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Bioorganic Chemistry Dec 2023Lactoperoxidase was previously used as a model enzyme to test the inhibitory activity of selenium analogs of anti-thyroid drugs with...
Lactoperoxidase was previously used as a model enzyme to test the inhibitory activity of selenium analogs of anti-thyroid drugs with 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as a substrate. Peroxidases oxidize ABTS to a metastable radical ABTS, which is readily reduced by many antioxidants, including thiol-containing compounds, and it has been used for decades to measure antioxidant activity in biological samples. We showed that anti-thyroid drugs 6-n-propyl-2-thiouracil, methimazole, and selenium analogs of methimazole also reduced it rapidly. This reaction may explain the anti-thyroid action of many other compounds, particularly natural antioxidants, which may reduce the oxidized form of iodine and/or tyrosyl radicals generated by thyroid peroxidase thus decreasing the production of thyroid hormones. However, influence of selenium analogs of methimazole on the rate of hydrogen peroxide consumption during oxidation of ABTS by lactoperoxidase was moderate. Direct hydrogen peroxide reduction, proposed before as their mechanism of action, cannot therefore account for the observed inhibitory effects. 1-Methylimidazole-2-selone and its diselenide were oxidized by ABTS to relatively stable seleninic acid, which decomposed slowly to selenite and 1-methylimidazole. In contrast, oxidation of 1,3-dimethylimidazole-2-selone gave selenite and 1,3-dimethylimidazolium cation. Accumulation of the corresponding seleninic acid was not observed.
Topics: Antioxidants; Cations; Hydrogen Peroxide; Lactoperoxidase; Methimazole; Oxidation-Reduction; Selenious Acid; Selenium; Propylthiouracil
PubMed: 37788560
DOI: 10.1016/j.bioorg.2023.106891 -
Scientific Reports Sep 2021Larval metamorphosis in bivalves is a key event for the larva-to-juvenile transformation. Previously we have identified a thyroid hormone receptor (TR) gene that is...
Larval metamorphosis in bivalves is a key event for the larva-to-juvenile transformation. Previously we have identified a thyroid hormone receptor (TR) gene that is crucial for larvae to acquire "competence" for the metamorphic transition in the mussel Mytilus courscus (Mc). The mechanisms of thyroid signaling in bivalves are still largely unknown. In the present study, we molecularly characterized the full-length of two iodothyronine deiodinase genes (McDx and McDy). Phylogenetic analysis revealed that deiodinases of molluscs (McDy, CgDx and CgDy) and vertebrates (D2 and D3) shared a node representing an immediate common ancestor, which resembled vertebrates D1 and might suggest that McDy acquired specialized function from vertebrates D1. Anti-thyroid compounds, methimazole (MMI) and propylthiouracil (PTU), were used to investigate their effects on larval metamorphosis and juvenile development in M. coruscus. Both MMI and PTU significantly reduced larval metamorphosis in response to the metamorphosis inducer epinephrine. MMI led to shell growth retardation in a concentration-dependent manner in juveniles of M. coruscus after 4 weeks of exposure, whereas PTU had no effect on juvenile growth. It is hypothesized that exposure to MMI and PTU reduced the ability of pediveliger larvae for the metamorphic transition to respond to the inducer. The effect of MMI and PTU on larval metamorphosis and development is most likely through a hormonal signal in the mussel M. coruscus, with the implications for exploring the origins and evolution of metamorphosis.
Topics: Animals; Antithyroid Agents; Iodide Peroxidase; Larva; Metamorphosis, Biological; Methimazole; Mytilus; Propylthiouracil; Thyroid Hormones
PubMed: 34588587
DOI: 10.1038/s41598-021-98930-9 -
Endocrinology, Diabetes & Metabolism... Jul 2022Graves' disease can have multiple cardiac manifestations. A rare complication is that of severe mitral regurgitation secondary to mitral valve chordae rupture, due to...
SUMMARY
Graves' disease can have multiple cardiac manifestations. A rare complication is that of severe mitral regurgitation secondary to mitral valve chordae rupture, due to both compromise of valve integrity by deposition of glycosaminoglycans and the hemodynamic stresses of thyrotoxicosis. Pregnancy, with its related hemodynamic changes, is another setting in which mitral valve chordae rupture has occasionally been documented. We present a unique case of a 36-year-old female with uncontrolled Graves' disease who presented during pregnancy at 13 weeks gestation with atrial flutter and features of congestive heart failure. Echocardiogram found severe mitral regurgitation secondary to a ruptured mitral chord. She was treated conservatively with diuresis and ultimately delivered her baby without complication at 28 weeks when she had preterm premature rupture of membranes. She is currently on methimazole and propranolol and pending definitive management of her Graves' disease. This represents not only a rare cardiac complication in a patient with Graves' disease but also is the first in the literature, to our knowledge, which describes this complication in a pregnant patient with Graves' disease.
LEARNING POINTS
Thyroid disease can have multiple effects on the heart through hemodynamic and structural changes and can result in heart failure, arrhythmias, valvular disease, and pulmonary hypertension. Graves' disease can cause glycosaminoglycan deposition in valvular tissue resulting in fragile leaflets that can rupture with little stress. Pregnancy and thyrotoxicosis have similar hemodynamic consequences with increased cardiac output and reduced systemic vascular resistance. Be vigilant in those with hyperthyroidism with a new murmur or features of acute heart failure, as a ruptured valve chord can result in increased morbidity and mortality if not recognized and addressed quickly.
PubMed: 35895699
DOI: 10.1530/EDM-22-0298 -
Indian Journal of Pharmacology 2016Some cases of acute pancreatitis have been reported to be associated with use of methimazole. The aim of this study was to investigate the relationship between use of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Some cases of acute pancreatitis have been reported to be associated with use of methimazole. The aim of this study was to investigate the relationship between use of methimazole and risk of acute pancreatitis on the basis of a systematic analysis.
METHODS
This was a population-based case-control study analyzing the database of the Taiwan National Health Insurance Program. There were 5764 individuals aged 20-84 years with a first attack of acute pancreatitis from 1998 to 2011 as the cases and 23,056 randomly selected sex- and age-matched individuals without acute pancreatitis as the controls. Use of methimazole was categorized as "never use" and "ever use." We estimated the relative risk of acute pancreatitis associated with the use of methimazole by calculating the odds ratio (OR) with 95% confidence interval (CI) using a multivariable logistic regression model.
RESULTS
After adjustment for confounding factors, the OR of acute pancreatitis was 0.91 in individuals with ever use of methimazole, when compared with individuals with never use of methimazole (95% CI, 0.60-1.38). Unlike methimazole use, alcohol-related disease, biliary stone, cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, hepatitis B, hepatitis C, and hypertriglyceridemia were factors significantly associated with acute pancreatitis.
CONCLUSIONS
Our study does not detect a substantial association between the use of methimazole and risk of acute pancreatitis on the basis of systematic analysis. There appears to be a discrepancy between case reports and our systematic analysis about the association between the use of methimazole and risk of acute pancreatitis.
Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Methimazole; Middle Aged; Pancreatitis; Taiwan; Young Adult
PubMed: 27127323
DOI: 10.4103/0253-7613.178841 -
Journal of Yeungnam Medical Science Jan 2023Graves disease (GD) is the most common cause of hyperthyroidism, accounting for more than 90% of cases in Korea. Patients with GD are treated with any of the following:...
Graves disease (GD) is the most common cause of hyperthyroidism, accounting for more than 90% of cases in Korea. Patients with GD are treated with any of the following: antithyroid drugs (ATDs), radioactive iodine (RAI) therapy, or thyroidectomy. Most patients begin treatment with ATDs, and clinical guidelines suggest that the appropriate treatment period is 12 to 18 months. While RAI treatment and surgery manage thyrotoxicosis by destroying or removing thyroid tissue, ATDs control thyrotoxicosis by inhibiting thyroid hormone synthesis and preserving the thyroid gland. Although ATDs efficiently control thyrotoxicosis symptoms, they do not correct the main etiology of GD; therefore, frequent relapses can follow. Recently, a large amount of data has been collected on long-term ATDs for GD, and low-dose methimazole (MMZ) is expected to be a good option for remission. For the long-term management of recurrent GD, it is important to induce remission by evaluating the patient's drug response, stopping ATDs at an appropriate time, and actively switching to surgery or RAI therapy, if indicated. Continuing drug treatment for an extended time is now encouraged in patients with a high possibility of remission with low-dose MMZ. It is also important to pay attention to the quality of life of the patients. This review aimed to summarize the appropriate treatment methods and timing of treatment transition in patients who relapsed several times while receiving treatment for GD.
PubMed: 36329661
DOI: 10.12701/jyms.2022.00444 -
The Libyan Journal of Medicine Dec 2023YKL-40, which is also known as Chitiniase 3-like 1, has been found to be up-regulated in many autoimmune diseases including asthma, systemic sclerosis and systemic...
YKL-40, which is also known as Chitiniase 3-like 1, has been found to be up-regulated in many autoimmune diseases including asthma, systemic sclerosis and systemic lupus, etc. However, the relationship between serum levels of YKL-40 and one another common autoinmmue thyroid disease - Graves' disease (GD) has not yet been investigated. The current study was performed to investigate the correlation of serum YKL-40 levels with disease severity of initially diagnosed GD. A total of 142 newly diagnosed active GD and 137 healthy individuals were enrolled in the study. Methimazole was given to 55 GD patients and then 2-month study of follow-up was performed. A commercial ELISA kit was applied for the detection of YKL-40 in serum. Degree of goiter was assessed according to Pérez's Grade. Receiver operating characteristic (ROC) curve analysis was carried out to detect the diagnostic value of serum YKL-40 with regard to goiter degree. The velocity of the peak systolic blood-flow and the thyroid tissue blood flow (TBF) were examined using Color Flow Doppler ultrasonography (CFDU). The patients with GD exhibited dramatically higher YKL-40 in serum compared to those of healthy controls (606.1 ± 149.8 pg/mL vs. 397.4 ± 95.1 pg/mL, < 0.001). Positive associations of YKL-40 with free T3 (FT3) and T4 (FT4), as well as the negative correlation of YKL-40 with TSH in serum, were observed. Additionally, the YKL-40 in serum was dramatically reduced after methimazole intervention, and the correlation of the decline with the reduced FT3 and FT4 was also found (all < 0.001). Serum YKL-40 levels were positively correlated with goiter degree. ROC curve analysis demonstrated that serum YKL-40 concentration may act as a decent marker for goiter degree. The positive correlations of YKL-40 in serum with the average superior thyroid artery velocity (STV) and thyroid tissue blood flow (TBF) were also observed. Our findings implicated that YKL-40 may be closely connected to the pathogenesis of GD. Increased YKL-40 levels are linked with disease severity of initially diagnosed GD.
Topics: Humans; Methimazole; Chitinase-3-Like Protein 1; Graves Disease; Patient Acuity
PubMed: 37199347
DOI: 10.1080/19932820.2023.2212480 -
Zhongguo Dang Dai Er Ke Za Zhi =... Nov 2022To investigate the incidence rate of adverse reactions of methimazole in children with hyperthyroidism.
OBJECTIVES
To investigate the incidence rate of adverse reactions of methimazole in children with hyperthyroidism.
METHODS
A retrospective analysis was performed on the medical data of 304 children with hyperthyroidism who were hospitalized in Shengjing Hospital of China Medical University from January 2015 to May 2021. The incidence rate of methimazole-related adverse reactions was analyzed. The risk factors for common adverse reactions were evaluated.
RESULTS
Among the 304 children, 87 (28.6%) experienced adverse reactions, among whom there were 20 boys (23%) and 67 girls (77%). Common adverse reactions included neutropenia (12.8%), rash (11.8%), elevated alanine aminotransferase (9.5%), and joint pain (3.0%), and some children experienced multiple adverse reactions simultaneously or intermittently. Neutropenia often occurred within 3 months after administration (25/39, 64%), elevated alanine aminotransferase often occurred within 1 month after administration (17/29, 59%), and rash often occurred within 3 months after administration (30/36, 83%). Most of the above adverse reactions returned to normal after symptomatic treatment. The multivariate logistic regression analysis showed that younger age and lower absolute neutrophil count before treatment were risk factors for neutropenia after methimazole treatment (<0.05).
CONCLUSIONS
The adverse reactions of methimazole are common in children with hyperthyroidism, and most adverse reactions occur within 3 months after administration and can be relieved after symptomatic treatment. Children with a younger age or a lower baseline absolute neutrophil count may have a higher risk of neutropenia.
Topics: Male; Child; Female; Humans; Methimazole; Antithyroid Agents; Retrospective Studies; Alanine Transaminase; Hyperthyroidism; Neutropenia; Exanthema
PubMed: 36398552
DOI: 10.7499/j.issn.1008-8830.2205022 -
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 -
The Journal of Endocrinology Jun 2018Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of both metabolic and inflammatory diseases and has become the leading chronic liver disease...
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of both metabolic and inflammatory diseases and has become the leading chronic liver disease worldwide. High-fat (HF) diets promote an increased uptake and storage of free fatty acids (FFAs) and triglycerides (TGs) in hepatocytes, which initiates steatosis and induces lipotoxicity, inflammation and insulin resistance. Activation and signaling of Toll-like receptor 4 (TLR4) by FFAs induces inflammation evident in NAFLD and insulin resistance. Currently, there are no effective treatments to specifically target inflammation associated with this disease. We have established the efficacy of phenylmethimazole (C10) to prevent lipopolysaccharide and palmitate-induced TLR4 signaling. Because TLR4 is a key mediator in pro-inflammatory responses, it is a potential therapeutic target for NAFLD. Here, we show that treatment with C10 inhibits HF diet-induced inflammation in both liver and mesenteric adipose tissue measured by a decrease in mRNA levels of pro-inflammatory cytokines. Additionally, C10 treatment improves glucose tolerance and hepatic steatosis despite the development of obesity due to HF diet feeding. Administration of C10 after 16 weeks of HF diet feeding reversed glucose intolerance, hepatic inflammation, and improved hepatic steatosis. Thus, our findings establish C10 as a potential therapeutic for the treatment of NAFLD.
Topics: Adipose Tissue; Animals; Cells, Cultured; Cytoprotection; Diet; Glucose Intolerance; Hep G2 Cells; Hepatocytes; Humans; Inflammation; Liver; Male; Methimazole; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity; Thiones; Triglycerides
PubMed: 29666152
DOI: 10.1530/JOE-18-0078 -
Journal of Clinical Medicine Oct 2023Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism.
BACKGROUND
Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism.
METHODOLOGY
Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves' disease ( = 21), amiodarone-induced thyrotoxicosis ( = 7), and hyperfunctioning multinodular goiter ( = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil.
RESULTS
The median (IQR) time to development of agranulocytosis was 6.0 (4.0-11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves' disease), and two patients died of septic shock secondary to AIA.
CONCLUSIONS
AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously.
PubMed: 37892693
DOI: 10.3390/jcm12206556