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Journal of Fluorescence Apr 2024Herein, an aqueous phase synthesis approach was presented for the fabrication of copper nanoclusters (Cu NCs) with aggregation-induced emission (AIE) property, utilizing...
Herein, an aqueous phase synthesis approach was presented for the fabrication of copper nanoclusters (Cu NCs) with aggregation-induced emission (AIE) property, utilizing lipoic acid and NaBH as ligands and reducing agent, respectively. The as-synthesized Cu NCs exhibit an average size of 3.0 ± 0.2 nm and demonstrate strong solid-state fluorescence upon excitation with UV light. However, when dissolved in water, no observable fluorescent emission is detected in the aqueous solution of Cu NCs. Remarkably, the addition of Methimazole induced a significant red fluorescence from the aqueous solution of Cu NCs. This unexpected phenomenon can be ascribed to the aggregation of negatively charged Cu NCs caused by electrostatic interaction with positively charged imidazole groups in Methimazole, resulting in enhanced fluorescence through AIE mechanism. Therefore, there exists an excellent linear correlation between the fluorescent intensities of Cu NCs aqueous solution and the concentration of Methimazole within a range of 0.1-1.5 mM with a low limit of detection of 82.2 µM. Importantly, the designed enhanced-fluorescent nanoprobe based on Cu NCs exhibits satisfactory performance in assaying commercially available Methimazole tablets, demonstrating its exceptional sensitivity, reliability, and accuracy.
PubMed: 38652358
DOI: 10.1007/s10895-024-03701-0 -
Journal of Medical Cases Apr 2024In pediatric-aged patients, hyperthyroidism generally results from the autoimmune disorder, Graves' disease (GD). Excessive levels of thyroid hormones (triiodothyronine...
In pediatric-aged patients, hyperthyroidism generally results from the autoimmune disorder, Graves' disease (GD). Excessive levels of thyroid hormones (triiodothyronine and thyroxine) result in irritability, emotional lability, nervousness, tremors, palpitations, tachycardia, and arrhythmias. The risk of morbidity and mortality is increased when surgical intervention is required in patients with hyperthyroidism due to the potential for the development of thyroid storm (TS). A 3-year, 1-month-old child with a past medical history of GD presented for total thyroidectomy when pharmacologic control with methimazole was not feasible due to intolerance following development of a serum sickness-like illness. Prior to surgery, his thyrotoxicosis symptoms worsened with fever, tachycardia, diaphoresis, and hypertension. He subsequently developed TS and was admitted to the pediatric intensive care unit where management included hydrocortisone, potassium iodide, and β-adrenergic blockade with esmolol and propranolol. Thyroid studies improved prior to surgery, and a total thyroidectomy was successfully completed. Corticosteroid therapy was slowly tapered as an outpatient, and he was discharged home on hospital day 9. Following discharge, his signs and symptoms of thyrotoxicosis resolved, and he was started on oral levothyroxine replacement therapy. The remainder of his postoperative and post-discharge course were unremarkable. Only two case reports of perioperative pediatric TS have been published in the past 20 years. Our case serves as an important reminder of the signs of TS in children and to outline the treatment options in a pediatric patient, especially in those unable to tolerate first-line pharmacologic therapies such as methimazole or propylthiouracil.
PubMed: 38646421
DOI: 10.14740/jmc4197 -
IBRO Neuroscience Reports Jun 2024Ginsenoside Rg1(Rg1), a monomer of a tetracyclic triterpenoid derivative, possesses diverse medicinal properties attributed to its unique chemical structure and may have...
Protective role of the ginsenoside Rg1 against methimazole-induced gestational hypothyroidism on reflexive behaviors, conditioned fear and cortical antioxidant levels in mice offspring.
Ginsenoside Rg1(Rg1), a monomer of a tetracyclic triterpenoid derivative, possesses diverse medicinal properties attributed to its unique chemical structure and may have beneficial effects on fetal development. This study aimed to investigate the protective effects of prenatal exposure to Rg1 against Methimazole-induced gestational hypothyroidism on reflexive behaviors, conditioned fear, and cortical antioxidant levels in mouse offspring.40 female virgin mice and 12 male NMRI mice were assigned to four groups: group 1 served as the control, group 2 received Methimazole(MMI) at a concentration of 0.02% in their drinking water, group 3 received Rg1(150 mg/kg), and group 4 received both MMI and Rg1.Groups of 2-4 were administered the substances from days 1-9 of gestation. After delivery, pups were selected, and reflexive motor behaviors and conditioned fear were assessed. Additionally, levels of brain tissue catalase(CAT), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione peroxidase(GPx) levels were measured. Furthermore, postpartum immobility time in the forced swimming test (FST), tail suspension test (TST), and the number of squares crossed in the open field test (OFT)were determined. The results demonstrated that maternal exposure to Rg1 improved ambulation score, hind-limb suspension score, grip strength, front-limb suspension, hind-limb foot angle, negative geotaxis, surface righting, and conditioned fear in hypothyroidism-induced offspring(<0.05). Rg1 decreased immobility time in the FST, and TST, and increased the number of squares crossed in the OFT in postpartum hypothyroidism-induced mice(<0.05). Moreover, Rg1 reduced brain tissue MDA levels and increased brain tissue CAT, SOD, and GPx levels in mice and their offspring(<0.05). These findings indicate that Rg1 mitigated postpartum depression in mice and improved reflexive motor behaviors in their pups.
PubMed: 38634016
DOI: 10.1016/j.ibneur.2024.03.010 -
Cureus Apr 2024Insulin autoimmune syndrome (IAS) or Hirata disease is a rare condition presenting as recurrent hypoglycemia, and associated with elevated insulin levels in the presence...
Insulin autoimmune syndrome (IAS) or Hirata disease is a rare condition presenting as recurrent hypoglycemia, and associated with elevated insulin levels in the presence of insulin autoantibodies (IAAs) in patients who were never exposed to exogenous insulin and with no evidence of pancreatic abnormalities. IAS is much more frequent in East Asians, especially the Japanese population, compared to the lower incidence in Caucasians. However, it can be associated with other autoimmune diseases or drug use like methimazole and alpha-lipoic acid (ALA). We report a case of a 47-year-old Caucasian male presenting with a 12-month history of worsening episodes of fasting and post-prandial hypoglycemia associated with symptoms of dizziness, tremors, palpitations, and unconsciousness associated with hypoglycemia. Symptoms resolved with the administration of carbohydrate-containing foods, establishing Whipple's triad. At an outside facility, he had initial labs that showed elevated insulin levels (141 µU/ml) with normal glucose, C-peptide, and proinsulin levels, but there was no availability of an IAA lab assay. Given his symptoms, severity, and frequency of hypoglycemia, he was admitted to the hospital for a 72-hour fast, which showed the lowest glucose level of 64 mg/dl with inappropriately high insulin of 22.2 µU/ml, low C-peptide of 0.57 ng/ml, and undetectable proinsulin of <1.6 pmol/L, but with IAA being >50 U/ml (0.0-0.4 U/ml). He was treated with intensive dietary counseling with a low-carbohydrate diet and prednisone 20 mg twice daily initially. Additionally, he could not tolerate octreotide, diazoxide, and acarbose due to side effects. He is currently on prednisone 10 mg daily and nifedipine with no further hypoglycemic episodes, but still has a high IAA of >50 U/ml and serum insulin levels of 70-112 µU/ml. Our case highlights the importance of recognizing hypoglycemia and checking for IAA levels as first-line diagnostic tests, in the absence of which there could be a delay in diagnosis and leading to unnecessary lab and imaging testing. Our case is unique since it happened in a Caucasian without any prior exposure to a triggering factor and has not undergone self-remission yet, which happens in most of IAS cases.
PubMed: 38623323
DOI: 10.7759/cureus.58270 -
Thyroid : Official Journal of the... Jun 2024Agranulocytosis is a rare antithyroid drug treatment (ATD) side effect seen in children suffering from Graves' disease (GD). Neutropenia is a recognized adverse event...
Agranulocytosis is a rare antithyroid drug treatment (ATD) side effect seen in children suffering from Graves' disease (GD). Neutropenia is a recognized adverse event associated with ATD but has also been reported as pre-treatment neutropenia in GD. We performed a retrospective cohort study to analyze the longitudinal clinical and biochemical data of 161 pediatric patients with GD who received either methimazole (MMI) or carbimazole (CBZ) as ATD. The inclusion criteria were elevated free thyroxine (fT4 >25 pmol/L), suppressed thyrotropin (TSH <0.05 mlU/mL), and elevated thyrotropin receptor antibodies (TSHRAbs >2.5 IU/L). Absolute neutrophil count (ANC) was used to define neutropenia (ANC <1800/µL) and agranulocytosis (ANC <500/µL). Nine of the 161 patients had neutropenia at diagnosis (ANC: 1348/µL ± 250) without further deterioration under ATD. In this subgroup, we found higher levels of free triiodothyronine (fT3: 31.45 pmol/L ± 3.99) at diagnosis in comparison with those who developed neutropenia (26.29 pmol/L ± 12.96; = 0.07) and those without neutropenia before and during therapy (23.12 pmol/L ± 13.7; = 0.003). Thirty-eight patients (23.6%) became neutropenic (ANC: 1479/µL ± 262) while receiving ATD. Neutropenia occurred after a mean of 551.8 (range: 10-1376) days, mostly without further deterioration. Two of these 38 patients developed agranulocytosis and underwent emergency thyroidectomy. The patients with neutropenia were significantly younger ( = 0.031). Neutropenia occurred significantly more often in patients receiving CBZ (50%; = 20/40) than in those receiving MMI (16.5%; = 18/110; = 0.001). The minimum ANC was significantly lower in the CBZ (1971/µL ± 1008) than in the MMI group (2546 ± 959); = 0.004. Neutropenia occurred significantly more often under CBZ than MMI. As this is potentially due to higher immunogenicity, we suggest that children with GD should be treated with MMI. Frequent measurements of ANC may be needed to detect severe agranulocytosis, although low pre-treatment ANC may not necessarily be a contraindication to ATD treatment. Young age may be potentially associated with an increased risk of reduced ANC. Further investigation is necessary to fully understand risk factors for neutropenia in children with GD.
Topics: Humans; Methimazole; Child; Neutropenia; Antithyroid Agents; Female; Male; Retrospective Studies; Graves Disease; Adolescent; Carbimazole; Child, Preschool; Agranulocytosis; Thyroxine; Thyrotropin; Triiodothyronine
PubMed: 38613811
DOI: 10.1089/thy.2023.0673 -
Heliyon Apr 2024Thyroid storm (TS) leading to acute liver failure is rare but fatal in clinical practice and hepatic failure can remarkably limit medication options for TS. We...
Case report and literature review: A thyroid storm patient with severe acute hepatic failure treated by therapeutic plasma exchange and a double plasma molecular absorption system.
Thyroid storm (TS) leading to acute liver failure is rare but fatal in clinical practice and hepatic failure can remarkably limit medication options for TS. We successfully cured a patient with TS complicated with acute hepatic failure using therapeutic plasma exchange (TPE) and a double plasma molecular absorption system (DPMAS) and summarized the case characteristics of 10 similar critical patients reported worldwide. We recommend that patients with TS complicated with liver failure disuse propylthiouracil or methimazole. TPE should be utilized to rapidly decrease thyroid hormone levels, and DPMAS should be considered for supportive treatment in the presence of hepatic encephalopathy or dramatic bilirubin elevations.
PubMed: 38601545
DOI: 10.1016/j.heliyon.2024.e28867 -
Journal of Applied Toxicology : JAT Apr 2024Although measurements of blood triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels in rodent toxicity studies are useful for detection of...
Comparison of the sensitivity of histopathological and immunohistochemical analyses and blood hormone levels for early detection of antithyroid effects in rats treated with thyroid peroxidase inhibitors.
Although measurements of blood triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels in rodent toxicity studies are useful for detection of antithyroid substances, assays for these measurements are expensive and can show high variability depending on blood sampling conditions. To develop more efficient methods for detecting thyroid disruptors, we compared histopathological and immunohistochemical findings in the thyroid and pituitary glands with blood hormone levels. Six-week-old male and female Sprague-Dawley rats (five rats per group) were treated with multiple doses of the thyroid peroxidase inhibitors propylthiouracil (PTU) and methimazole by gavage for 28 days. Significant decreases in serum T3 and T4 and increases in TSH were observed in the ≥1 mg/kg PTU and ≥3 mg/kg methimazole groups. An increase in TSH was also detected in male rats in the 0.3 mg/kg PTU group. Histopathological and immunohistochemical analyses revealed that follicular cell hypertrophy and decreased T4 and T3 expressions in the thyroid gland were induced at doses lower than doses at which significant changes in serum hormone levels were observed, suggesting that these findings may be more sensitive than blood hormone levels. Significant increases in thyroid weights, Ki67-positive thyroid follicular cell counts, and TSH-positive areas in the pituitary gland were detected at doses comparable with those at which changes in serum T4 and TSH levels were observed, indicating that these parameters may also be useful for evaluation of antithyroid effects. Combining these parameters may be effective for detecting antithyroid substances without relying on hormone measurements.
PubMed: 38563354
DOI: 10.1002/jat.4604 -
Journal of Translational Medicine Mar 2024A subset of Graves' disease (GD) patients develops refractory hyperthyroidism, posing challenges in treatment decisions. The predictive value of baseline characteristics...
BACKGROUND
A subset of Graves' disease (GD) patients develops refractory hyperthyroidism, posing challenges in treatment decisions. The predictive value of baseline characteristics and early therapy indicators in identifying high risk individuals is an area worth exploration.
METHODS
A prospective cohort study (2018-2022) involved 597 newly diagnosed adult GD patients undergoing methimazole (MMI) treatment. Baseline characteristics and 3-month therapy parameters were utilized to develop predictive models for refractory GD, considering antithyroid drug (ATD) dosage regimens.
RESULTS
Among 346 patients analyzed, 49.7% developed ATD-refractory GD, marked by recurrence and sustained Thyrotropin Receptor Antibody (TRAb) positivity. Key baseline factors, including younger age, Graves' ophthalmopathy (GO), larger goiter size, and higher initial free triiodothyronine (fT3), free thyroxine (fT4), and TRAb levels, were all significantly associated with an increased risk of refractory GD, forming the baseline predictive model (Model A). Subsequent analysis based on MMI cumulative dosage at 3 months resulted in two subgroups: a high cumulative dosage group (average ≥ 20 mg/day) and a medium-low cumulative dosage group (average < 20 mg/day). Absolute values, percentage changes, and cumulative values of thyroid function and autoantibodies at 3 months were analyzed. Two combined predictive models, Model B (high cumulative dosage) and Model C (medium-low cumulative dosage), were developed based on stepwise regression and multivariate analysis, incorporating additional 3-month parameters beyond the baseline. In both groups, these combined models outperformed the baseline model in terms of discriminative ability (measured by AUC), concordance with actual outcomes (66.2% comprehensive improvement), and risk classification accuracy (especially for Class I and II patients with baseline predictive risk < 71%). The reliability of the above models was confirmed through additional analysis using random forests. This study also explored ATD dosage regimens, revealing differences in refractory outcomes between predicted risk groups. However, adjusting MMI dosage after early risk assessment did not conclusively improve the prognosis of refractory GD.
CONCLUSION
Integrating baseline and early therapy characteristics enhances the predictive capability for refractory GD outcomes. The study provides valuable insights into refining risk assessment and guiding personalized treatment decisions for GD patients.
Topics: Adult; Humans; Secondary Prevention; Prospective Studies; Reproducibility of Results; Hyperthyroidism; Antithyroid Agents; Graves Disease
PubMed: 38553734
DOI: 10.1186/s12967-024-05129-3 -
Clinical Practice and Cases in... Feb 2024Thyroid storm is a rare but potentially life-threatening metabolic disorder that presents unique management challenges in the emergency department. Thionamides are...
INTRODUCTION
Thyroid storm is a rare but potentially life-threatening metabolic disorder that presents unique management challenges in the emergency department. Thionamides are commonly used as monotherapy for first-line treatment of hyperthyroidism.
CASE REPORT
In this case, a 26-year-old male presented to the emergency department with sore throat, fever, and diarrhea. He was found to have thyrotoxicosis as well as methimazole-induced bone marrow suppression resulting in agranulocytosis.
CONCLUSION
Thyroid storm is a rare condition that carries a high risk of mortality and can further compromise a patient's immune system due to complications of common treatment modalities. It can potentially be misdiagnosed as sepsis due to tachycardia, febrile state, and tachypnea. This case report includes a discussion of diagnostic studies, as well as medical and surgical treatment modalities that led to the patient's recovery.
PubMed: 38546308
DOI: 10.5811/cpcem.6609 -
Animals : An Open Access Journal From... Mar 2024In recent years, nitrate (NO-N) pollution in water bodies has been increasing due to the excessive use of nitrogen-based fertilizers. Exposure to NO-N during the...
In recent years, nitrate (NO-N) pollution in water bodies has been increasing due to the excessive use of nitrogen-based fertilizers. Exposure to NO-N during the development of amphibian embryos may have lasting effects on the growth and development of individuals and even threaten their survival, but the toxicity mechanism of NO-N in amphibian embryos prior to thyroid morphogenesis remains unclear. In the present study, was selected as the model organism to investigate the toxic effects of 10 mg/L and 100 mg/L NO-N exposure (N10 and N100) on amphibian embryos using methimazole (MMI) and exogenous thyroxine (T4) as the reference groups. We found that T4, MMI, N10 and N100 inhibited embryo growth and development, with MMI and N100 showing the earliest and strongest effects. Transcriptome analysis revealed that MMI and NO-N (especially N100) significantly downregulated genes related to thyroid morphogenesis and cholesterol metabolism, while upregulating genes related to inflammation and apoptosis. Together, these results contribute to a deeper understanding of the complex mechanisms by which NO-N disrupts embryonic development, reveal the potential risks of NO-N pollution to other aquatic organisms, and provide insights into the conservation of a broader ecosystem.
PubMed: 38540059
DOI: 10.3390/ani14060961