during the early stage (0 to 3 months). The immunosuppressants showed advantages in reducing FT3 during the late stage (>9 months) but not the early stage. Regarding the FT4 results, potassium bromide had the highest P-score (.965) at the 1-month time point. Iodine and cholestyramine had advantages in reducing FT4 during the early stage. The immunosuppressants had advantages during both the early and late stages. Conclusion: MMI combined with cholestyramine or iodine was shown to regulate serum FT3 and FT4 during the early stage of GH. MMI combined with immunosuppressants had a long-term advantage in FT3/FT4 regulation and reduced the relapse rate. Abbreviations: ATD = antithyroid drug; CI = confidence interval; FT3 = free triiodothyronine; FT4 = free thyroxine; GH = Graves hyperthyroidism; MMI = methimazole; OR = odds ratio; RCT = randomized controlled trial; SMD = standard mean difference; TCM = traditional Chinese medicine.

Background: This study investigated the prognostic parameters and beneficial effects of repeat plasma exchange in children with acute liver failure (ALF). Methods: Twenty-three patients under 18 years of age admitted to National Taiwan University Hospital due to ALF from 2003 to 2016 were included in this retrospective analysis. Results: Among the patients, 11 (48%) had native liver recovery (NLR), 9 (39.1%) died without liver transplant, and 3 (12.9%) received liver transplantation. The NLR group showed a lower proportion of idiopathic cases, lower peak ammonia level, higher peak alpha fetoprotein (AFP) level, and they had plasma exchange fewer times than the other groups. Receiver operating characteristic curve analyses yielded optimal cutoff values of plasma exchange (≤6 times), peak ammonia level (

BackgroundGraves' disease is routinely treated with antithyroid drugs, radioiodine, or surgery, but whether the choice of initial therapy influences long-term outcomes is uncertain. We evaluated cardiovascular morbidity and mortality according to the method and effectiveness of primary therapy in Graves' disease.MethodsIn this retrospective cohort study, we identified patients with hyperthyroidism, diagnosed between Jan 1, 1998, and Dec 31, 2013, from a thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) test register in south Wales, UK, and imported their clinical data into the All-Wales Secure Anonymised Information Linkage (SAIL) Databank (Swansea University, Swansea, UK). Patients with Graves' disease, defined by positive TRAb tests, were selected for the study, and their clinical data were linked with outcomes in SAIL. We had no exclusion criteria. Patients were matched by age and sex to a control population (1:4) in the SAIL database. Patients were grouped by treatment within 1 year of diagnosis into the antithyroid drug group, radioiodine with resolved hyperthyroidism group (radioiodine group A), or radioiodine with unresolved hyperthyroidism group (radioiodine group B). We used landmark Kaplan-Meier and Cox regression models to analyse the association of treatment with the primary outcome of all-cause mortality and the secondary outcome of major adverse cardiovascular events (myocardial infarction, heart failure, ischaemic stroke, or death) with the landmark set at 1 year after diagnosis. We analysed the association between outcomes and concentration of TSH using Cox regression and outcomes and free thyroxine (FT4) concentration using restricted cubic-spline regression models.FindingsWe extracted patient-level data on 4189 patients (3414 [81·5%] females and 775 [18·5%] males) with Graves' disease and 16 756 controls (13 656 [81·5%] females and 3100 [18·5%] males). In landmark analyses, 3587 patients were in the antithyroid drug group, 250 were in radioiodine group A, 182 were in radioiodine group B. Patients had increased all-cause mortality compared with controls (hazard ratio [HR] 1·22, 95% CI 1·05–1·42). Compared with patients in the antithyroid drug group, mortality was lower among those in radioiodine group A (HR 0·50, 95% CI 0·29–0·85), but not for those in radioiodine group B (HR 1·51, 95% CI 0·96–2·37). Persistently low TSH concentrations at 1 year after diagnosis were associated with increased mortality independent of treatment method (HR 1·55, 95% CI 1·08–2·24). Spline regressions showed a positive non-linear relationship between FT4 concentrations at 1 year and all-cause mortality.InterpretationRegardless of the method of treatment, early and effective control of hyperthyroidism among patients with Graves' disease is associated with improved survival compared with less effective control. Rapid and sustained control of hyperthyroidism should be prioritised in the management of Graves' disease and early definitive treatment with radioiodine should be offered to patients who are unlikely to achieve remission with antithyroid drugs alone.FundingNational Institute for Social Care and Health Research, Wales.

Perchlorate, nitrate, and thiocyanate are three well-known sodium iodine symporter inhibitors, however, associations of their individual and concurrent exposure with central thyroid hormones sensitivity remain unclear.To investigate the associations of urinary perchlorate, nitrate, thiocyanate, and their co-occurrence with central thyroid hormones sensitivity among US general adults.A total of 7598 non-pregnant adults (weighted mean age 45.9 years and 52.9% men) from National Health and Nutritional Examination Survey 2007-2012 were included in this cross-sectional study. Central sensitivity to thyroid hormones was estimated with the Parametric Thyroid Feedback Quantile-based Index (PTFQI). Ordinary least-squares regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were performed to examine the associations of three anions and their co-occurrence with PTFQI.The weighted mean values of urinary perchlorate, nitrate, thiocyanate, and perchlorate equivalent concentration (PEC) were 5.48 μg/L, 57.59 mg/L, 2.65 mg/L, and 539.8 μg/L, respectively. Compared with the lowest quartile, the least-square means difference (LSMD) of PTFQI was -0.0516 (LSMD ± SE: -0.0516 ± 0.0185, P 0.01) in the highest perchlorate quartile. On average, PTFQI decreased by 0.0793 (LSMD ± SE: -0.0793 ± 0.0205, P 0.001) between the highest and lowest thiocyanate quartile. Compared with those in the lowest quartile, participants in the highest PEC quartile had significantly decreased PTFQI levels (LSMD ± SE: -0.0862 ± 0.0188, P 0.001). The WQS of three goitrogens, was inversely associated with PTFQI (β: -0.051, 95% CI: -0.068, -0.034). In BKMR model, PTFQI significantly decreased when the levels of three anions were at or above their 60th percentiles compared to the median values.Higher levels of urinary perchlorate, thiocyanate, and co-occurrence of three goitrogens were associated with increased central thyroid hormones sensitivity among US general adults. Further studies are warranted to replicate our results and elucidate the underlying causative mechanistic links.

Hypothyroidism causes an imbalance in antioxidant and pro-oxidants criteria in the brain and enhances the concentration of reactive oxygen species (ROS), and neuronal damage has been observed following an excessive ROS. The main purpose of this study was to examine the preventive effect of vitamin C on hypothyroidism associated neuronal damage in the hippocampus of neonatal and juvenile rats. Pregnant rats after delivery of their pups were randomly divided into four groups and treated with (1) normal drinking water as a control group, (2) Propylthiouracil (PTU) 0.005% added to drinking water, (3-, 4) PTU + Vit C 10 mg/ kg and PTU + Vit C 100 mg/ kg to drinking water. Treatment was carried out during rat's lactation period until to the postnatal day (PND) 60. To assess the histological and stereological changes that occur in this study, brains of 5 male pups were extracted. The number of dark neurons and apoptotic cells in the hippocampal sub-regions of PTU group was significantly greater than the control group's hippocampal sub-regions. In addition, hypothyroidism induced a reduction in the hippocampal volume and increased the numerical density and the total amount of dark neurons. The vitamin C only dose of 100 mg/kg significantly reduced the number of dark neurons and apoptotic cells (P 0.01) and considerably weakened the influence of hypothyroidism on the volume reduction of the hippocampus (P 0.05). The current study suggested that vitamin C administration has a possibility to prevent hippocampal neuronal damage caused by neonatal and juvenile hypothyroidism in rats.

Hyperthyroidism in children is a rare heterogeneous syndrome characterized by excessive thyroid hormone production. Its manifestations differ according to disease severity. For all forms of hyperthyroidism, treatment aims to restore a euthyroid state, enabling the child to demonstrate appropriate metabolism, growth, and neurocognitive development. Graves' disease is the most frequent cause of hyperthyroidism in children. Treatment modalities include antithyroid drugs, with the advantage that prolonged treatment for several years can be followed by freedom from medical intervention in about 40-50% of cases. It may also be treated with radioactive iodine or, less frequently, thyroidectomy, these more radical treatments both necessitating subsequent lifelong levothyroxine treatment. Particular care is required in the management of pregnant women with Graves' disease. Fetal and neonatal forms of hyperthyroidism are transient and rare, but nevertheless serious. Here, we provide an overview of the best approach to hyperthyroidism diagnosis and management, from fetal development to adolescence.

Thyroid hormone (TH) is critical for many aspects of neurodevelopment and can be disrupted by a variety of environmental contaminants. Sensory systems, including audition and vision are vulnerable to TH insufficiencies, but little data are available on visual system development at less than severe levels of TH deprivation. The goal of the current experiments was to explore dose-response relations between graded levels of TH insufficiency during development and the visual function of adult offspring. Pregnant Long Evans rats received 0 or 3 ppm (Experiment 1), or 0, 1, 2, or 3 ppm (Experiment 2) of propylthiouracil (PTU), an inhibitor of thyroid hormone synthesis, in drinking water from gestation day (GD) 6 to postnatal day (PN) 21. Treatment with PTU caused dose-related reductions of serum T4, with recovery on termination of exposure, and euthyroidism by the time of visual function testing. Tests of retinal (electroretinograms; ERGs) and visual cortex (visual evoked potentials; VEPs) function were assessed in adult offspring. Dark-adapted ERG a-waves, reflecting rod photoreceptors, were increased in amplitude by PTU. Light-adapted green flicker ERGs, reflecting M-cone photoreceptors, were reduced by PTU exposure. UV-flicker ERGs, reflecting S-cones, were not altered. Pattern-elicited VEPs were significantly reduced by 2 and 3 ppm PTU across a range of stimulus contrast values. The slope of VEP amplitude-log contrast functions was reduced by PTU, suggesting impaired visual contrast gain. Visual contrast gain primarily reflects function of visual cortex, and is responsible for adjusting sensitivity of perceptual mechanisms in response to changing visual scenes. The results indicate that moderate levels of pre-and post-natal TH insufficiency led to alterations in visual function of adult rats, including both retinal and visual cortex sites of dysfunction.

Few studies on hyperthyroidism treatment have been reported in the past 3 decades. We used a nationwide population-based database to evaluate the current practices and management of hyperthyroidism in Taiwan.This retrospective study included a random selection of 1 million people in Taiwan between 2004 and 2010. We identified patients with hyperthyroidism who received antithyroid drugs (ATD), radioactive iodine (RAI), or surgery. We calculated the proportions and treatment trends of those 3 treatment options annually. A Poisson regression model was used to determine whether trends changed.The prevalence of overt hyperthyroidism in Taiwan steadily increased from 2,666 (0.27%) in 2004 to 3,464 (0.37%) in 2010. The incidence of hyperthyroidism (per 1,000 persons) also increased from 0.97 in 2004 to 1.06 in 2010. The major proportion of hyperthyroidism in this study was Graves disease (95%), followed by toxic nodular goiter (2%), and other causes (3%). ATD is the most commonly used (96-97%) treatment for hyperthyroidism, followed by surgery (2-3%) and RAI (1%). There was a significant decreasing trend for surgery, from 2.9% in 2004 to 2% in 2010, especially in female patients (3.3% in 2004 to 2.3% in 2010, P.01) and patients younger than 40 (3.8% in 2004 to 2.9% in 2010, P.01). Meanwhile, the proportions of ATD and RAI remained unchanged. The most common ATD prescription was methimazole (45-50%), followed by propylthiouracil (30-32%) and carbimazole (19-21%).Between 2004 and 2010, ATD was the treatment of choice in Taiwan, followed by surgery and RAI.ATA = American Thyroid Association; ATD = antithyroid drug; LHID2005 = Longitudinal Health Insurance database 2005 dataset; NHI = National Health Insurance; RAI = radioactive iodine.

Aims High fat diet consumes and thyroid hormones (THs) disorders may affect nutrients metabolism, but their impact on the absorptive epithelium, the first place of nutrients access, remains unknown. Our aim was to evaluate the intestinal morphology and nutrients transporters content in mice fed standard (LFD) or high fat (HFD) diets in hypo or hyperthyroidism-induced condition. Material and methods C57BL/6 male mice fed LFD or HFD diets for 12 weeks, followed by saline, PTU (antithyroid drug) or T3 treatment up to 30 days. The mice were euthanized and proximal intestine was removed to study GLUT2, GLUT5, PEPT1, FAT-CD36, FATP4, NPC1L1 and NHE3 distribution by Western blotting. Since PPAR-a is activated by fatty acids, which is abundant in the HFD, we also evaluated whether PPAR-a affects nutrients transporters. Thus, mice were treated with fenofibrate, a PPAR-a agonist. Key findings HFD decreased GLUT2, PEPT1, FAT-CD6 and NPC1L1, but increased NHE3, while GLUT5 and FATP4 remained unaltered. THs did not alter distribution of nutrients transporters neither in LFD nor in HFD groups, but they increased villi length and depth crypt in LFD and HFD, respectively. Fenofibrate did not affect content of nutrients transporters, excluding PPAR-a involvement on the HFD-induced changes. Significance We assume that chronic HFD consumption reduced most of the nutrients transporters content in the small intestine of mice, which might limit the entrance of nutrients and gain weight. Since NHE3 promotes sodium absorption, and it was increased in HFD group, this finding could contribute to explain the hypertension observed in obesity.

Neonatal thyrotoxicosis (hyperthyroidism) is less prevalent than congenital hypothyroidism; however, it can lead to significant morbidity and mortality if not promptly recognized and adequately treated. Most cases are transient, secondary to maternal autoimmune hyperthyroidism (Graves disease [GD]). This article summarizes recommendations for screening and management of hyperthyroidism in both the fetal and neonatal periods, with a focus on neonatal thyrotoxicosis secondary to maternal GD. Early monitoring and treatment are crucial for optimizing short-term and long-term patient outcomes.

Introduction Graves’ disease (GD) is an autoimmune thyroid disease, common in adults but rare in children. The best therapeutic approach remains controversial. Objectives To ascertain the current treatment of pediatric GD in Portugal and to assess the clinical and biochemical factors that determine definitive/long-term remission after treatment with antithyroid drugs (ATDs). Patients and methods A retrospective analysis of data about pediatric GD treatment collected from a nationwide survey conducted by the Portuguese Society of Pediatric Endocrinology and Diabetology from May to August 2013. Population was categorized based on sex, age, use of ATDs, dosage, treatment duration, adverse reactions, thyrotropin receptor-stimulating antibody (TRAB) titer, remission and remission/relapse rates, and definitive treatment, and divided into group A (with ongoing treatment) and group B (with treatment stopped). Group B was subdivided into ‘Remission’, ‘Remission + relapse’ and ‘No remission’ subgroups based on the course of disease. The same parameters were compared between both groups. Results Survey response rate was 77%; 152 subjects, 116 female, mean age at diagnosis 11.23 ± 3.46 years. They all started treatment with ATDs, 70.4% with thiamazole, with a mean treatment duration of 32.38 ± 28.29 months, and 5.9% had adverse effects. Remission rate was 32.6%. Lower age at diagnosis correlated with higher remission rates. Treatment duration was longer when propylthiouracil was used. Initial TRAB titer was significantly higher in the ‘No remission’ group. Surgery and radioiodine were used as second-line treatments. Conclusion Our study results were similar to those reported in the literature. Age and TRAB titer were identified as potential clinical and laboratory determinants of remission. Based on risk/benefit analysis, it was concluded that treatment should be individualized based on age, accessibility to treatments, and physician's experience.

Thyroid hormones play an instrumental role in the development of the central nervous system. During early development, the fetus is dependent on maternal thyroid hormone production due to the dysfunction of its own thyroid gland. Thus, maternal thyroid dysfunction has been shown to elicit significant abnormalities in neural development, neurochemistry, and behavior in offspring. Previous reports have suggested that human maternal hypothyroidism may increase the chances of having children with autism spectrum disorder and attention-deficit/hyperactivity disorder. However, very few studies have evaluated social behaviors in animal models of perinatal hypothyroidism. To evaluate the possibility that hypothyroidism during development influences the expression one of the most commonly observed non-reproductive social behaviors, juvenile play, we used the validated rat model of perinatal hypothyroidism by methimazole administration (MMI; 0.025% in drinking water) from GD12-PD23. Control animals had regular drinking water. During adolescence (PD33-35), we tested subjects for juvenile play behavior by introducing them to a same-sex, unfamiliar (since weaning) littermate for 30 min. Play behaviors and other behaviors (sleep, social contact, locomotion) were then scored. MMI-treated subjects played more than twice as much as control animals, and the increase in some behaviors was particularly dramatic in males. Locomotor and other affiliative social behaviors were unaffected. These data suggest that perinatal hypothyroidism may alter the organization of the neural networks regulating play behaviors, but not other social behaviors. Moreover, this implicates perinatal hypothyroidism as a potential etiological factor in the development of neurobehavioral disorders, particularly those characterized by heightened social interactions and impulsivity.

A 47-year-old man presented to our emergency department (ED) with limbs weakness for 2 h. His heart rate was 127 beats per minute and blood pressure was 95/49 mm Hg. He found weakness of limbs after 4-h sleep. Physical examinations revealed that the muscle strength of upper limbs is 3/5, and lower limbs are 2/5. Electrocardiogram (ECG) revealed wide QRS complex, monomorphic ventricular tachycardia (VT) with ST-segment depression and long QT interval. Serum potassium level was extremely low as 1.0 mEq/L. This led to periodic hypokalemic paralysis. Due to severe hypokalemia with possible atrioventricular block, the patient was admitted to the intensive care unit. During hospitalization, his potassium level returned to 5.1 mEq/L on the first day. He had a low level of thyroid stimulating hormone (TSH) of0.03 micro-IU/mL (normal range: 0.25-4.00) and a high free thyroxine (T4) level of 2.43 ng/dL (normal range: 0.89-1.79 ng/dL). Therefore, hyperthyroidism was diagnosed, and 5 mg of methimazole was administered twice a day. The patient was discharged on the seventh day after admission. The final diagnosis is thyrotoxic periodic paralysis (TPP), also as known as nocturnal paralysis or night palsy.

Hyperthyroidism (HT) is characterized by an intense metabolic impact which affects the lipid, carbohydrate and amino acids metabolism, with increased resting energy expenditure and thermogenesis. Metabolomics is a new comprehensive technique that allows to capture an instant metabolic picture of an organism, reflecting peculiar molecular and pathophysiological states. The aim of the present prospective study was to identify a distinct metabolomic profile in HT patients using 1H NMR spectroscopy before and after antithyroid drug treatment. This prospective study included 15 patients (10 female, 5 male) who were newly diagnosed hyperthyroidism. A nuclear magnetic resonance (1H NMR) based analysis was performed on plasma samples from the same patients at diagnosis (HypT0) and when they achieved euthyroidism (HypT1). The case groups were compared with a control group of 26 healthy volunteers (C). Multivariate statistical analysis was performed with Partial Least Squares-Discriminant Analysis (PLS-DA). PLS-DA identified a distinct metabolic profile between C and untreated hyperthyroid patients (R2X 0.638, R2Y 0.932, Q2 0.783). Interestingly, a significant difference was also found between C and euthyroid patients after treatment (R2X 0.510, R2Y 0.838, Q2 0.607), while similar cluster emerged comparing HypT0 vs HypT1 patients. This study shows that metabolomic profile is deeply influenced by hyperthyroidism and this alteration persists after normalization of thyrotropin (TSH) and free thyroid hormone (FT3, FT4) concentration. This suggests that TSH, FT3 and FT4 assays may not be insufficient to detect long lasting peripheral effects of the thyroid hormones action. Further studies are needed to clarify whether and to what extent the evaluation of metabolomics profile may provide relevant information in the clinical management of hyperthyroidism.

The effects of two drugs containing the synthetic thyroid hormone levothyroxine (LEV) and an anti-thyroid drug containing propylthiouracil (PTU) on the three early life stages of Xenopus laevis were evaluated with the Frog Embryo Teratogenesis Assay-Xenopus, Tadpole Toxicity Test, and Amphibian Metamorphosis Assay using biochemical and morphological markers. Tested drugs caused more effective growth retardation in stage 8 embryos than stage 46 tadpoles. Significant inhibition of biomarker enzymes has been identified in stage 46 tadpoles for both drugs. AMA test results showed that LEV-I caused progression in the developmental stage and an increase in thyroxine level in 7 days exposure and growth retardation in 21 days exposure in stage 51 tadpoles. On the other hand, increases in lactate dehydrogenase activity for both drugs in the AMA test may be due to impacted energy metabolism during sub-chronic exposure. These results also show that the sensitivity and responses of Xenopus laevis at different early developmental stages may be different when exposed to drugs.

There is poor evidence for an association between thyroidal state, feeding and appetite regulation in fish. We assessed how an altered thyroid state influences feeding behavior, food intake and expression of hypothalamic appetite-regulating peptides (Klotho-α and Klotho-β; orexin, OX; cholecystokinin, CCK; agouti-related peptide, AgRP; cannabinoid receptor 1, CB1) in goldfish. We also measured the expressions of hypothalamic, pituitary and liver transcripts that regulate the thyroid [thyrotropin-releasing hormone (TRH), thyrotropin-releasing hormone receptor (TRH-R) type 1, thyroid stimulating hormone beta (TSHβ), deiodinases (DIO2, DIO3), UDP-glucuronosyltransferase (UGT1A1), thyroid receptor alpha and beta (TRα, TRβ)], and circulating levels of total thyroxine (tT4) and total triiodothyronine (tT3). Goldfish were implanted with propylthiouracil (PTU) or T4 osmotic pumps for 12 days. T4- treatment increased feeding behavior but not food intake, increased central TSHβ and DIO2, and hepatic DIO2 transcript expression and increased central DIO3 mRNA. Under hyperthyroid conditions, hypothalamic Klotho and CCK expressions were downregulated, suggesting an increased metabolic state and a hypothalamic response to regulate energy balance. AgRP, OX and CB1 were not affected by T4 treatment. PTU had no effect on any of the parameters examined, suggesting it is not a sensitive thyroid inhibitor in fish. Overall, we show that unlike in mammals, hyperthyroid conditions in goldfish do not lead to an increased desire or need to consume food, furthering evidence for a weak link between the thyroid and appetite.

Resveratrol is a natural polyphenol with antioxidant, anti-inflammatory, and antiproliferative properties. We have shown previously that resveratrol decreases sodium/iodide symporter expression and iodide uptake in thyrocytes, both in vitro and in vivo. In the present study, we further investigated the effects of resveratrol, with evaluation of the expression of additional thyroid-specific genes in the FRTL-5 rat thyroid cell line: thyroglobulin, thyroid peroxidase, TSH receptor, Nkx2-1, Foxe1 and Pax8. We observed decreased expression of these genes in FRTL-5 cells treated with 10 μM resveratrol. The effects of resveratrol was further evaluated in vivo using Sprague-Dawley rats treated with resveratrol 25 mg/kg body weight intraperitoneally, for 60 days. No clinical signs of hypothyroidism were seen, although the treated rats showed significant increase in thyroid size. Serum TSH and thyroid hormone levels were in the normal range, with significantly higher TSH seen in resveratrol-treated rats, compared with control rats. Histological and immunohistochemical analyses confirmed increased proliferative activity in the thyroid from resveratrol-treated rats. These data suggest that resveratrol acts as a thyroid disruptor and a goitrogen, which indicates the need for caution as a supplement and for therapeutic uses.

Technetium thyroid uptake (TTU) is not inhibited by antithyroid drugs (ATD) and reflects the degree of thyroid stimulation. We intended to predict the relapse rate from hyperthyroidism based on TTU measurement.Out of 44 initially enrolled subjects, 38 patients aged 41.6 ± 14.6 with Graves disease (duration: 84 ± 78 months) completed the study. TTU was performed with 40-second imaging of the neck and mediastinum 20 minutes after injection of 1 mCi technetium-99m pertechnetate. TTU was measured as the percentage of the count of activity accumulated in the thyroidal region minus the mediastinal background uptake to the count of 1 mCi technetium-99m under the same acquisition conditions. Then methimazole was stopped and patients were followed. The optimal TTU cutoff value for Graves relapse prediction was calculated using Youden's J statistic.Hyperthyroidism relapsed in 11 (28.9%) patients 122 ± 96 (range: 15-290) days post-ATD withdrawal. The subjects in remission were followed for 209 ± 81 days (range: 88-390). TTU was significantly higher in patients with forthcoming relapse (12.0 ± 8.0 vs. 3.9 ± 2.0, P = .007). The difference was significant after adjustment for age, sex, history of previous relapse, disease duration, and thyroid-stimulating hormone (TSH) levels before withdrawal. The area under the receiver operative characteristic (ROC) curve was 0.87. The optimal TTU cutoff value for classification of subjects with relapse and remission was 8.7 with sensitivity, specificity, and positive and negative predictive value of 73%, 100%, 100%, and 90%, respectively (odds ratio [OR] = 10.0; 95% confidence interval [CI]: 3.4-29.3).TTU evaluation in hyperthyroid patients receiving antithyroid medication is an accurate and practical method for predicting relapse after ATD withdrawal.ATD = antithyroid drugs RIU = radio-iodine uptake TSH = thyroid-stimulating hormone TSI = thyroid-stimulating immunoglobulin TTU = technetium thyroid uptake.

Perinatal hypothyroidism causes serious damage to auditory functions that are essential for vocalization development. In rat pups, perinatal hypothyroidism potentially affects the development of ultrasonic vocalization (USV) as a result of hearing deficits. This study examined the effect of perinatal hypothyroidism on the development of USVs in rat pups. Twelve pregnant rats were divided into three groups and treated with the anti-thyroid drug methimazole (MMI) via drinking water, from gestational day 15 to postnatal day (PND) 21. The MMI concentration (w/v) was 0% (control group), 0.01% (low-dose group), or 0.015% (high-dose group). After birth, the pups were individually separated from the dam and littermates on PNDs 5, 10, 15, and 20, and their USVs were recorded for 5 min. On PNDs 5 and 10, compared with the control group, the low- and high-dose groups exhibited reductions of both frequency modulated and downward USVs. On PND 15, however, the low- and high-dose groups displayed increases in number, duration, and amplitude of USVs compared with those in the control group. Lower body weights were observed for the low- and high-dose groups than for the control group. Total thyroxine concentrations in plasma were dose-dependently reduced. The onset of auditory functions appeared on PNDs 11-14. Thus, the rat pups were unable to hear externally produced USVs before PND 11. USVs emitted on PNDs 5 and 10 might have been spontaneous and independent of the pups' own or littermate-emitted USVs. The developmental retardation of vocalization-related organs or muscles might underlie the acoustic alterations of USVs on PNDs 5 and 10. The greater number, duration, and amplitude of USVs on PND 15, after which the hearing onset occurred, suggested that the elevation of auditory thresholds occurred as a result of hearing deficits in the low- and high-dose groups. Perinatal hypothyroidism appears to have caused acoustic alterations in the USV development. (C) 2016 Elsevier B.V. All rights reserved.

In this study, a recombinant thyroid receptor (TR) gene yeast assay combined with Monte Carlo simulation were used to evaluate and characterize soil samples collected from Jilin (China) along the Second Songhua River, for their ant/agonist effect on TR. No TR agonistic activity was found in soils, but many soil samples exhibited TR antagonistic activities, and the bioassay-derived amiodarone hydrochloride equivalents, which was calculated based on Monte Carlo simulation, ranged from not detected (N.D.) to 35.5μg/g. Hydrophilic substance fractions were determined to be the contributors to TR antagonistic activity in these soil samples. Our results indicate that the novel calculation method is effective for the quantification and characterization of TR antagonists in soil samples, and these data could provide useful information for future management and remediation efforts for contaminated soils.

Methimazole is the most frequently prescribed antithyroid agent. On the other hand, several cases of liver injury are attributed to this drug. The mechanism of methimazole-induced liver injury is obscure. Hepatocytes mitochondria seem to be a target for methimazole cytotoxicity. Current investigation aimed to evaluate the effects of methimazole on the hepatocytes mitochondria in different experimental models. In the in vivo model, methimazole (100, 200 and 400 mg/kg, i.p) was administered to mice and liver mitochondria were isolated and assessed. In the in vitro experiments, intact isolated liver mitochondria were incubated with increasing methimazole concentrations (10 μM–100 mM). It was found that methimazole decreased liver mitochondrial ATP and glutathione, increased mitochondrial swelling, lipid peroxidation and reactive oxygen species (ROS), and collapsed mitochondrial membrane potential when administered to mice. Paradoxically, methimazole not only caused no significant injury toward isolated liver mitochondria in vitro but improved mitochondrial function and protected this organelle. The differences between two investigated models in the current study might be associated with drug bioactivation and reactive metabolites formation. These findings suggest mitochondrial dysfunction as a mechanism for methimazole-induced liver injury. Moreover, methimazole seems to be a novel mitochondrial protecting agent in vitro .

The sodium iodide-symporter (NIS) mediates uptake of iodide into thyroid follicular cells. This key step in thyroid hormone synthesis is inhibited by perchlorate, thiocyanate (SCN) and nitrate (NO3) anions. When these exposures occur during pregnancy the resulting decreases in thyroid hormones may adversely affect neurodevelopment of the human fetus. Our objectives were to describe and examine the relationship of these anions to the serum thyroid indicators, thyroid stimulating hormone (TSH) and free thyroxine (FT4), in third trimester women from the initial Vanguard Study of the National Children's Study (NCS); and to compare urine perchlorate results with those in pregnant women from the National Health and Nutritional Examination Survey (NHANES). Urinary perchlorate, SCN, NO3, and iodine, serum TSH, FT4, and cotinine were measured and a food frequency questionnaire (FFQ) was administered to pregnant women enrolled in the initial Vanguard Study. We used multiple regression models of FT4 and TSH that included perchlorate equivalent concentration (PEC, which estimates combined inhibitory effects of the anions perchlorate, SCN, and NO3 on the NIS). We used multiple regression to model predictors of each urinary anion, using FFQ results, drinking water source, season of year, smoking status, and demographic characteristics. Descriptive statistics were calculated for pregnant women in NHANES 2001-2012. The geometric mean (GM) for urinary perchlorate was 4.04µg/L, for TSH 1.46mIU/L, and the arithmetic mean for FT4 1.11ng/dL in 359 NCS women. In 330 women with completed FFQs, consumption of leafy greens, winter season, and Hispanic ethnicity were significant predictors of higher urinary perchlorate, which differed significantly by study site and primary drinking water source, and bottled water was associated with higher urinary perchlorate compared to filtered tap water. Leafy greens consumption was associated with higher urinary NO3 and higher urinary SCN. There was no association between urinary perchlorate or PEC and TSH or FT4, even for women with urinary iodine

Thyroid hormones (TH) are critical for brain development and insufficiencies can lead to structural abnormalities in specific brain regions. Administration of the goitrogen propylthiouracil (PTU) reduces TH production by inhibiting thyroperoxidase (TPO), an enzyme that oxidizes iodide for the synthesis of TH. TPO activity is iron (Fe)-dependent and dietary iron deficiency (FeD) also reduces circulating levels of TH. We have previously shown that modest degrees of TH insufficiency induced in pregnant rat dams alters the expression of TH-responsive genes in the cortex and hippocampus of the neonate, and results in the formation of a subcortical band heterotopia (SBH) in the corpus callosum (Royland et al., 2008, Bastian et al., 2014, Gilbert et al., 2014). The present experiment investigated if FeD alone was sufficient to induce a SBH or if FeD would augment SBH formation at lower doses of PTU. One set of pregnant rats was administered 0, 1, 3, or 10ppm of PTU via drinking water starting on gestational day (GD) 6. FeD was induced in a 2nd set of dams beginning on GD2. A third set of dams received the FeD diet from GD2 paired with either 1ppm or 3ppm PTU beginning on GD6. All treatments continued until the time of sacrifice. On PN18, one female pup from each litter was sacrificed and the brain examined for SBH. We observed lower maternal, PN2 and PN18 pup serum T4 in response to PTU. FeD reduced serum T4 in pups on PN16, but did not affect serum T4 in dams or PN2 pups. Neither did FeD in combination with PTU alter T4 levels in dams on PN18 or pups on PN2 compared to PTU treatment alone. By PN16, however more severe T4 reductions were observed in pups when FeD was combined with PTU. SBH increased with increasing dosage of PTU, but counter to our hypothesis, no SBH was detected in the offspring of FeD dams. As such, T4 levels in dams and newborn pups rather than older neonates appear to be a better predictor SBH associated with TH insufficiency. These data indirectly support previous work indicating prenatal TH insufficiency but not postnatal TH insufficiency in offspring is required for SBH formation.

The objective of this work is to report our experience with (131)I therapy without recent antithyroid drug (ATD) pretreatment for refractory severe hyperthyroidism complicated by hyperbilirubinemia due to hepatic dysfunction.Five patients with refractory severe hyperthyroidism were treated with (131)I at 90 to 120 μCi/g-thyroid (total activity, 6.2 to 10.1 mCi). The patients previously had received ATD treatment from 2 months to 12 years and discontinued ATDs from 2 months to 4 years before (131)I treatment due to treatment failure or severe jaundice. Prior to (131)I therapy, the patients were asked to take a low-iodine diet and were treated with bisoprolol fumarate, digoxin, furosemide, S-adenosylmethionine, polyene phosphatidylcholine, and plasma exchange as supportive treatment for related clinical conditions. Four of the patients also received lithium carbonate in conjunction with their (131)I treatment. The patients were followed for 4 to 9 years after (131)I therapy.After (131)I treatment, jaundice disappeared completely within 3 to 4 months in all patients, and liver function tests returned to normal. Concurrent atrial fibrillation and heart failure, leukopenia and thrombocytopenia, or thrombocytopenia and left cardiac enlargement improved remarkably in 3 patients during the follow-up period. Three to 45 months after (131)I treatment, hypothyroidism was noted in the patients and they were treated with L-thyroxine replacement therapy.(131)I therapy without recent ATD pretreatment for refractory severe hyperthyroidism complicated by serious jaundice appears to be safe and effective, with good long-term results. It may be the preferred therapy for such patients and should be used as early as possible.

Developmental disorders such as anxiety, autism, and attention deficit hyperactivity disorders have been linked to exposure to polychlorinated biphenyls (PCBs), a ubiquitous anthropogenic pollutant. The zebrafish is widely recognized as an excellent model system for assessing the effects of toxicant exposure on behavior and neurodevelopment. In the present study, we examined the effect of sub-chronic embryonic exposure to the PCB mixture, Aroclor (A) 1254 on anxiety-related behaviors in zebrafish larvae at 7 days post-fertilization (dpf). We found that exposure to low concentrations of A1254, from 2 to 26 hours post-fertilization (hpf) induced specific behavioral defects in two assays. In one assay with intermittent presentations of a moving visual stimulus, 5 ppm and 10 ppm PCB-exposed larvae displayed decreased avoidance behavior but no significant differences in thigmotaxis or freezing relative to controls. In the other assay with intermittent presentations of a moving visual stimulus and a stationary visual stimulus, 5 ppm and 10 ppm PCB-exposed larvae had elevated baseline levels of thigmotaxis but no significant differences in avoidance behavior relative to controls. The 5 ppm larvae also displayed higher terminal levels of freezing relative to controls. Collectively, our results show that exposure to ecologically valid PCB concentrations during embryonic development can induce functional deficits and alter behavioral responses to a visual threat.

This study examined the effects thyroid-active compounds during early development on body morphology of Zebrafish (Danio rerio). Three-day postfertilization (dpf) larvae were exposed to goitrogen [methimazole (MZ, 0.15mM)], combination of MZ (0.15mM) and thyroxine (T4, 2nM), T4 (2nM), or control (reconstituted water) treatments until 33dpf and subsequently maintained in reconstituted water until 45dpf. Samples were taken at 33 and 45dpf for multivariate analysis of geometric distances between selected homologous landmarks placed on digital images of fish, and for histological assessment of thyrocytes. Body mass, standard length, and pectoral fin length were separately measured on remaining fish at 45dpf. Histological analysis confirmed the hypothyroid effect (increased thyrocyte height) of MZ and rescue effect of T4 co-administration. Geometric distance analysis showed that pectoral and pelvic fins shifted backward along the rostrocaudal axis under hypothyroid conditions at 45dpf and that T4 co-treatment prevented this shift. Pectoral fin length at 45dpf was reduced by exposure to MZ and rescued by co-administration of T4, but it was not associated with standard length. Methimazole caused a reduction in body mass and length at 45dpf that could not be rescued by T4 co-administration, and non-thyroidal effects of MZ on body shape were also recognized at 33 and 45dpf. Alterations in the length and position of paired fins caused by exposure to thyroid-disrupting chemicals during early development, as shown here for Zebrafish, could affect physical aspects of locomotion and consequently other important organismal functions such as foraging, predator avoidance, and ultimately survival and recruitment into the adult population. Results of this study also suggest the need to include rescue treatments in endocrine disruption studies that rely on goitrogens as reference for thyroid-mediated effects.

Hepatotoxicity is a rare but serious side effect of antithyroid drug (ATI) therapy in Graves’ disease patients. Cessation of ATI drug is needed in most of the patients if liver enzymes highly elevated or in case of agranulocytosis. Permanent therapy, surgery or radioactive iodine ablation are the treatment choices to ensure euthyroidism in active Graves’ disease patients. Therapeutic plasma exchange (TPE) can be an option to ensure euthyroidism, especially in patients scheduled for urgent surgery. In the present study, we present consecutive five cases of methimazole related severe hepatotoxicity that underwent TPE before thyroid surgery. The median number of apheresis sessions was 3 (range: 2–5). Free triiodothyronine (FT3) 65–83 %, free thyroxine (FT4) 22–66 %, thyrotropin receptor antibodies (TRAB) 55–96 % decreases were observed. All patients underwent total thyroidectomy. TPE is an effective method to reduce serum FT3, FT4, TRAB levels in the short term to provide better thyroid hormone status before urgent surgery in ATI induced toxic hepatitis patients.

Antithyroid drugs (ATDs) are the first-line treatment for Graves' disease (GD). A common problem with ATD treatment is the high relapse rate after drug withdrawal. The goal of this study was to analyze the influencing factors for the relapse of GD patients treated with ATD by using a systematic review and meta-analysis, provide some predictive indexes for the susceptibility of GD recurrence, and then further explore some useful methods to decrease the GD relapse rate after ATD treatment.Articles published in PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, Wan Fang, and Chinese Biomedical Literature databases before January 2019 were collected. Patients newly diagnosed with GD, who were aged16 years, were treated with ATD. Follow-up was then conducted for at least 12 months after ATD withdrawal. Only prospective or retrospective studies were eligible. The primary end point was the recurrence of GD during follow-up. All the data from the trials were analyzed via meta-analysis and meta-regression. p values 0.05 were considered statistically significant, and statistical heterogeneity was assessed by using IA total of 20 studies and 3242 patients were involved in this meta-analysis, with 1681 patients relapsed (incidence rate, 51.9%) during the follow-up time. Analysis of risk factors suggested that younger age (weighted raw mean difference [RMD], -3.51; 95% CI, -5.74 to -1.29), larger thyroid volume (RMD, 4.38; 95% CI, 1.68 to 7.08), bigger goiter size (1.94% risk; 95% CI, 0.43 to 3.46), higher free triiodothyronine level (RMD, 5.09; 95% CI, 4.42 to 5.77), and higher free thyroxine level (RMD, 4.21; 95% CI, 0.54 to 7.89) were associated with the higher relapse rate of GD. The block-replace ATD regimen (a fixed high dose of an ATD with levothyroxine supplementation to maintain euthyroidism) (risk ratio, 0.64; 95% CI, 0.52 to 0.78) exhibits a lower relapse rate than the titration regimen (an ATD used alone and dose adjusted according to thyroid function tests).This analysis revealed that certain risk factors were associated with GD relapses such as younger age, larger goiter size or thyroid volume, and the higher free triiodothyronine or free thyroxine level in the diagnosing phase of GD. For patients with these clinical characteristics, early definitive treatment with radioactive iodine or surgery should be offered to those who are unlikely to achieve remission with ATDs only. In addition, more prospective cohort studies with different ATD regimens would help to determine the optimum ATD treatment for patients with GD. PROSPERO identifier: CRD 42019146825.

Previous works showed that chronic exposure to Aroclor 1254 disrupted glucose homeostasis and induced insulin resistance in male mice. To further observe the different effects of Aroclor 1254 exposure on the pancreatic α-cells and β-cells, male mice were exposed to Aroclor 1254 (0, 0.5, 5, 50, 500 μg/kg) for 60 days, the pancreas was performed a histological examination. The results showed that the percentage of apoptosis cell (indicated by TUNEL assay) was increased in both α-cells and β-cells, as the Aroclor 1254 dose was increased; the proliferation (indicated by PCNA expression) rate of β-cells was elevated while that of α-cells was not affected, resulting in an increased β-cell mass and a decreased α-cell mass in a dose-depend manner. The number of Pdx-1 positive β-cells was significantly increased whereas that of Arx positive α-cells was markedly decreased, indicating an enhanced β-cell neogenesis and a weakened α-cell neogenesis. The drastically reduction of serum testosterone levels in all the treatments suggested an anti-androgenic potency of Aroclor 1254. The up-regulation of estrogen receptors (ERα and ERβ) and androgen receptor in β-cells might be responsible for the increased β-cell mass and neogenesis.

The present study was conducted to investigate the effects and mechanisms of hypothyroidism, induced by administration of 0.2% methimazole through the food, on lipid metabolism in the liver of juvenile yellow catfish Pelteobagrus fulvidraco. To this end, yellow catfish were fed diets containing either 0 or 2g methimazole per kg of diet for 8weeks, respectively. The results showed that fish fed diet containing methimazole had a significant reduction in growth performance, plasma THs levels and hepatic lipid content. Meanwhile, methimazole treatment inhibited the activities of lipogenic enzymes (6-phosphogluconate dehydrogenase, glucose 6-phosphate dehydrogenase, malic enzyme, isocitrate dehydrogenase and fatty acid synthase) and the mRNA levels of genes involved in lipogenesis (6-phosphogluconate dehydrogenase, glucose 6-phosphate dehydrogenase, fatty acid synthase, acetyl-CoA carboxylase α, sterol-regulator element-binding protein-1 and liver X receptor), but increased lipolytic enzyme (carnitine palmitoyltransferase 1) activity and the expression of genes involved in lipolysis (carnitine palmitoyltransferase 1a, hormone-sensitive lipase and peroxisome proliferators-activated receptor α). Thus, our study indicated that dietary methimazole-induced hypothyroidism could disturb the normal processes of lipid metabolism at the enzymatic and molecular levels in yellow catfish, and the reduced hepatic lipid content by hypothyroidism was attributable to the down-regulation of lipogenesis and up-regulation of lipolysis.

Sickness behavior is an expression of a motivational state triggered by activation of the peripheral innate immune system, whereby an organism reprioritizes its functions to fight infection. The relationship between thyroid hormone and immune cells is complex, and additional insights are needed about the involvement of the cross-talk between thyroid hormone, the central nervous system and immune function, as demonstrated by the consequences to sickness behavior. The aim of this work was to evaluate sickness behavior in hypothyroid mice. Control mice and mice treated with propylthiouracil (PTU) for 30 days (0.05%; added to drinking water) received a single dose of LPS (200 μg/kg; i.p.) or saline, and the behavioral response was assessed for 24 h. We provide evidence that thyroid status acts a modulator for the development of depressive-like and exploratory behaviors in mice that are subjected to an immunological challenge because the PTU pretreatment delayed the LPS-induced behavioral changes observed in an open field test and in a forced swimming test. This response was observed concomitantly with a lower thermal index until 4 h after the LPS administration. This result demonstrates that thyroid status modifies behavioral responses to immune challenge and suggests that thyroid hormones are essential for the manifestation of sickness behavior during endotoxemia.

It has been reported that various metal coordination compounds have improved some biological properties. A high activity of acid phosphatase (AcP) is associated to several diseases (osteoporosis, Alzheimer's, prostate cancer, among others) and makes it a target for the development of new potential inhibitors. Anti-thyroid agents have disadvantageous side effects and the scarcity of medicines in this area motivated many researchers to synthesize new ones. Several copper(II) complexes have shown antifungal activities. In this work we presented for a first time the inhibition of AcP and the anti-thyroid activity produced by methimazole-Cu(II) complexes. Cu-Met ([Cu(MeimzH)2(H2O)2](NO3)2·H2O) produces a weak inhibition action while Cu-Met-phen ([Cu(MeimzH)2(phen)(H2O)2]Cl2) shows a strong inhibition effect (IC50 = 300 μM) being more effective than the reported behavior of vanadium complexes. Cu-Met-phen also presented a fairly good anti-thyroid activity with a formation constant value, Kc = 1.02 × 1010 M-1 being 106 times more active than methimazole (Kc = 4.16 × 104 M-1) in opposition to Cu-Met which presented activity (Kc = 9.54 × 103 M-1) but in a lesser extent than that of the free ligand. None of the complexes show antifungal activity except Cu-phen (MIC = 11.71 μg mL-1 on Candida albicans) which was tested for comparison. Besides, albumin interaction experiments denoted high affinity toward the complexes and the calculated binding constants indicate reversible binding to the protein. Fil: Urquiza, Nora María. Universidad Nacional de Tucumán; Argentina Fil: Islas, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Ariza, Santiago T.. Universidad Nacional de La Plata; Argentina Fil: Jori, Nadir. Universidad Nacional de La Plata; Argentina Fil: Martínez Medina, Juan José. Universidad Nacional del Chaco Austral; Argentina Fil: Lavecchia, Martín José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: López Tévez, Libertad Leonor. Universidad Nacional del Chaco Austral; Argentina Fil: Lezama, Luis. Universidad del País Vasco; España Fil: Rojo, Teófilo. Universidad del País Vasco; España Fil: Williams, Patricia Ana María. Universidad Nacional de La Plata; Argentina Fil: Ferrer, Evelina Gloria. Universidad Nacional de La Plata; Argentina

Background and aims Despite strong mechanistic data, and promising results from in vitro and animal studies, the ability of probiotic bacteria to improve blood pressure and serum lipid concentrations in humans remains uncertain. The aim of this study was to determine the effect of Lactobacillus acidophilus La5 and Bifidobacterium animalis subsp lactis Bb12, provided in either yoghurt or capsule form, on home blood pressure and serum lipid profile. Methods and results Following a 3-week washout period, 156 overweight men and women over 55 y were randomized to a 6-week double-blinded, factorial, parallel study. The four intervention groups were: A) probiotic yoghurt plus probiotic capsules; B) probiotic yoghurt plus placebo capsules; C) control milk plus probiotic capsules; and D) control milk plus placebo capsules. Each probiotic test article provided a minimum L . acidophilus La5 and B . animalis subsp. lactis Bb12 dose of 3.0 × 10 9 CFU/d. Home blood pressure monitoring, consisting of 7-day bi-daily repeat measurements, were collected at baseline and week 6. Fasting total cholesterol, low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), and serum triglyceride were performed at baseline and week 6. When compared to control milk, probiotic yoghurt did not significantly alter blood pressure, heart rate or serum lipid concentrations ( P > 0.05). Similarly, when compared to placebo capsules, supplementation with probiotic capsules did not alter blood pressure or concentrations of total cholesterol LDLC, HDLC, or triglycerides ( P > 0.05). Conclusions The probiotic strains L . acidophilus La5 and B . animalis subsp. lactis Bb12 did not improve cardiovascular risk factors.

Amiodarone is a widely used anti-arrhythmic drug. A common long-term complication is amiodarone-induced thyrotoxicosis (AIT). We examined retrospectively the efficacy of anti-thyroid drugs with or without prednisolone and the role of surgical thyroidectomy in the treatment of AIT in a single centre, in an iodine-replete region of Australia.A retrospective audit of patients with AIT was performed between 2002-2012 at this centre. Twenty-seven patients, mean age 60.9 ± 2.3 years were identified. Medical therapy (anti-thyroid drugs, prednisolone) was commenced according to the treating endocrinologist. The main outcomes were time to euthyroidism and number proceeding to thyroidectomy.Of 11 patients commenced on anti-thyroid drugs alone, seven (64%) required the addition of prednisolone. Baseline free T4 was significantly higher in those ultimately treated with prednisolone (58.4 ± 6.3pmol/L) versus those not (31.7 ± 3.4pmol/L, P0.05). Although similar results were seen with free T3, the difference was not significant (P=0.06). In patients with baseline free T430pmol/L, 75% (3/4) achieved euthyroidism without prednisolone. Neither the use of prednisolone nor continuation of amiodarone significantly influenced time to euthyroidism. Eleven patients (41%) proceeded to surgical thyroidectomy, which was undertaken by an experienced surgical team without significant complications and no mortality.Patients with AIT generally required glucocorticoids. Mild disease (free T430pmol/L) may be successfully treated with anti-thyroid drugs alone. Surgical thyroidectomy is a safe and effective treatment for those refractive to medical therapy.

Graves' disease is an autoimmune disorder resulting from thyrotropin receptor stimulation by autoantibodies. It may occur at any age during childhood, but its frequency increases with age, peaking during adolescence. Symptoms and signs are often recognizable and proportional to the increase in serum free thyroid hormone levels. Antithyroid drug treatment with methimazole (or carbimazole) is recommended for initial treatment, but relapse rates are high, with remission achieved in only 30% of children after a first course of treatment for about two years. More prolonged medical treatment may increase the remission rate to up to 50%. Alternative treatments, such as radioactive iodine or thyroidectomy, are considered in cases of relapse, lack of compliance or antithyroid drug toxicity. Relapse risk decreases with increasing duration of the first course of antithyroid drug treatment. The identification of other predictive factors, such as severe biochemical hyperthyroidism at diagnosis, young age and the absence of other autoimmune conditions, has made it possible to stratify patients according to the risk of relapse, leading to improvements in patient management, by facilitating the identification of patients requiring long-term antithyroid drug treatment or early alternative therapy.

Syncope is a common emergency department (ED) chief complaint, with many known but also unknown causes. Here we present a novel ED presentation of a young woman with new-onset hyperthyroidism that masqueraded as a syncopal event with head trauma. A 21-year-old woman arrived in the ED with head trauma as the result of seemingly unprovoked syncope, due to her history as well as the nature of her trauma. Persistent tachycardia during her ED course after an unremarkable full trauma evaluation prompted ordering of additional lab testing, which revealed evidence of thyrotoxicosis. Here we consider the possibility of thyroid dysfunction resulting in syncope.

In this paper, Au–Ag–Au double shell nanoparticles were prepared based on the reduction of the metal salts HAuCl4 and AgNO3 at the surface of seed particles. Due to the synergistic effect between Au and Ag, the hybrid nanoparticles are particularly stable and show excellent performances on the detection of 2-mercapto-1-methylimidazole (methimazole). The binding of target molecule at the surface of Au–Ag–Au double shell nanoparticles was demonstrated based on both localized surface plasmon resonance (LSPR) and surface-enhanced Raman scattering (SERS) spectra. The LSPR intensity is directly proportional to the methimazole concentration in the range of 0.10–3.00×10−7 mol L−1. The SERS spectrum can be applied in identification of methimazole molecule. The LSPR coupled with SERS based on the Au–Ag–Au double shell nanoparticles would be very attractive for the quantitative determination and qualitative analysis of the analytes in medicines.

We present a case of a patient with thyroid storm exhibiting symptoms similar to those of traumatic injury. This patient presented multiple traumatic wounds on his limbs and face, loss of consciousness, and tachycardia. Diagnosis was initially confounded by the similarity between the symptoms of traumatic hypovolemic shock and trauma-induced thyroid storm. This case report discusses the factors leading to the diagnostic delay and highlights the dangerous manifestations of thyroid storm.