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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 -
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 -
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 -
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 -
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 -
Clinical Pharmacology and Therapeutics May 2016Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is...
Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.
Topics: Agranulocytosis; Antithyroid Agents; Carbimazole; Case-Control Studies; Female; Genome-Wide Association Study; HLA-B Antigens; Humans; Linkage Disequilibrium; Methimazole; Polymorphism, Single Nucleotide; Predictive Value of Tests; Propylthiouracil
PubMed: 26599303
DOI: 10.1002/cpt.309 -
Endocrinology and Metabolism (Seoul,... Dec 2022An excess of thyroid hormones in Graves' disease (GD) has profound effects on systemic energy metabolism that are currently partially understood. In this study, we aimed...
BACKGRUOUND
An excess of thyroid hormones in Graves' disease (GD) has profound effects on systemic energy metabolism that are currently partially understood. In this study, we aimed to provide a comprehensive understanding of the metabolite changes that occur when patients with GD transition from hyperthyroidism to euthyroidism with methimazole treatment.
METHODS
Eighteen patients (mean age, 38.6±14.7 years; 66.7% female) with newly diagnosed or relapsed GD attending the endocrinology outpatient clinics in a single institution were recruited between January 2019 and July 2020. All subjects were treated with methimazole to achieve euthyroidism. We explored metabolomics by performing liquid chromatography-mass spectrometry analysis of plasma samples of these patients and then performed multivariate statistical analysis of the metabolomics data.
RESULTS
Two hundred metabolites were measured before and after 12 weeks of methimazole treatment in patients with GD. The levels of 61 metabolites, including palmitic acid (C16:0) and oleic acid (C18:1), were elevated in methimazole-naïve patients with GD, and these levels were decreased by methimazole treatment. The levels of another 15 metabolites, including glycine and creatinine, were increased after recovery of euthyroidism upon methimazole treatment in patients with GD. Pathway analysis of metabolomics data showed that hyperthyroidism was closely related to aminoacyl-transfer ribonucleic acid biosynthesis and branched-chain amino acid biosynthesis pathways.
CONCLUSION
In this study, significant variations of plasma metabolomic patterns that occur during the transition from hyperthyroidism to euthyroidism were detected in patients with GD via untargeted metabolomics analysis.
Topics: Humans; Female; Young Adult; Adult; Middle Aged; Male; Methimazole; Antithyroid Agents; Hyperthyroidism; Graves Disease; Thyroid Hormones
PubMed: 36604959
DOI: 10.3803/EnM.2022.1590 -
The American Journal of Case Reports Sep 2020BACKGROUND Methimazole embryopathy is caused by maternal methimazole intake during early pregnancy. It causes fetal malformations such as choanal atresia, esophageal...
BACKGROUND Methimazole embryopathy is caused by maternal methimazole intake during early pregnancy. It causes fetal malformations such as choanal atresia, esophageal atresia, aplasia cutis, omphalomesenteric duct remnants, urachal remnants, and omphalocele. Gallbladder agenesis is sometimes complicated with other malformations, but there have been no reports of gallbladder agenesis due to methimazole or concomitant methimazole embryopathy with gallbladder agenesis. CASE REPORT The mother of a male neonate had taken methimazole for hyperthyroidism until pregnancy was recognized at 7 weeks of gestation. Ultrasonography at 12 weeks and 4 days of gestation showed the fetus had a cystic lesion in the umbilical region. The child was born at the gestational age of 38 weeks and 5 days. At birth there was omphalocele, omphalomesenteric fistula, and a scalp defect, and the child was diagnosed with methimazole embryopathy. Ultrasonography could not identify the gallbladder. Emergency surgery was performed for omphalocele with omphalomesenteric fistula on day 0. The intestine, including the omphalomesenteric fistula, was resected. Postoperative blood testing revealed hypothyroidism, so the patient was administered levothyroxine. Although MRI did not detect the gallbladder, it showed dilatation of the biliary duct. Hypothyroidism was well controlled by levothyroxine, so the patient was discharged with outpatient follow-up for the gallbladder agenesis. Six months later, the patient is asymptomatic. CONCLUSIONS Concomitant gallbladder agenesis with methimazole embryopathy has not been previously reported. In the case of a dilated common bile duct, even when asymptomatic in the neonatal period, gallbladder agenesis demands long-term follow-up because of possible manifestation of choledocholithiasis or biliary malignant tumors.
Topics: Antithyroid Agents; Child; Female; Fetal Diseases; Gallbladder; Humans; Hyperthyroidism; Infant; Infant, Newborn; Male; Methimazole; Pregnancy
PubMed: 32898128
DOI: 10.12659/AJCR.926310 -
BMC Endocrine Disorders Oct 2023This study aimed to evaluate the association between the initial dose of MMI and the clinical course, as well as adverse effects on young people with GD.
OBJECTIVE
This study aimed to evaluate the association between the initial dose of MMI and the clinical course, as well as adverse effects on young people with GD.
METHODS
One hundred and sixty-one children and adolescents with newly diagnosed GD were enrolled for this study and categorized into four groups based on initial serum-free T3 and T4 levels and daily MMI doses: Group A (mild, 0.3-0.5 mg/kg/day, n = 78), Group B (moderate, 0.6-0.8 mg/kg/day, n = 37), Group C (severe, 0.6-0.8 mg/kg/day, n = 24), and Group D (severe, 0.8-1.0 mg/kg/day, n = 22). The thyroid function, blood cell analysis and liver function were examined before treatment and at 4, 8 and 12 weeks after treatment. Outcome of long-term follow-up were also observed.
RESULTS
After 12 weeks of treatment, 91.0% of the patients in group A and 90.9% of the patients in group D recovered to normalization of FT3, which was slightly higher than the other two groups; 70.8% of the patients in group C recovered to normalization of FT4, which was slightly lower than that in the other three groups. The incidence of minor adverse effects was 12.8% in group A, 13.5% in group B, 16.7% in group C and 40.9% in group D (P < 0.01). Remission was achieved in 38 patients (23.6%).
CONCLUSIONS
Lower doses of MMI (0.3-0.5 mg/kg/day) are suitable for mild GD, and higher doses of MMI (0.6-0.8 mg/kg/day) are advisable for moderate or severe GD. Much higher doses of MMI (0.8-1.0 mg/kg/day) are harmful for initial use in children and adolescents with GD patients.
Topics: Humans; Adolescent; Child; Methimazole; Antithyroid Agents; Outpatients; Thyroxine; Graves Disease
PubMed: 37872592
DOI: 10.1186/s12902-023-01484-2 -
Theoretical Biology & Medical Modelling Jan 2018Graves' is disease an autoimmune disorder of the thyroid gland caused by circulating anti-thyroid receptor antibodies (TRAb) in the serum. TRAb mimics the action of...
BACKGROUND
Graves' is disease an autoimmune disorder of the thyroid gland caused by circulating anti-thyroid receptor antibodies (TRAb) in the serum. TRAb mimics the action of thyroid stimulating hormone (TSH) and stimulates the thyroid hormone receptor (TSHR), which results in hyperthyroidism (overactive thyroid gland) and goiter. Methimazole (MMI) is used for hyperthyroidism treatment for patients with Graves' disease.
METHODS
We have developed a model using a system of ordinary differential equations for hyperthyroidism treatment with MMI. The model has four state variables, namely concentration of MMI (in mg/L), concentration of free thyroxine - FT4 (in pg/mL), and concentration of TRAb (in U/mL) and the functional size of the thyroid gland (in mL) with thirteen parameters. With a treatment parameter, we simulate the time-course of patients' progression from hyperthyroidism to euthyroidism (normal condition). We validated the model predictions with data from four patients.
RESULTS
When there is no MMI treatment, there is a unique asymptotically stable hyperthyroid state. After the initiation of MMI treatment, the hyperthyroid state moves towards subclinical hyperthyroidism and then euthyroidism.
CONCLUSION
We can use the model to describe or test and predict patient treatment schedules. More specifically, we can fit the model to individual patients' data including loading and maintenance doses and describe the mechanism, hyperthyroidism→euthyroidism. The model can be used to predict when to discontinue the treatment based on FT4 levels within the physiological range, which in turn help maintain the remittance of euthyroidism and avoid relapses of hyperthyroidism. Basically, the model can guide with decision-making on oral intake of MMI based on FT4 levels.
Topics: Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Methimazole; Models, Biological; Thyroid Gland; Thyrotropin; Thyroxine; Treatment Outcome
PubMed: 29310665
DOI: 10.1186/s12976-017-0073-6