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Endocrinology and Metabolism (Seoul,... Jun 2021Graves' disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through...
Graves' disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through inhibition of thyroid hormone synthesis or destruction of the thyroid gland. Recurrence after antithyroid drug (ATD) treatment is common. Recent studies have shown that the longer is the duration of use of ATD, the higher is the remission rate. Considering the relationship between clinical outcomes and iodine intake, recurrence of Graves' disease is more common in iodine-deficient areas than in iodine-sufficient areas. Iodine restriction in an iodine-excessive area does not improve the effectiveness of ATD or increase remission rates. Recently, Danish and Korean nationwide studies noted significantly higher prevalence of birth defects in newborns exposed to ATD during the first trimester compared to that of those who did not have such exposure. The prevalence of birth defects was lowest when propylthiouracil (PTU) was used and decreased by only 0.15% when methimazole was changed to PTU in the first trimester. Therefore, it is best not to use ATD in the first trimester or to change to PTU before pregnancy.
Topics: Antithyroid Agents; Female; Graves Disease; Humans; Infant, Newborn; Methimazole; Pregnancy; Propylthiouracil; Thyrotropin
PubMed: 34130446
DOI: 10.3803/EnM.2021.1070 -
Chemical Research in Toxicology Dec 2021Methimazole (MMI) is a widely used antithyroid drug, but it can cause hepatotoxicity by unknown mechanisms. Previous studies showed that the hepatic metabolism of MMI...
Methimazole (MMI) is a widely used antithyroid drug, but it can cause hepatotoxicity by unknown mechanisms. Previous studies showed that the hepatic metabolism of MMI produces -methylthiourea, leading to liver damage. However, the specific enzyme responsible for the production of the toxic metabolite -methylthiourea is still unclear. In this study, we screened cytochromes P450 (CYPs) in -methylthiourea production from MMI. CYP2A6 was identified as the key enzyme in catalyzing MMI metabolism to produce -methylthiourea. When mice were pretreated with a CYP2A6 inhibitor, formation of -methylthiourea from MMI was remarkably reduced. Consistently, the CYP2A6 inhibitor prevented MMI-induced hepatotoxicity. These results demonstrated that CYP2A6 is essential in MMI bioactivation and hepatotoxicity.
Topics: Animals; Cytochrome P-450 CYP2A6; Cytochrome P-450 Enzyme Inhibitors; Humans; Liver; Male; Methimazole; Mice; Molecular Structure; Recombinant Proteins; Thiourea; Tranylcypromine
PubMed: 34788025
DOI: 10.1021/acs.chemrestox.1c00300 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Nov 2022Here, we reported two cases with hyperthyroidism who complained of myalgia and muscle cramps during treatment with methimazole tablets (or Thyrozol, the brand name). One...
Here, we reported two cases with hyperthyroidism who complained of myalgia and muscle cramps during treatment with methimazole tablets (or Thyrozol, the brand name). One case experienced muscle cramps after taking Thyrozol for 6 months, and by this time the patient's thyroid function had returned to normal. In the other case, pain caused by muscular cramps began after the patient took Thyrozol for two weeks and the patient's thyroid function had not returned to normal yet at the time. In both cases, pain caused by muscle cramps appeared while the patients were taking Thyrozol. The myalgia persisted in spite of a reduction in the Thyrozol dose, but was significantly relieved with the discontinuation of Thyrozol. Myalgia and muscle cramps did not recur after the patients were switched to methimazole ointment. There was a strong temporal association between oral administration of Thyrozol and pain caused by muscle cramps, which may indicate that myalgia and muscle cramps are adverse reactions of Thyrozol. Looking into the relevant literature on the topic, we explored in this report the possible mechanisms of the onset of muscle cramps associated with Thyrozol, and compared the adverse reactions of two different formulations of methimazole, intending to provide more clinical experience for the treatment of hyperthyroidism and the management of rare adverse reactions related to antithyroid drugs.
Topics: Humans; Methimazole; Muscle Cramp; Myalgia; Hyperthyroidism; Tablets
PubMed: 36443057
DOI: 10.12182/20221160210 -
Cureus Jun 2023Graves' disease (GD) may increase the difficulty of glucose control in patients with type 2 diabetes mellitus (T2DM). Therefore, selecting a drug with limited blood... (Review)
Review
Graves' disease (GD) may increase the difficulty of glucose control in patients with type 2 diabetes mellitus (T2DM). Therefore, selecting a drug with limited blood glucose side effects is an important issue in patients with T2DM and GD. Antithyroid drugs (ATDs) including propylthiouracil (PTU), methimazole, and carbimazole are commonly prescribed for the treatment of GD. Here, we review and summarize the literature from the last 10 years and discuss the effects of current ATDs used for GD for blood glucose control in patients with T2DM. A search of the literature published between January 1, 2012 and December 1, 2022 was conducted using three major medical databases: Google Scholar, Ovid Medline, and Scopus. An initial search was conducted on PubMed using the MeSH terms "propylthiouracil," "methimazole," "carbimazole," and "hyperglycemia" or "hypoglycemia" in academic databases. All articles included "Graves' disease" and "type 2 diabetes mellitus" in the title. Based on the results of previous studies, the hyperglycemic and hypoglycemic side effects of ATDs can be explained by several possible mechanisms. The most widely accepted hypothesis is that sulfhydryl group drugs (e.g., methimazole and carbimazole) cleave the disulfide bond of insulin and enhance its immunogenicity, resulting in hypoglycemia. Moreover, some reports have indicated that methimazole is associated with hypoglycemia; therefore, if the patient has a history of autoimmune diseases, it is necessary to consider whether to change drugs or actively track the production of autoimmune antibodies. In non-diabetic and diabetic patients with GD, the hyperglycemic and hypoglycemic side effects of PTU (on glycemic variation) were less than that of thiamazole. However, as relatively few reports have investigated the side effects of blood sugar changes, further research is necessary to confirm these effects. In addition to autoimmune diseases, drug side effects may need to be considered. These findings provide considerations for clinicians to select more appropriate ATDs for patients with GD and T2DM, and implement improved care guidelines.
PubMed: 37519546
DOI: 10.7759/cureus.41017 -
Thyroid : Official Journal of the... Nov 2020Thionamides have been extensively used to treat patients with hyperthyroidism worldwide. Recent pharmacovigilance studies have revealed a safety signal between...
Thionamides have been extensively used to treat patients with hyperthyroidism worldwide. Recent pharmacovigilance studies have revealed a safety signal between carbimazole or methimazole and pancreatitis. The associated risk remains unclear. We identified patients with newly diagnosed acute pancreatitis from 2000 to 2013 as the case group from the Taiwan Longitudinal Health Insurance Database 2000, which contains data from 1996 to 2013. Each patient with acute pancreatitis was matched for age, sex, comorbidities, and cancer with four controls through propensity score matching. A total of 52 patients without matched controls were excluded. Sensitivity analyses including the 52 excluded patients were performed using a matching ratio of 1:2. Odds ratios (ORs) along with 95% confidence intervals (CIs) for the association were estimated using multivariate logistic regression. We included 9204 and 36,816 patients in the case and control groups, respectively. The proportions of patients who had used thionamides, carbimazole, methimazole, and propylthiouracil were similar in these two groups. In addition, the adjusted OR (CI) for the association of acute pancreatitis with thionamides was 1.03 (0.86-1.24), with carbimazole it was 0.90 (0.63-1.30), with methimazole it was 1.05 (0.84-1.31), and with propylthiouracil it was 1.00 (0.74-1.34). The sensitivity analysis results were unchanged. We were unable to demonstrate an association between acute pancreatitis and usage of thionamides.
Topics: Adult; Aged; Antithyroid Agents; Carbimazole; Case-Control Studies; Comorbidity; Databases, Factual; Female; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Multivariate Analysis; Odds Ratio; Pancreatitis; Pharmacovigilance; Propylthiouracil; Retrospective Studies; Risk; Taiwan; Thioamides
PubMed: 32380933
DOI: 10.1089/thy.2019.0589 -
Frontiers in Immunology 2021Graves' disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly...
Graves' disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly used drug for the treatment of GD, the efficacy of methimazole is only limited to the control of clinical indicators, and the side effects of MI should be seriously considered. Here, we designed a 6-month clinical trial that divided the patients into two groups: a methimazole group (=8) and a methimazole combined with potential prebiotic berberine group (=10). The effects of both treatments on thyroid function and treatment outcomes in patients with GD were assessed by thyroid index measurements and gut microbiota metagenomic sequencing. The results showed that the addition of berberine restored the patients' TSH and FT3 indices to normal levels, whereas MI alone restored only FT3. In addition, TRAb was closer to the healthy threshold at the end of treatment with the drug combination. MI alone failed to modulate the gut microbiota of the patients. However, the combination of berberine with methimazole significantly altered the microbiota structure of the patients, increasing the abundance of the beneficial bacteria while decreasing the abundance of the pathogenic bacteria and . Furthermore, further mechanistic exploration showed that the addition of berberine resulted in a significant upregulation of the synthesis of enterobactin, which may have increased iron functioning and thus restored thyroid function. In conclusion, methimazole combined with berberine has better efficacy in patients with GD, suggesting the potential benefit of berberine combined with methimazole in modulating the composition of intestinal microbes in the treatment of GD, providing new strong evidence for the effectiveness of combining Chinese and Western drugs from the perspective of modulating the intestinal microbiota.
Topics: Berberine; Biomarkers; Disease Management; Drug Therapy, Combination; Dysbiosis; Gastrointestinal Microbiome; Graves Disease; Humans; Metabolic Networks and Pathways; Metagenome; Metagenomics; Methimazole; Models, Biological; Prebiotics; Thyroid Function Tests; Treatment Outcome
PubMed: 35082799
DOI: 10.3389/fimmu.2021.826067 -
Frontiers in Endocrinology 2023Methimazole (MMI) represents the conventional therapeutic agent for Graves' disease (GD) hyperthyroidism, but MMI efficacy is limited since it marginally affects the...
INTRODUCTION
Methimazole (MMI) represents the conventional therapeutic agent for Graves' disease (GD) hyperthyroidism, but MMI efficacy is limited since it marginally affects the underlying autoimmune process. In a previous study, we randomly assigned 42 newly diagnosed GD patients with insufficient vitamin D (VitD) and selenium (Se) levels to treatment with MMI alone (standard) or combined with selenomethionine and cholecalciferol (intervention) and observed a prompter resolution of hyperthyroidism in the intervention group.
METHODS
In the present study, we aimed to explore changes in peripheral T regulatory (Treg) and circulating natural killer (NK) cell frequency, circulating NK cell subset distribution and function, during treatment.
RESULTS
At baseline, circulating total CD3CD56NK cells and CD56 NK cells were significantly higher in GD patients than in healthy controls (HC) (15.7 ± 9.6% vs 9.9 ± 5.6%, p=0.001; 12.2 ± 10.3% vs 7.3 ± 4.1%, p=0.02, respectively); no differences emerged in Treg cell frequency. Frequencies of total NK cells and CD56 NK cells expressing the activation marker CD69 were significantly higher in GD patients than in HC, while total NK cells and CD56 NK cells expressing CD161 (inhibitory receptor) were significantly lower. When co-cultured with the K562 target cell, NK cells from GD patients had a significantly lower degranulation ability compared to HC (p<0.001). Following 6 months of treatment, NK cells decreased in both the intervention and MMI-alone groups, but significantly more in the intervention group (total NK: -10.3%, CI 95% -15.8; -4.8% vs -3.6%, CI 95% -9; 1.8%, p=0.09 and CD56 NK cells: -6.5%, CI 95% -10.1; -3 vs -0.9%, CI 95% -4.4; 2%, p=0.03). Compared to baseline, CD69 NK cells significantly decreased, while degranulation ability slightly improved, although no differences emerged between the two treatment groups. Compared to baseline, Treg cell frequency increased exclusively in the intervention group (+1.1%, CI 95% 0.4; 1.7%).
DISCUSSION
This pilot study suggested that VitD and Se supplementation, in GD patients receiving MMI treatment, modulates Treg and NK cell frequency, favoring a more pronounced reduction of NK cells and the increase of Treg cells, compared to MMI alone. Even if further studies are needed, it is possible to speculate that this immunomodulatory action might have facilitated the prompter and better control of hyperthyroidism in the supplemented group observed in the previous study.
Topics: Humans; Methimazole; Antithyroid Agents; Selenium; Vitamin D; Pilot Projects; Graves Disease; Hyperthyroidism; Vitamins; Dietary Supplements
PubMed: 37124743
DOI: 10.3389/fendo.2023.1145811 -
Journal of Clinical Research in... Apr 2023Thyroid storm is a rare but life-threatening condition mainly triggered by infection and abrupt discontinuation of antithyroid drug therapy for Graves' disease....
Thyroid storm is a rare but life-threatening condition mainly triggered by infection and abrupt discontinuation of antithyroid drug therapy for Graves' disease. Pancytopenia is a rare adverse reaction to antithyroid drugs. We present a 13-year-old girl with thyroid storm and pancytopenia with symptoms similar to those of methimazole-induced pancytopenia. Although in this context the use of methimazole is still under debate, due to multiple normal complete blood counts monitored during fever, sepsis-induced pancytopenia with thyroid storm was considered, and methimazole treatment combined with methylprednisolone and meropenem was able to resolve both pancytopenia and thyroid storm. During the period of infection and antithyroid drug therapy, close monitoring of complete blood count may help differentiate the aetiology of pancytopenia. This is the first paediatric case report that outlines the use of methimazole in the management of thyroid storm with pancytopenia.
PubMed: 37074093
DOI: 10.4274/jcrpe.galenos.2023.2022-10-3 -
The Journal of Clinical Endocrinology... Jan 2024In 2005, a nationwide program of iodine prophylaxis on a voluntary basis was implemented in Italy by law. However, recent data on iodine status are lacking.
CONTEXT
In 2005, a nationwide program of iodine prophylaxis on a voluntary basis was implemented in Italy by law. However, recent data on iodine status are lacking.
OBJECTIVE
The aim of this study was to evaluate efficiency, effectiveness, and possible adverse effects (increased occurrence of thyroid autoimmunity and hyperthyroidism) of the Italian iodine prophylaxis program.
METHODS
From 2015 to 2019, a nationwide survey was performed. The use of iodized salt was evaluated in a sample of 164 593 adults and in 998 school canteens. A sample of 4233 schoolchildren (aged 11-13 years) was recruited to assess urinary iodine concentration, prevalence of goiter, and thyroid hypoechogenicity on ultrasound, with the latter being an indirect indicator of thyroid autoimmunity. Neonatal TSH values of 197 677 infants screened in regions representative of Northern, Central, and Southern Italy were analyzed to investigate the percentage of TSH values >5.0 mIU/L. Data on methimazole prescriptions were analyzed as indirect indicators of new cases of hyperthyroidism.
RESULTS
The prevalence of the use of iodized salt was 71.5% in adult population and 78% in school canteens. A median urinary iodine concentration of 124 μg/L, a prevalence of goiter of 2.2%, and a prevalence of thyroid hypoechogenicity of 5.7% were observed in schoolchildren. The percentage of neonatal TSH values >5.0 mIU/L resulted still higher (5.1%) than the World Health Organization threshold of 3.0%, whereas the prescriptions of methimazole showed a reduction of 13.5%.
CONCLUSION
Fifteen years of iodine prophylaxis have led to iodine sufficiency in Italy, although there still is concern about iodine nutritional status during pregnancy.
Topics: Adult; Female; Infant; Pregnancy; Infant, Newborn; Humans; Child; Methimazole; Goiter; Sodium Chloride, Dietary; Iodine; Hyperthyroidism; Italy; Prevalence; Thyrotropin
PubMed: 37820735
DOI: 10.1210/clinem/dgad593 -
The Kobe Journal of Medical Sciences Feb 2021Triiodothyronine (T3)-predominant Graves' disease is characterized by increased serum free T3 (FT3) levels after free thyroxine (FT4) levels become normal or even low...
Triiodothyronine (T3)-predominant Graves' disease is characterized by increased serum free T3 (FT3) levels after free thyroxine (FT4) levels become normal or even low during antithyroid drug treatment. We encountered a 34-year-old pregnant woman, gravida 5 para 4, who was complicated by T3-predominant Graves' disease. She was diagnosed with Graves' disease at 20 years old, and had received methimazole. Methimazole was changed to potassium iodide to reduce the risk of congenital anomalies during the first trimester. The dose of antithyroid drugs was adjusted based on maternal FT4 levels, so that maternal Graves' disease deteriorated and fetal goitrous hyperthyroidism appeared during the second trimester. Since the fetus presented goiter and tachycardia at 27-28 gestational weeks, doses of methimazole and potassium iodide were increased. A male newborn weighing 2604 g was delivered by a cesarean section at 35 gestational weeks. The newborn was diagnosed with neonatal hyperthyroidism, and received methimazole for six months. He developed normally with normal thyroid function at 1 year old. In pregnancies complicated by T3-predominant Graves' disease, the kinds and doses of antithyroid drugs have to be carefully selected to maintain maternal levels of FT4 as well as FT3 within the normal range, considering trimesters of pregnancy, teratogenicity of medication, and maternal levels of thyroid-stimulating hormone receptor antibody.
Topics: Adult; Antithyroid Agents; Female; Goiter; Graves Disease; Humans; Infant, Newborn; Male; Maternal-Fetal Exchange; Methimazole; Potassium Iodide; Pregnancy; Pregnancy Complications; Pregnant Women; Thyroxine; Treatment Outcome; Triiodothyronine; Ultrasonography, Prenatal
PubMed: 33994519
DOI: No ID Found