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AACE Clinical Case Reports 2021To describe a 4-year-old girl with Graves disease and methimazole allergy who underwent desensitization, allowing continued methimazole use when other treatments were...
OBJECTIVE
To describe a 4-year-old girl with Graves disease and methimazole allergy who underwent desensitization, allowing continued methimazole use when other treatments were contraindicated.
METHODS
We formulated a desensitization plan utilizing cetirizine and prednisone for a patient with previously diagnosed Graves disease who developed urticaria and arthralgias from methimazole. She was admitted for monitoring of rash, urticaria, angioedema, and anaphylaxis. Her methimazole dose was increased as tolerated and then titrated as an outpatient.
RESULTS
A 4-year-old girl presented with a heart rate of 195 beats/minute, blood pressure of 145/108, and subsequent labs of undetectable thyroid stimulating hormone (TSH), free T4 5.8 ng/dL, thyroid peroxidase antibody 11.5 IU/ml, and TSH receptor antibody 39.03 IU/L, consistent with Graves disease. She developed urticaria and arthralgias after 2.5 weeks on methimazole, which resolved with drug cessation. Because of her age, the risks of radioactive iodine ablation and surgery were concerning; therefore, methimazole desensitization was attempted. Prednisone (1 mg/kg/day) and cetirizine (5 mg/day) were started prior to low-dose methimazole reintroduction and continued for 7 days. Methimazole was then gradually increased to a final dose of 15 mg daily (0.8 mg/kg/day). Free T4 normalized within a month (1.12 ng/dL), and her TSH normalized within 10 months (4.61 mcU/mL). Except for 2 possible breakthrough allergic responses that resolved with pulse steroids, she continues to tolerate methimazole.
CONCLUSION
We describe a case of methimazole desensitization. In this patient, pretreatment with prednisone, coupled with daily cetirizine, successfully induced methimazole tolerance when other treatment modalities were contraindicated.
PubMed: 34307852
DOI: 10.1016/j.aace.2021.02.002 -
European Thyroid Journal May 2022In this prospective multicenter study with patients newly diagnosed with Graves' hyperthyroidism (GH), we studied the timing and characteristics of adverse drug...
PURPOSE
In this prospective multicenter study with patients newly diagnosed with Graves' hyperthyroidism (GH), we studied the timing and characteristics of adverse drug reactions in patients treated with anti-thyroid drugs (ATD) for up to 48 months.
METHODS
Patients with GH were treated with ATD until remission and hereafter with a low-dose regime to keep the patients in remission. The patients were followed with blood samples and recording of adverse events approximately every second month for the first 2 years and every third month for the following 2 years.
RESULTS
We included 208 patients and the patients were treated for a median of 22 (range: 0.5-49) months. Ten percent of the patients experienced adverse drug reactions and 75% of the cases occurred during the first 6 months. After 24 months, the methimazole dose was lowered to 5 mg/day, and after this time point, no further adverse drug reactions were recorded. Skin reactions were the most prominent reaction, comprising 68% of the registered reactions, and no hepatic and bonemarrow affection was recorded.
CONCLUSION
With this study, we report the frequency, timing of occurrence, and characteristics of adverse drug reactions when treating GH with the ATD drug methimazole for up to 48 months. Long-term low-dose methimazole treatment can be a cost-effective and straightforward treatment option if adverse drug reactions such as severe hepatic and bone marrow affection are kept in mind.
PubMed: 35521775
DOI: 10.1530/ETJ-22-0031 -
Frontiers in Endocrinology 2021Hyperthyroidism is related to vascular atherosclerosis. Propylthiouracil (PTU) and methimazole, other than their antithyroid effects, may have different mechanisms in... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Hyperthyroidism is related to vascular atherosclerosis. Propylthiouracil (PTU) and methimazole, other than their antithyroid effects, may have different mechanisms in preventing atherogenesis in Graves' disease.
OBJECTIVE
This study aimed to investigate the effect of antithyroid drugs on markers of vascular atherosclerosis in Graves' hyperthyroidism.
METHODS
This study was a single-blind, randomized clinical trial conducted on 36 patients with Graves' disease in Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, from June 2019 until July 2020. Graves' disease was diagnosed from clinical manifestation of hyperthyroidism with diffuse goiter and then confirmed by thyroid stimulation hormone (TSH), free T4 (fT4), and TSH-receptor antibody (TRAb) measurements. Participants were randomly assigned to either a PTU or a methimazole treatment group and followed up for 3 months. Markers of vascular atherosclerosis were represented by adhesion molecules [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin], carotid artery stiffness [pulse wave velocity (PWV)], and thickness [carotid intima media thickness (cIMT)].
RESULTS
By the end of the study, 24 participants reached euthyroid condition (13 from the PTU group and 11 from the methimazole group). After 3 months of follow-up, in the PTU group, we noticed an improvement of ICAM-1 [pretreatment: 204.1 (61.3) vs. posttreatment: 141.6 (58.4) ng/ml; p = 0.001], VCAM-1 [837 (707-977) vs. 510 (402-630) ng/ml; p < 0.001] and E-selectin [32.1 (24.1-42.7) vs. 28.2 (21.6-36.8) ng/ml; p = 0.045] in the PTU group. In the methimazole group, only VCAM-1 improvement [725 (565-904) vs. 472 (367-590); p = 0.001] was observed. Meanwhile, we found no significant changes in PWV or cIMT in either group.
CONCLUSION
Antithyroid treatment in Graves' disease leads to improvement in adhesion molecules, with a lesser effect on methimazole, whereas there were no significant changes in PWV or cIMT. PTU may have a better mechanism compared with methimazole in terms of improving adhesion molecules.
Topics: Adult; Antithyroid Agents; Atherosclerosis; Biomarkers; Female; Follow-Up Studies; Graves Disease; Humans; Intercellular Adhesion Molecule-1; Male; Methimazole; Middle Aged; Propylthiouracil; Pulse Wave Analysis; Single-Blind Method; Thyroid Hormones; Treatment Outcome; Vascular Cell Adhesion Molecule-1
PubMed: 34987480
DOI: 10.3389/fendo.2021.796194 -
Annals of Pediatric Endocrinology &... Sep 2021The first-line antithyroid drug for children and adolescents with Graves' disease (GD) is methimazole (MMI). This study evaluated the relationship between the initial...
PURPOSE
The first-line antithyroid drug for children and adolescents with Graves' disease (GD) is methimazole (MMI). This study evaluated the relationship between the initial MMI dose and the clinical course of GD after treatment.
METHODS
We studied the efficacy of the initial MMI dose and the relationship between the initial MMI dose and adverse events (AEs). We retrospectively enrolled 22 males and 77 females and divided those subjects into 3 groups according to the initial dose of MMI: <0.4 mg/kg/day (group A; n=32); 0.4-0.7 mg/kg/day (group B; n=39); and >0.7 mg/kg/day (group C; n=28).
RESULTS
The mean time to the normalization of free thyroxine (fT4) levels upon initial treatment was 5.64, 8.61, and 7.98 weeks in groups A, B, and C, respectively (P=0.116). The incidence of liver dysfunction, neutropenia, and skin rash was 12.5%, 20.5%, and 42.9% in groups A, B, and C, respectively (P=0.018). Neutropenia, as a severe AE, was absent in group A, but its prevalence was 7.7% in group B and 21.4% in group C (P=0.015). When comparing only groups B and C, the incidences of liver dysfunction and neutropenia were higher in group C (P=0.04 and P=0.021, respectively).
CONCLUSION
The mean time to the normalization of fT4 levels did not differ among the 3 groups, but the incidence of AEs was higher in the groups that received high MMI doses. High doses of MMI (>0.7 mg/kg/day) should be reconsidered as an initial treatment for children and adolescents with GD.
PubMed: 34610704
DOI: 10.6065/apem.2142046.023 -
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 -
Journal of Veterinary Research Mar 2019Thyroid hormones play a major role in the regulation of testicular maturation and growth and in the control of Sertoli and Leydig cell functions in adulthood. When...
INTRODUCTION
Thyroid hormones play a major role in the regulation of testicular maturation and growth and in the control of Sertoli and Leydig cell functions in adulthood. When naturally occurring, hypothyroidism causes male hypogonadotropic hypogonadism and Sertoli cell function disorders, but when iatrogenic and methimazole-induced its influence on the pituitary-testicular axis function with respect to Sertoli cells is poorly known.
MATERIAL AND METHODS
Male adult Wistar rats (n = 14) were divided into two groups: E - taking methimazole orally for 60 days, and C - control animals. After 60 d, the concentrations in serum of testosterone, follicle-stimulating and luteinising hormones, and inhibins A and B were measured. Testicles were examined morphologically: the apoptotic Sertoli cell percentage (ASC%) and number of these cells functional per tubular mm (FSCN/Tmm) were calculated.
RESULTS
In group E, inhibin A was higher while inhibin B was lower than in group C. ASC% was higher and FSCN/Tmm lower in group E than in group C.
CONCLUSION
A specific modulation of Sertoli cell function in the course of methimazole-induced hypothyroidism leads to a simultaneous concentration increase in inhibin A and decrease in B. Inhibin A might share responsibility for pituitary-testicular axis dysfunction and hypogonadotropic hypogonadism in this model of hypothyroidism.
PubMed: 30989148
DOI: 10.2478/jvetres-2019-0008 -
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 -
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 -
Physiological Reports Apr 2024Thyroid hormones regulate metabolic rate, nutrient utilization, growth, and development. Swine are susceptible to thyroid suppression in response to disease or...
Thyroid hormones regulate metabolic rate, nutrient utilization, growth, and development. Swine are susceptible to thyroid suppression in response to disease or environmental conditions, but the physiological impact of such disruption has not been established. The objective of this study was to evaluate the impact of hypothyroidism induced with the antithyroid medication methimazole (MMI). 10 mg/kg MMI significantly decreased circulating triiodothyronine (T3) for the duration of treatment but had only a transient effect on circulating thyroxine (T4). Thyroid tissue weight was significantly increased by more than 3.5-fold in response to MMI treatment. Histologically, the eosinophilic colloid was largely absent from the thyroid follicle which displayed a disorganized columnar epithelium consistent with goiter. MMI induced hypothyroidism has no effect on growth rate over 28 days. Hepatic expression of genes associated with thyroid metabolism (DIO1, DIO2, and DIO3), lipid utilization (CD36, FASN, and ACACA), apoptosis (TP53, PERP, SIVA1, and SFN) and proliferation (CDK1, CDK2, CDK4, and CDKN1A) were unaffected by treatment. Collectively these results demonstrate that MMI induces mild systemic hypothyroidism and pronounced goiter, indicating a strong homeostatic central regulation within the hypothalamic pituitary thyroid axis. This combined with limited peripheral effects, indicates resilience to hypothyroidism in modern swine.
Topics: Animals; Methimazole; Hypothyroidism; Swine; Antithyroid Agents; Thyroid Gland; Female; Triiodothyronine; Liver; Thyroxine; Male
PubMed: 38658325
DOI: 10.14814/phy2.16007 -
Antioxidants (Basel, Switzerland) Sep 2021Feline hyperthyroidism is a clinical syndrome related to an excessive production of thyroid hormones, and it is considered as a spontaneous animal model for human... (Review)
Review
Feline hyperthyroidism is a clinical syndrome related to an excessive production of thyroid hormones, and it is considered as a spontaneous animal model for human thyrotoxicosis. Many shared features between the feline and the human disease have been identified so far, including pathogenesis, clinical signs, and treatment options. Although methimazole is considered the first-choice drug in both species, several side effects have been described. Furthermore, methimazole could interfere with the oxidative status, already perturbated by the disease. It has been reported in humans that dietary management, mainly through antioxidant supplementation, could mitigate this oxidative burden. The purpose of the review is to describe current therapeutic options in the course of feline hyperthyroidism and to summarize the state of the art relationship between dietary antioxidants administration and the reduction of methimazole side-effects in humans to support the use of this approach also in cats.
PubMed: 34573128
DOI: 10.3390/antiox10091496