Increased Thyroid Hormone Levels Research Articles

Thyroid and neurobehavioral effects of DiNP on GH3 cells and larval zebrafish (Danio rerio)

Diisononyl phthalate (DiNP) has been used to replace bis(2-ethylhexyl) phthalate (DEHP) and is frequently found in the environment and humans. DiNP is reported for its anti-androgenic activity; however, little is known about its effects on thyroid function and neurodevelopment. In the present study, the thyroid disruption and neurobehavioral alteration potential of DiNP and its major metabolites were assessed in a rat pituitary carcinoma cell line (GH3) and embryo-larval zebrafish (Danio rerio). In GH3 cells, exposure to DiNP and its metabolites not only resulted in increased proliferation but also induced transcriptional changes in several target genes, which were different from those observed with DEHP exposure. In larval fish, a 5-day exposure to DiNP caused significant increases in thyroid hormone levels, following a similar pattern to that reported for DEHP exposure. Following exposure to DiNP, the activity of the larval fish decreased, and neurodevelopment-related genes, such as c-fos, elavl3, and mbp, were down-regulated. These changes are generally similar to those observed for DEHP. Up-regulation of elavl3 and down-regulation of gap43 gene, which are important for both thyroid hormone production and neurodevelopment, respectively, support the potential for both thyroid and behavioral disruption of DiNP. Overall, these results emphasize the need to consider the adverse thyroid and neurodevelopmental effects in developing regulations for DEHP-replacing phthalates.

Urinary proteomics for noninvasive monitoring of biomarkers of chronic mountain sickness in a young adult population using data-independent acquisition (DIA)-based mass spectrometry

Different populations exhibit varying pathophysiological responses to plateau environments. Therefore, it is crucial to identify molecular markers in body fluids with high specificity and sensitivity to aid in determination. Proteomics offers a fresh perspective for investigating protein changes linked to diseases. We utilize urine as a specific biomarker for early chronic mountain sickness (CMS) detection, as it is a simple-to-collect biological fluid. We collected urine samples from three groups: plains health, plateau health and CMS. Using DIA's proteomic approach, we found differentially expressed proteins between these groups, which will be used as a basis for future studies to identify protein markers. Compared with the healthy plain population, 660 altering proteins were identified in plateau health, which performed the resistance to altitude response function by boosting substance metabolism and reducing immune stress function. Compared to the healthy plateau population, the CMS group had 140 different proteins identified, out of which 8 were potential biomarkers for CMS. Our study has suggested that CMS may be closely related to increased thyroid hormone levels, oxidative damage to the mitochondria, impaired cell detoxification function and inhibited hydrolase activity. SignificanceOur team has compiled a comprehensive dataset of urine proteomics for AMS disease. We successfully identified differentially expressed proteins between healthy and AMS groups using the DIA proteomic approach. We discovered that 660 proteins were altered in plateau health compared to the healthy plain population, resulting in a heightened resistance to altitude response function by boosting substance metabolism and reducing immune stress function. Additionally, we pinpointed 140 different proteins in the AMS group compared to the healthy plateau population, with 8 showing potential as biomarkers for AMS. Our findings suggest that the onset of AMS may be closely linked to increased thyroid hormone levels, oxidative damage to the mitochondria, impaired cell detoxification function and inhibited hydrolase activity.

Thyroid gland dysfunction in heart rhythm disorders

Thyroid gland dysfunction is estimated to occur in approximately 5% of the population and affects people of different ages. Cardiovascular diseases can occur in diseases such as hyperthyroidism as well as hypothyroidism. Increased thyroid hormone levels precipitate sympathetic nervous system activation, potentially culminating in heightened heart rate (tachycardia) and disruptions in electrical conduction. This influence can induce QT interval shortening and provoke premature ventricular contractions (PVCs), amplifying the propensity for more severe arrhythmic manifestations. Insufficiency of thyroid hormones decelerates metabolic activity, potentially leading to bradycardia. Hypothyroidism elevates the risk of atrial fibrillation occurrence and additionally elongates QT intervals, enhancing the susceptibility to torsade de pointes. Untreated hormone disorders affect severe cardiac complications, which can occur in patients with previously diagnosed heart disease. Effective management of cardiac arrhythmias in patients with thyroid dysfunction necessitates interdisciplinary collaboration between endocrinologists and cardiologists.

Effect of perinatal exposure to glyphosate and its mixture with 2,4-D and dicamba on rat dam kidney and thyroid function and offspring's health

The increasing use of the herbicide mixture of glyphosate, dicamba and 2-4-D to deal with glyphosate-resistant weeds raises concerns regarding human health and environmental risks. This study aimed to evaluate the effects of developmental exposure to glyphosate and a herbicide mixture containing glyphosate, dicamba and 2-4-D on rat dams' kidney and thyroid function and offspring's health. Pregnant Wistar rats were exposed from day-6 of gestation till weaning to regulatory relevant doses of glyphosate corresponding to the European Union (EU) acceptable daily intake (ADI; 0.5 mg/kg bw/day), and the no-observed-adverse-effect level (NOAEL; 50 mg/kg bw/day), and to a mixture of glyphosate, dicamba and 2,4-D all at the EU ADI (0.5, 0.002 and 0.3 mg/kg bw/day) respectively. After weaning the dams were sacrificed and blood and organs were collected. The pups' health was assessed by measuring viability, gestational and anogenital indices. Perinatal exposure to GLY alone and the herbicide mixture resulted in anti-androgenic effects in male offspring. In dams, exposure to glyphosate resulted in kidney glomerular and tubular dysfunction as well as increased thyroid hormone levels in a dose-dependent manner. Furthermore, exposure to the herbicide mixture resulted in effects similar to those observed with glyphosate at the NOAEL, suggesting at least an additive effect of the herbicide mixture at doses individually considered safe for humans.

Thyroid Hormone Resistance Syndrome in an Adolescent Girl: A Case Report

Introduction: Resistance to Thyroid Hormones (RTH) is a rare, hereditary disease characterized by diminished sensitivity of target tissues to thyroid hormones. Most cases (~85%) are caused by mutations in the thyroid hormone receptor beta (THRβ) gene (RTHβ). The clinical spectrum of RTHβ is quite broad and highly heterogeneous, and the hallmark of the condition is a paucity of signs and symptoms of thyroid dysfunction despite elevated levels of T4 and T3, with a concomitant non-suppressed TSH. Case Report: Here, we describe a rare case of RTHβ in a female adolescent who was initially misdiagnosed and treated for Graves’ disease, but whose unusual evolution motivated her transference to a tertiary center. The patient exhibited mild manifestations, presenting with a goiter without compressive symptoms and some degree of cognitive impairment with learning disability. Misdiagnosis of RTHβ as Graves’ disease can lead to unnecessary treatments such as anti-thyroid medication, thyroidectomy or radioiodine, but treatment is generally not necessary for most patients with RTHβ. Discussion and Conclusion: Establishing the diagnosis of RTHβ can be challenging. It must be considered in patients who present with a goiter and increased thyroid hormone levels with an unsuppressed TSH, to potentially avoid an incorrect diagnosis of primary hyperthyroidism and the implementation of unnecessary and harmful treatments. Most patients with RTHβ are asymptomatic, and in children, particular attention must be paid to growth, bone maturation, and mental development.

Correlation between latent toxoplasmosis and thyroid hormone levels in sera of schizophrenic patients

Latent toxoplasmosis is a prevalent chronic infection caused by a protozoan parasite called Toxoplasma gondii. Recent studies have shown that T. gondii may affect thyroid hormone levels and thus induce behavioral alteration. However, this correlation has been inadequately investigated. Therefore, we aimed to examine the relationship between latent toxoplasmosis and thyroid hormone levels in schizophrenic patients. For this purpose, blood samples and sociodemographic information were collected from 101 schizophrenic patients attending three psychiatric hospitals in Kurdistan region of Iraq. Anti-T. gondii-IgG antibodies and thyroid hormones levels (TSH, T3, T4) were determined in sera of all patients using ELISA technique. Anti-T. gondii-IgG antibodies were detected in sera of 40 (39.6%) out of 101 schizophrenic patients. Logistic regression analysis showed significant association between toxoplasmosis and schizophrenic patients in 50-60 age group (OR=6.177, p=0.05), and un-employed patients (OR=3.562, p=0.05). Data analysis showed non-significant difference in TSH levels between IgG seropositive and IgG seronegative group (p>0.05). On the other hand, T4 levels were significantly higher in the seropositive (10.16 ± 2.61) than seronegative group (7.01 ± 2.01), with highly significant positive correlation between IgG and T4 levels (p= 0.001). Finally, T3 levels were significantly higher in the seropositive (1.91 ± 0.5) than seronegative group (1.12 ± 0.43), with non-significant positive correlation between IgG and T3 levels (p=0.30). Owing to the fact that there was statistically significant increase in thyroid hormone levels in T. gondii seropositive patients, our results suggest that there is a significant association between toxoplasmosis and thyroid hormone levels in schizophrenic patients.

Effect of Lugol's solution on 131I therapy efficacy in Graves' disease.

Lugol's solution could control thyroid function and suppress 131I uptake in hyperthyroidism. This study aimed to investigate the appropriate time to withdraw Lugol's solution before 131I therapy (RIT) in Graves' disease (GD) patients, and how this should influence 131I uptake and RIT outcome. Two groups (125 cases and 1805 cases) of GD patients received RIT, who were pre-treated with and without Lugol's solution (RI-CI group and RI group). The RI-CI group was further divided into the following sub-groups depending on the duration span between Lugol's solution withdrawal and RIT: sub-group A, 4-7 d (n = 49); sub-group B, 8-14 d (n = 41); and sub-group C, 15-30 d (n = 35). The highest radioactive iodine uptake rate (RAIUmax), effective half-life (Teff), TRAb, and free triiodothyronine (FT3) and free thyroxine (FT4) levels were compared, and therapeutic outcome was evaluated. There were no significant differences in RAIUmax, TRAb, and Teff among the four sub-groups (P > 0.05). Both FT3 and FT4 levels in sub-groups A and B were lower than those in group RI and sub-group C (P < 0.05). The outcome of non-hyperthyroidism (euthyroidism + hypothyroidism) in groups RI-CI and RI was significantly different at post-RIT month 1 and 3 (P < 0.05). However, intergroup differences at 6 and 12months were not significant (P > 0.05). Withdrawal of Lugol's solution 4-7 or 8-14 d before RIT does not influence 131I uptake and RIT efficacy in GD. Moreover, in order to avoid a rapid increase in thyroid hormone levels at the same time, Lugol's solution should be withdrawn 4-7 d before RIT.

ASSOCIATION OF THYROID HORMONE LEVELS WITH LUTEAL PHASE DEFICIENCY IN INFERTILE WOMEN

Objectives: To find out the association of thyroid hormone levels with Luteal Phase Deficiency (LPD) Methodology: This prospective study was conducted at Peshawar Medical College, from April to August 2013. The sample size was 125 infertile women of the reproductive age group (18-42 years) selected through consecutive sampling technique. On the 22nd and 23rd of the menstrual cycle, endometrial biopsies were performed. Chemilu­minescence Immunoassay was used to estimate the serum levels of the thyroid hormones. SPSS version 19 was used to conduct the statistical analysis. The Chi-square test was used to see whether there was any statistically significant difference between the endometrial findings of patients with normal thyroid profiles and those who had elevated thyroid hormone levels. It was deemed statistically significant when the probability value was p&lt;0.05. Results: The majority of infertile patients (n=99) had normal thyroid profiles, followed by hyperthyroid cases (n=23). Only three turned out to be hypothyroid. There was no significant difference in endometrium between the patients with normal and increased thyroid hormone levels. Conclusion: Although no statistically significant association between the thyroid hormones levels and the endo­metrium in cases of Luteal Phase Deficiency could be found in this study, their role cannot be ignored and needs further evaluation

Differential Diagnosis of Thyrotoxicosis by Machine Learning Models with Laboratory Findings.

Differential diagnosis of thyrotoxicosis is essential because therapeutic approaches differ based on disease etiology. We aimed to perform differential diagnosis of thyrotoxicosis using machine learning algorithms with initial laboratory findings. This is a retrospective study through medical records. Patients who visited a single hospital for thyrotoxicosis from June 2016 to December 2021 were enrolled. In total, 230 subjects were analyzed: 124 (52.6%) patients had Graves’ disease, 65 (28.3%) suffered from painless thyroiditis, and 41 (17.8%) were diagnosed with subacute thyroiditis. In consideration that results for the thyroid autoantibody test cannot be immediately confirmed, two different models were devised: Model 1 included triiodothyronine (T3), free thyroxine (FT4), T3 to FT4 ratio, erythrocyte sediment rate, and C-reactive protein (CRP); and Model 2 included all Model 1 variables as well as thyroid autoantibody test results, including thyrotropin binding inhibitory immunoglobulin (TBII), thyroid-stimulating immunoglobulin, anti-thyroid peroxidase antibody, and anti-thyroglobulin antibody (TgAb). Differential diagnosis accuracy was calculated using seven machine learning algorithms. In the initial blood test, Graves’ disease was characterized by increased thyroid hormone levels and subacute thyroiditis showing elevated inflammatory markers. The diagnostic accuracy of Model 1 was 65–70%, and Model 2 accuracy was 78–90%. The random forest model had the highest classification accuracy. The significant variables were CRP and T3 in Model 1 and TBII, CRP, and TgAb in Model 2. We suggest monitoring the initial T3 and CRP levels with subsequent confirmation of TBII and TgAb in the differential diagnosis of thyrotoxicosis.

The Effect of Irisin on Thyroid Hormone Levels in Chronic Paroxetine-Treated Rats.

It is known that serotonin reuptake inhibitors (SSRIs), which are widely used in mood disorders, affect the hypothalamic-pituitary-thyroid axis activity. In this study, we investigated the effect of paroxetine, an SSRI, on thyroid hormone levels in rats. We also examined the role of irisin, a newly discovered potential regulatory hormone for metabolism, on paroxetine-induced changes. A total of 64 Sprague-Dawley female and male rats were randomly divided into four subgroups for each gender and treated as follows: sham-operated control (vehicle), paroxetine (treated with 20mg/kg paroxetine by oral gavage), irisin (100ng/kg/day for 28days with mini-osmotic pumps), and paroxetine + irisin group (n = 8). Serum fasting free triiodothyronine (fT3) and free thyroxine (fT4) levels were measured by automated chemiluminescence method. Serum thyroid-stimulating hormone (TSH) level was determined with enzyme-linked immunosorbent analysis (ELISA). Compared to the sham control group (p < 0.05), the significantly reduced fT4 and TSH serum levels in paroxetine-treated male animals were markedly increased by subcutaneous irisin perfusion. fT3 levels significantly increased in both irisin (4.35 ± 0.17 pq/mL) and paroxetine + irisin groups (4.51 ± 0.19 pq/mL) compared to sham control (3.60 ± 0.23 pq/mL) and paroxetine groups (3.57 ± 0.12 pq/mL) (p < 0.05). It was observed that serum fT3, fT4, and TSH levels decreased in female animals receiving paroxetine compared to the sham control group. Subcutaneous administration of irisin increased these hormone levels. However, these changes were not statistically significant. These results suggested that irisin may play a role in the mechanism underlying the beneficial effects of exercise in preventing SSRI-related side effects by increasing thyroid hormone levels, which were decreased by paroxetine.

Increased Thyroid Hormone Levels in Pesticide Sprayer at Agricultural Area

Pesticides still used massively in the agricultural sector would cause many poisoning and serious health problems. Organophosphate pesticides have been identified as endocrine-disrupting chemicals. This study aimed to analyze the comparison of thyroid hormone levels between the sprayers chronically exposed to pesticides and the control respondents who had never been exposed to pesticides. This study was an analytical observational with a cross-sectional design. The total number of respondents was 150, 50 as sprayers and 100 as control respondents. The venous blood samples were examined using the Enzyme-Linked Immunosorbent Assay (ELISA). The findings significantly showed that the sprayer had a higher level of thyroid-stimulating hormone (TSH) (4.776 ± 1.1166), lower triiodothyronine (T3) (108.822 ± 18.810), and lower thyroxine (T4) (7.808 ± 1.067). Determinant factors among sprayers that significantly correlated to TSH levels was (age = 0.006; work duration = 0.000; PPE = 0.045; body position = 0.014; type of pesticides = 0.004), correlated with T3 levels was (age = 0.037; body position = 0.045), correlated with T4 levels was (age = 0.000; PPE = 0.045). It could be concluded that chronic organophosphate exposure would increase TSH and decrease T3 and T4.

An Erythropoietin-Independent Mechanism of Erythrocytic Precursor Proliferation Underlies Hypoxia Tolerance in Sea Nomads.

The Bajau Sea Nomads were recently demonstrated to have evolved larger spleens as an adaptation to millennia of a marine foraging lifestyle. The large-spleen phenotype appears to derive from increases in thyroid hormone (TH) production as a result of reduced expression of phosphodiesterase 10A (PDE10A), though the exact mechanism remains unknown. Through pharmacological inhibition of PDE10A using the selective inhibitor MP-10 in mice, we were able to mimic the Bajau adaptation and show that treated mice had significantly larger spleens than control animals. This difference appears connected to an excess of early stage erythrocytes and an apparent increase in red blood cell (RBC) precursor proliferation in response to increased TH. However, we determined that the stimulation of RBC production in the mouse model via TH is Erythropoietin (EPO)-independent, unlike in the altitude (chronic hypoxemia) response. We confirmed this using human GWAS data; although the Bajau PDE10A variants are significantly associated with increased TH levels and RBC count, they are not associated with EPO levels, nor are other strongly thyroid-associated SNPs. We therefore suggest that an EPO-independent mechanism of stimulating RBC precursor proliferation via TH upregulation underlies the increase in spleen size observed in Sea Nomad populations.

An Early Wave of Macrophage Infiltration Intertwined with Antigen-Specific Proinflammatory T Cells and Browning of Adipose Tissue Characterizes the Onset of Orbital Inflammation in a Mouse Model of Graves' Orbitopathy.

Background: Graves' orbitopathy (GO) is an autoimmune-driven manifestation of Graves' disease (GD) where pathogenic autoantibodies to the thyrotropin receptor (TSHR) activate orbital fibroblasts/preadipocytes in the orbital tissue to induce inflammation and extracellular matrix deposition. Since there are significant limitations to study immunological and proinflammatory mediator expression in early and during disease progression in GO patients, we used our experimental mouse model to elucidate early pathogenic processes. Methods: We have developed a robust mouse model of GD/GO induced by electroporation immunization of plasmid encoding human TSHR A-subunit, comprising multiple injections over a course of 15 weeks to fully recapitulate the orbital pathology. In this study, we investigated kinetics of GO development in the model by serial analyses of immunological and cellular parameters during course of orbital inflammation. Results: Pathogenic anti-TSHR antibodies with thyroid-stimulating properties developed early after the second immunization step with concomitant induction of hyperthyroidism. Examination of orbital tissue showed an early wave of macrophage infiltration followed subsequently by CD3+ T cells into the orbital tissue. Examination of antigen-specific T cell activity using recombinant human A-subunit protein showed high CD8+ T cell proliferation during this early phase of disease onset, whereas effector CD4+ T cells and CD25+FOXP3+ regulatory T cells (Tregs) were downregulated. The early phase of disease was also characterized by abundant presence of proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Moreover, as the disease progressed, there was significant increase in browning of orbital fat tissue, which may be dependent on the proinflammatory milieu and/or the increased thyroid hormone levels during the established hyperthyroid status. Conclusions: This work revealed early infiltration of macrophages in the orbital region and induction of pathogenic anti-TSHR antibodies during disease onset in the model. This was followed subsequently by influx of CD8+ T cells specific for TSHR coupled with reduction in Tregs and substantial increase in brown adipose tissue. These new insights into the development of orbital inflammation in the model have implications for testing new therapeutic regimens by targeting macrophage function during early phases of orbital inflammation in the model.

MicroRNA-577 aggravates bone loss and bone remodeling by targeting thyroid stimulating hormone receptor in hyperthyroid-associated osteoporosis.

Traditionally, hyperthyroid-associated osteoporosis has been considered to be the result of increased thyroid hormone levels. The pathogenesis of hyperthyroid-associated osteoporosis remains unclear. Thyroid stimulating hormone receptor (TSHR) is closely associated with osteoporosis. Our study aimed to explore the role of TSHR and its upstream microRNA (miRNA) in hyperthyroid-associated osteoporosis. Bioinformatics analysis (starBase and Targetscan) and a wide range of experiments including reverse-transcription quantitative polymerase chain reaction, luciferase reporter, western blot analysis of osteogenic differentiation markers including OSX, OCN, ALP, OPN, and COL1, hematoxylin and eosin staining, Alizarin Red staining assays were used to explore the function and mechanism of TSHR in hyperthyroid-associated osteoporosis. First, we observed that TSHR was downregulated in bone marrow mesenchymal stem cells (BMSCs) isolated from rats after culture in osteogenic medium for 7 days. Functionally, overexpression of TSHR accelerates BMSC osteogenic differentiation. Mechanistically, we predicted four potential miRNAs for TSHR. MiR-577 was validated to bind with TSHR. Rescue assays showed that miR-577 overexpression inhibited BMSC osteogenic differentiation via targeting TSHR. In vivo experiments showed that miR-577 aggravated bone loss and bone remodeling and our data showed that it is achieved by targeting TSHR in hyperthyroid-associated osteoporosis. This finding may deep our understanding of the pathogenesis of hyperthyroid-associated osteoporosis.

A Longitudinal Study of Medial Temporal Lobe Volumes in Graves Disease.

Context Neuropsychiatric symptoms are common features of Graves disease (GD) in hyperthyroidism and after treatment. The mechanism behind these symptoms is unknown, but reduced hippocampal volumes have been observed in association with increased thyroid hormone levels.ObjectiveThis work aimed at investigating GD influence on regional medial temporal lobe (MTL) volumes.MethodsSixty-two women with newly diagnosed GD underwent assessment including magnetic resonance (MR) imaging in hyperthyroidism and 48 of them were followed up after a mean of 16.4 ± 4.2 SD months of treatment. Matched thyroid-healthy controls were also assessed twice at a 15-month interval. MR images were automatically segmented using multiatlas propagation with enhanced registration. Regional medial temporal lobe (MTL) volumes for amygdalae and hippocampi were compared with clinical data and data from symptom questionnaires and neuropsychological tests.ResultsPatients had smaller MTL regions than controls at inclusion. At follow-up, all 4 MTL regions had increased volumes and only the volume of the left amygdala remained reduced compared to controls. There were significant correlations between the level of thyrotropin receptor antibodies (TRAb) and MTL volumes at inclusion and also between the longitudinal difference in the levels of free 3,5,3′-triiodothyronine and TRAb and the difference in MTL volumes. There were no significant correlations between symptoms or test scores and any of the 4 MTL volumes.ConclusionDynamic alterations in the amygdalae and hippocampi in GD reflect a previously unknown level of brain involvement both in the hyperthyroid state of the condition and after treatment. The clinical significance, as well as the mechanisms behind these novel findings, warrant further study of the neurological consequences of GD.

Successful Management of Hyperthyroidism With Lithium and Radioiodine in a Patient With Previous Methimazole-Induced Agranulocytosis

Introduction: Antithyroid drug (ATD) therapy is the first-line treatment of Graves’ hyperthyroidism. Agranulocytosis, although rare, is a life-threatening condition associated with ATD therapy. For patients who recovered from ATD-induced agranulocytosis, surgery or radioiodine (RAI) therapy are adequate options to restore the patient’s euthyroid state. Here we report a case of ATD-related agranulocytosis where lithium therapy was used before RAI to control thyrotoxicosis and prevent worsening of hyperthyroidism. Case Report: A 74-year-old female with a previous history of hypertension presented with a 2-month history of weight loss (12 lbs), palpitations and shortness of breath. She was afebrile with a heart rate of 110, a blood pressure of 149/80, a fine tremor and a moderate diffuse goiter. She had a normal eye exam. Laboratory evaluation demonstrated TSH <0.01 uIU/mL (0.35-5.5), FT4 3.11 ng/dL (0.51-1.65) and TSH receptor antibody (TRAb) 40 (<1,0 U/L), consistent with thyrotoxicosis due to Graves’ disease. She was started on methimazole (MMI) 15mg and metoprolol. After four weeks, symptoms resolved and thyroid function tests (TFT) improved. However, after two months of treatment, she was hospitalized for fever, diarrhea and abdominal pain. White blood cell count (WBC) was 650/μL, and neutrophil count was 90/μL. A diagnosis of gastroenteritis and agranulocytosis was made and MMI was stopped. After seven days, symptoms resolved, the neutrophil count was 2200/ul and TFT were acceptable (FT4 1.25, ng/dL TT3 1.67 ng/ml, TSH < 0.02 uIU/mL). She was discharged without ATDs and a RAI dose of 20 mCi was scheduled. However, RAI therapy had to be postponed due to COVID-19 pandemic restrictions. After 3 weeks, TFT worsened and therapy with lithium carbonate 300 mg TID was started as the patient refused thyroidectomy. Lithium was initiated 12 days before RAI therapy and was maintained 7 days after the procedure. No side effects associated with lithium treatment were reported. TFT 7 days after RAI were FT4 1.43, ng/dL TT3 2.05 ng/ml and TSH < 0.02 uIU/mL. One month later, the patient was euthyroid without need for thyroid medication and remains on follow up. Discussion: Serum thyroid hormone (TH) concentrations usually increase after RAI therapy for Graves’ disease, a worrisome fact in patients with increased risk for cardiovascular complications. Previous studies report that pre-RAI treatment with lithium prevents changes in serum TH concentrations and enhances RAI therapy’s effectiveness. Here, treatment with lithium was used to control thyrotoxicosis and prevent further increase in TH levels associated with RAI therapy. Lithium is particularly suitable for patients with ATD-related side effects before definitive therapy (radioiodine or thyroidectomy). The antithyroid effect of lithium in this setting should be further studied.

Toxicity and accumulation of 6-OH-BDE-47 and newly synthesized 6,6′-diOH-BDE-47 in early life-stages of Zebrafish (Danio rerio)

Dihydroxylated polybrominated diphenyl ethers (diOH-PBDEs) appear to be natural products or metabolites of PBDEs in some marine organisms, yet its toxicity is still largely unknown. With a newly lab-synthesized diOH-PBDE, 6,6′-dihydroxy-2,2′,4′4′-tetrabromodiphenyl ether (6,6′-diOH-BDE-47) in hand, the present study has provided the first data set to compare 6-hydroxy-2,2′,4′4′- tetrabromodiphenyl ether (6-OH-BDE-47) and 6,6′-diOH-BDE-47 for their acute toxicity and accumulation, and thyroid hormone levels in treated zebrafish larvae. By real time-PCR technique, transcripts of hypothalamic-pituitary-thyroid axis associated genes were also investigated in developing larvae at 96 h post fertilization (96 hpf). Apparently, 6,6′-diOH-BDE-47 was less toxic than that of 6-OH-BDE-47: 1) the 96-h LC50 (96-h median lethal concentration) of 6-OH-BDE-47 and 6,6′-diOH-BDE-47 were 235 nM and 516 nM, respectively; 2) although severe developmental delays and morphological deformities were observed in zebrafish larvae in high exposure doses, at the exposure concentration of 1–50 nM, the accumulated 6-OH-BDE-47 and 6,6′-diOH-BDE-47 is ranged between 226–2279 nmol/g and 123–539 nmol/g in treated larvae; and 3) for 6-OH-BDE-47, its bioconcentration factor (BCF) were 1.83- to 4.30-fold more than that of 6,6′-diOH-BDE-47, suggesting that the lower internal exposure concentration of 6,6′-diOH-BDE-47 may lead to lower toxicity. The increased thyroid hormone levels were recorded for 1 nM of 6-OH-BDE-47 and 20 nM of 6,6′-diOH-BDE-47, and the exposures both significantly increased thyroid gland-specific transcription of thyroglobulin gene, indicating an adverse effect associated with the HPT axis. Therefore, 6,6′-diOH-BDE-47, with lower toxicity compared to that of 6-OH-BDE-47, still possesses hazards and environmental risk.

Ameliorative effect of Aloe gel against L-T4-induced hyperthyroidism via suppression of thyrotropin receptors, inflammation and oxidative stress.

Untreated hyperthyroidism may develop serious complications. This attempt was made to investigate the potential of Aloe vera gel in regulating experimentally induced hyperthyroidism in rats. Female Wistar rats were made hyperthyroid with L-thyroxine (L-T4) at 0.5mg/kg/day, i.p. for 14days and the effects of Aloe vera methanolic fraction (AVMF) (50 or 500mg/kg/day, p.o.,) and a conventional antithyroid drug propylthiouracil (PTU) (10mg/kg, i.p.) for 30days were studied in those hyperthyroid rats. At the end, alterations in serum thyroid hormones and thyroid stimulating hormone (TSH); hepatic 5'mono-deiodinase-1(5'D1) activity, oxidative stress markers and antioxidants; serum inflammatory cytokines and the expression of thyrotropin receptor in thyroid gland were evaluated in all experimental animals. Hyperthyroid condition was confirmed by an increase in thyroid hormone levels and hepatic 5'D-1 activity with a decrease in TSH. However, either AVMF or PTU treatment in hyperthyroid rats decreased the levels of thyroid hormones and 5'D1 activity. AVMF administration in T4-induced rats also decreased the oxidative stress markers such as thiobarbituric acid reactive substances and lipid hydroperoxides and increased the antioxidant levels in liver tissues. Levels of liver marker enzymes, cytokines and different lipids were decreased in T4-induced AVMF treated rats. Further, a down regulation in the TSHR expression in thyroid was observed in AVMF or PTU treated groups. All these thyroid inhibiting effects were supported by an improvement in thyroid histology in hyperthyroid rats. It appears, about 15 compounds, as evidenced byLC-MS/MS study, mostly phenolics are involved in this anti-thyroid effects of the test compound.

Unique and overlapping effects of triiodothyronine (T3) and thyroxine (T4) on sensory innervation of the chick cornea

Multiple aspects of cornea development, including the innervation of the cornea by trigeminal axons, are sensitive to embryonic levels of thyroid hormone (TH). Although previous work showed that increased TH levels could enhance the rate of axonal extension within the cornea in a thyroxine (T4)-dependent manner, details underlying the stimulatory effect of TH on cornea innervation are unclear. Here, by examining the effects throughout all stages of cornea innervation of the two main THs, triiodothyronine (T3) and T4, we provide a more complete characterization of the stimulatory effects of TH on corneal nerves and begin to unravel the underlying molecular mechanisms. During development, trigeminal axons are initially repelled at the corneal periphery and encircle the cornea in a pericorneal nerve ring prior to advancing into the corneal stroma radially from all along the nerve ring. Overall, exogenous T3 led to pleiotropic effects throughout all stages of cornea innervation, whereas the effects of exogenous T4 was confined to timepoints following completion of the nerve ring. Specifically, exogenous T3 accelerated the formation of the pericorneal nerve ring. By utilizing in vitro neuronal explants studies we demonstrated that T3 acts as a trophic factor to directly stimulate trigeminal nerve growth. Further, exogenous T3 caused disorganized and precocious innervation of the cornea, accompanied by the downregulation of inhibitory Robo receptors that normally act to regulate the timing of nerve advancement into the Slit-expressing corneal tissues. Following nerve ring completion, the growth rate and branching behavior of nerves as they advanced into and through the cornea were found to be stimulated equally by T3 or T4. These stimulatory influences of T3/T4 over nerves likely arose as secondary consequences brought on by TH-mediated modulations to the corneal extracellular matrix. Specifically, we found that the levels of nerve-inhibitory keratan- and chondroitin-sulfate containing proteoglycans and associated sulfation enzymes were dramatically altered in the presence of exogenous T3 or T4. Altogether, these findings uncover new roles for TH on corneal development and shed insight into the mechanistic basis of both T3 and T4 on cornea innervation.

Galanin Signaling in the Brain Regulates Color Pattern Formation in Zebrafish.

SummaryColor patterns are prominent features of many animals and are of high evolutionary relevance. In basal vertebrates, color patterns are composed of specialized pigment cells that arrange in multilayered mosaics in the skin. Zebrafish (Danio rerio), the preeminent model system for vertebrate color pattern formation, allows genetic screens as powerful approaches to identify novel functions in a complex biological system. Adult zebrafish display a series of blue and golden horizontal stripes, composed of black melanophores, silvery or blue iridophores, and yellow xanthophores. This stereotyped pattern is generated by self-organization involving direct cell contacts between all three types of pigment cells mediated by integral membrane proteins [1, 2, 3, 4, 5]. Here, we show that neuropeptide signaling impairs the striped pattern in a global manner. Mutations in the genes coding either for galanin receptor 1A (npm/galr1A) or for its ligand galanin (galn) result in fewer stripes, a pale appearance, and the mixing of cell types, thus resembling mutants with thyroid hypertrophy [6]. Zebrafish chimeras obtained by transplantations of npm/galr1A mutant blastula cells indicate that mutant pigment cells of all three types can contribute to a normal striped pattern in the appropriate host. However, loss of galr1A expression in a specific region of the brain is sufficient to cause the mutant phenotype in an otherwise wild-type fish. Increased thyroid hormone levels in mutant fish suggest that galanin signaling through Galr1A in the pituitary is an upstream regulator of the thyroid hormone pathway, which in turn promotes precise interactions of pigment cells during color pattern formation.