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PloS One 2023The purpose of this meta-analysis was to assess the safety of the anti-thyroid drugs (ATDs) propylthiouracil (PTU) and methimazole (MMI) in the treatment of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this meta-analysis was to assess the safety of the anti-thyroid drugs (ATDs) propylthiouracil (PTU) and methimazole (MMI) in the treatment of hyperthyroidism during pregnancy.
METHOD
From inception until June 2, 2022, all available studies were searched in PubMed, Web of Science, Cochrane, EBSCO, Embase, Scopus, and CNKI.
RESULT
Thirteen articles satisfying the inclusion criteria were examined. Our meta-analysis indicated that pregnant women treated with MMI had a higher risk of congenital anomalies than those treated with PTU (OR 0.80, 95%CI 0.69-0.92, P = 0.002, I2 = 41.9%). Shifting between MMI and PTU during pregnancy did not reduce the risk of birth defects compared to PTU alone (OR 1.18, CI 1.00 to 1.40, P = 0.061, I2 = 0.0%). There were no statistically significant differences in hepatotoxicity (OR 1.54, 95%CI 0.77-3.09, P = 0.221, I2 = 0.0%) or miscarriage (OR 0.89, 95%CI 0.72-1.11, P = 0.310, I2 = 0.0%) between PTU and MMI exposure.
CONCLUSION
The study confirmed propylthiouracil is a safer alternative to methimazole for treating hyperthyroidism in pregnant women, and it is appropriate to treat maternal thyroid disease with PTU during the first trimester of pregnancy. However, it is not clear whether switching between propylthiouracil and methimazole is a better option than treating PTU alone during pregnancy. Further studies on this matter may be needed to develop new evidence-based guidelines for the treatment of pregnant women with hyperthyroidism.
Topics: Female; Pregnancy; Humans; Methimazole; Propylthiouracil; Antithyroid Agents; Hyperthyroidism; Abortion, Spontaneous; Pregnancy Complications
PubMed: 37205692
DOI: 10.1371/journal.pone.0286097 -
Translational Pediatrics Jan 2022Hyperthyroidism is a disease of excessive synthesis and secretion of thyroid hormones, and there is a lack of studies that have systematically evaluated the efficacy of...
BACKGROUND
Hyperthyroidism is a disease of excessive synthesis and secretion of thyroid hormones, and there is a lack of studies that have systematically evaluated the efficacy of the combination in treating hyperthyroidism. This study aimed to systematically evaluate the effectiveness and safety of methimazole combined with levothyroxine for treating hyperthyroidism in children.
METHODS
We searched PubMed, CNKI, Wanfang Database, EMBASE, Web of Science, and other online electronic databases to find correlation studies of methimazole combined with levothyroxine in treating hyperthyroidism in children from 2010 to 2021. Meta-analysis was performed using Stata 16 software.
RESULTS
Finally, 15 relevant articles were included comprising 1,718 pediatric patients. Meta-analysis results indicated that compared with methimazole alone (control group), the experimental group administered methimazole + levothyroxine had no evident difference in the level of thyroid-stimulating hormone [standardized mean difference (SMD) =-0.34, 95% confidence interval (CI): -1.02, 0.35, P=0.33], but notably improved the efficacy of clinical treatment of hyperthyroidism in children [odds ratio (OR) =5.77, 95% CI: 2.62, 12.74, P<0.001]. Meanwhile, the experimental group had lower adverse reaction rates (OR =0.28, 95%CI: 0.19, 0.40, P<0.001), free triiodothyronine (FT3) level (SMD =-0.85, 95% CI: -1.57, 0.13, P=0.02), free tetraiodothyronine (FT4) level (SMD =-0.94, 95% CI: -1.59, -0.30, P=0.004) and reduced thyroid volume (SMD =-1.3, 95% CI: -1.67, 0.93, P<0.001).
DISCUSSION
Using methimazole + levothyroxine to treat hyperthyroidism in children can raise the levels of FT3 and FT4, reduce the thyroid volume, improve clinical efficacy, and lower the adverse reaction rate of patients.
PubMed: 35242651
DOI: 10.21037/tp-21-497 -
The Cochrane Database of Systematic... Feb 2016Graves' disease is the most common cause of hyperthyroidism. Both antithyroid medications and radioiodine are commonly used treatments but their frequency of use varies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Graves' disease is the most common cause of hyperthyroidism. Both antithyroid medications and radioiodine are commonly used treatments but their frequency of use varies between regions and countries. Despite the commonness of the diagnosis, any possible differences between the two treatments with respect to long-term outcomes remain unknown.
OBJECTIVES
To assess the effects of radioiodine therapy versus antithyroid medications for Graves' disease.
SEARCH METHODS
We performed a systematic literature search in the Cochrane Library, MEDLINE and EMBASE and the trials registers ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was September 2015 for all databases.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing the effects of radioiodine therapy versus antithyroid medications for Graves' disease with at least two years follow-up.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles and abstracts for relevance. One author carried out screening for inclusion, data extraction and 'Risk of bias' assessment and a second author checked this. We presented data not suitable for meta-analysis as descriptive data. We analysed the overall quality of evidence utilising the GRADE instrument.
MAIN RESULTS
We included two RCTs involving 425 adult participants with Graves' disease in this review. Altogether 204 participants were randomised to radioiodine therapy and 221 to methimazole therapy. A single dose of radioiodine was administered. The duration of methimazole medication was 18 months. The period of follow-up was at least two years, depending on the outcome measured. For most outcome measures risk of bias was low; for the outcomes health-related quality of life as well as development and worsening of Graves' ophthalmopathy risks of performance bias and detection bias were high in at least one of the two RCTs.Health-related quality of life appeared to be similar in the radioiodine and methimazole treatment groups, however no quantitative data were reported (425 participants; 2 trials; low quality evidence). The development and worsening of Graves' ophthalmopathy was observed in 76 of 202 radioiodine-treated participants (38%) and in 40 of 215 methimazole-treated participants (19%): risk ratio (RR) 1.94 (95% confidence interval (CI) 1.40 to 2.70); 417 participants; 2 trials; low quality evidence. A total of 35% to 56% of radioiodine-treated participants and 42% of participants treated with methimazole were smokers, which is associated with the risk of worsening or development of Graves' ophthalmopathy. Euthyroidism was not achieved by any participant being treated with radioiodine compared with 64/68 (94%) of participants after methimazole treatment (112 participants; 1 trial). In this trial thyroxine therapy was not introduced early in both treatment arms to avoid hypothyroidism. Recurrence of hyperthyroidism (relapse) in favour of radioiodine treatment showed a RR of 0.20 (95% CI 0.01 to 2.66); P value = 0.22; 417 participants; 2 trials; very low quality evidence. Heterogeneity was high (I² = 91%) and the RRs were 0.61 or 0.06 with non-overlapping CIs. Adverse events other than development of worsening of Graves' ophthalmopathy for radioiodine therapy were hypothyroidism (39 of 41 participants (95%) compared with 0% of participants receiving methimazole, however thyroxine treatment to avoid hypothyroidism was not introduced early in the radioiodine group - 104 participants; 1 trial; very low quality evidence) and drug-related adverse events for methimazole treatment (23 of 215 participants (11%) reported adverse effects likely related to methimazole therapy - 215 participants; 2 trials; very low quality evidence). The outcome measures all-cause mortality and bone mineral density were not reported in the included trials. One trial (174 participants) reported socioeconomic effects: costs based on the official hospital reimbursement system in Sweden for patients without relapse and methimazole treatment were USD 1126/1164 (young/older methimazole group) and for radioiodine treatment USD 1862. Costs for patients with relapse and methimazole treatment were USD 2284/1972 (young/older methimazole group) and for radioiodine treatment USD 2760.
AUTHORS' CONCLUSIONS
The only antithyroid drug investigated in the two included trials was methimazole, which might limit the applicability of our findings with regard to other compounds such as propylthiouracil. Results from two RCTs suggest that radioiodine treatment is associated with an increased risk of Graves' ophthalmopathy. Our findings suggest some benefit from radioiodine treatment for recurrence of hyperthyroidism (relapse) but there is uncertainty about the magnitude of the effect size.
Topics: Antithyroid Agents; Graves Disease; Graves Ophthalmopathy; Humans; Iodine Radioisotopes; Methimazole; Randomized Controlled Trials as Topic; Recurrence
PubMed: 26891370
DOI: 10.1002/14651858.CD010094.pub2 -
European Journal of Cancer Prevention :... Jan 2022The thyroid peroxidase inhibiting compounds methimazole, methylthiouracil, propylthiouracil, thiouracil (i.e. 'antithyroid' drugs) and ethylenethiourea have been...
INTRODUCTION
The thyroid peroxidase inhibiting compounds methimazole, methylthiouracil, propylthiouracil, thiouracil (i.e. 'antithyroid' drugs) and ethylenethiourea have been associated to thyroid tumours in rodents. According to a systematic review by the International Agency for Research on Cancer (IARC) published in 2000, evidence for the human carcinogenicity was inadequate.
METHODS
We performed an up-to-date systematic review of human epidemiological studies on the association between such compounds and thyroid cancer incidence or mortality.
RESULTS
The literature research (1999-March 2020) identified four relevant articles. Considering also reports from the previous IARC review, this systematic review considered seven reports (five distinct studies) on antithyroid drugs and two on ethylenethiourea. As for antithyroid drugs, three reports based on different follow-ups gave results from a cohort of patients treated for hyperthyroidism in 1946-1964. In the earlier report, thyroid cancer incidence was higher in patients primarily treated with antithyroid drugs (3.2/1000) than in those originally treated with thyroidectomy (0.34/1000) or radioactive iodine (0.88/1000), which can be explained by the higher frequency of subsequent thyroidectomy, and hence the higher chance of cancer detection, in that group (30 vs. 0.5 and 1.2%). The two subsequent reports found no deaths from thyroid cancer among patients treated exclusively with antithyroid drugs through 1990 and 2014. A nested case-control study found an odds ratio (OR) of thyroid cancer of 2.79 [95% confidence interval (CI), 0.78-10.02, from a 2-year lag analysis] for ≥3 vs. no propylthiouracil prescriptions. The increased risk can be attributed to advanced diagnosis of an underlying cancer, as suggested by the stronger association observed in a no-lag analysis (OR, 8.03). In a historical cohort of newly diagnosed hyperthyroid patients, the hazard ratio for treatment with radioactive iodine vs. thionamides only was 0.45 (95% CI, 0.21-0.99), possibly due to the closer surveillance of patients receiving thionamides only. Two case-control studies did not find any association with the use of antithyroid drugs. As for ethylenethiourea, no thyroid cancer cases were found in a historical cohort of 1929 workers occupationally exposed in a 15-year period and no association with proxies of mancozeb exposure (a fungicide whose main metabolite is ethylenethiourea) was detected in a cohort of >236 000 farmers.
CONCLUSION
There is no evidence for a relevant role of either antithyroid drugs or ethylenethiourea on thyroid cancer.
Topics: Antithyroid Agents; Case-Control Studies; Ethylenethiourea; Humans; Hyperthyroidism; Iodine Radioisotopes; Propylthiouracil; Thyroid Neoplasms
PubMed: 33492873
DOI: 10.1097/CEJ.0000000000000658 -
British Journal of Clinical Pharmacology Oct 2021Maternal antithyroid drug (ATD) use during pregnancy has been associated with an increased risk of birth defects in offspring. Uncertainty remains on the size of this... (Meta-Analysis)
Meta-Analysis
Antithyroid drug use during pregnancy and the risk of birth defects in offspring: systematic review and meta-analysis of observational studies with methodological considerations.
AIMS
Maternal antithyroid drug (ATD) use during pregnancy has been associated with an increased risk of birth defects in offspring. Uncertainty remains on the size of this risk and how it compares to untreated hyperthyroidism due to methodological limitations of previous studies.
METHODS
Systematic review of MEDLINE and EMBASE identifying observational studies examining ATD use during pregnancy and risk of birth defects by 28 August 2020. Data were extracted on study characteristics, effect estimates and comparator groups. Adjusted effect estimates were pooled using a random-effects generic inverse variance method and absolute risk calculated.
RESULTS
Seven cohort studies and 1 case-control study involving 6 212 322 pregnancies and 388 976 birth defects were identified reporting regression effect estimates. Compared to an unexposed population comparison, the association between ATD use during pregnancy and birth defects in offspring was: adjusted risk ratio (aRR) 1.16 95% confidence interval (CI) 1.08-1.25 for propylthiouracil (PTU); aRR 1.28 95%CI 1.06-1.54 for methimazole/carbimazole (MMI/CMZ); aRR 1.51, 95%CI 1.16-1.97 for both MMI/CMZ and PTU; and aRR 1.15 95%CI 1.02-1.29 for untreated hyperthyroidism. The excess risk of any and major birth defects per 1000, respectively, was: 10.2 and 1.3 for PTU; 17.8 and 2.3 for MMI/CMZ; 32.5 and 4.1 for both MMI/CMZ and PTU; and 9.6 and 1.2 for untreated hyperthyroidism.
CONCLUSIONS
When appropriately analysed the risk of birth defects associated with ATD use in pregnancy is attenuated. Although still elevated, the risk of birth defects is smallest with PTU compared to MMI/CMZ and may be similar to that of untreated hyperthyroidism.
Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Case-Control Studies; Female; Humans; Hyperthyroidism; Methimazole; Observational Studies as Topic; Pregnancy; Pregnancy Complications; Propylthiouracil
PubMed: 33783857
DOI: 10.1111/bcp.14805 -
Sao Paulo Medical Journal = Revista... 2023The efficacy of anti-thyroid drugs in conjunction with radioactive iodine therapy in the management of Graves' disease is still controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of anti-thyroid drugs in conjunction with radioactive iodine therapy in the management of Graves' disease is still controversial.
OBJECTIVE
To compare the efficacy of pretreatment with methimazole before the administration of radioactive iodine for the treatment of Graves' disease.
DESIGN AND SETTING
A systematic review and meta-analysis was conducted at a teaching/tertiary hospital in Ibadan, Nigeria.
METHODS
A systematic search of the PubMed, Embase, Cochrane Library, and Web of Science databases was performed from inception to December, 2021.
RESULTS
Five studies with 297 participants were included. There was no difference in the risk of persistent hyperthyroidism when radioactive iodine was used in conjunction with methimazole compared with when radioactive iodine was used alone (relative risk: 1.02, 95% confidence interval, CI: 0.62-1.66; P = 0.95, I2 = 0%). Subgroup analysis based on the duration between discontinuation of methimazole and the administration of radioactive iodine showed a lower risk of persistent hyperthyroidism when methimazole was discontinued within 7 days before radioactive iodine use, although this did not reach statistical significance (risk ratio: 0.85, CI: 0.28-2.58).
CONCLUSIONS
The use of methimazole before radioactive iodine administration was not associated with an increased risk of persistent hyperthyroidism. Concerns about medication toxicity and adverse effects should be considered when clinicians make decisions on combination therapies for the treatment of Graves' disease.
PROSPERO REGISTRATION
CRD42020150013, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150013.
Topics: Humans; Methimazole; Antithyroid Agents; Iodine Radioisotopes; Nigeria; Thyroid Neoplasms; Graves Disease; Hyperthyroidism
PubMed: 36629663
DOI: 10.1590/1516-3180.2022.0225.R1.19102022 -
Medicine Sep 2020Hyperthyroidism is a condition in which the thyroid gland is overreactive and produces excess amounts of thyroid hormone. Tripterygium glycosides, traditional Chinese... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hyperthyroidism is a condition in which the thyroid gland is overreactive and produces excess amounts of thyroid hormone. Tripterygium glycosides, traditional Chinese medicine has been widely used in the treatment of rheumatoid arthritis, nephrotic syndrome, hyperthyroidism and other diseases due to its anti-inflammatory and immunosuppressive effects. Evidence-based research is becoming popular especially with the application of Chinese traditional medicine. This paper systematically reviews and evaluates existing clinical data on the efficacy and safety of Tripterygium glycosides in the treatment of hyperthyroidism.
MATERIALS AND METHODS
PubMed, Cochrane library and EMBase, Chinese biomedical literature database (CBM), Chinese journal full-text database (CNKI), Wan fang digital periodical full-text database and China Science and Technology Journal Database (VIP) were searched based on the defined inclusion and exclusion criteria. Data extraction, research quality assessment and meta-analysis were conducted with RevMan5.3 software. Trial sequential analysis (TSA) was used to evaluate information size and treatment benefits.
RESULTS
Seventeen randomized controlled clinical trials with 1536 participants were included in the systematic review. In the meta-analysis, there were two subgroups: Tripterygium glycosides combined with thiamazole and prednisone group; Tripterygium glycosides combined with thiamazole group. The study results revealed that the degree of exophthalmos, FT3, FT4, BGP, and AKP decreased while TSH, SOD, GSH-PX increased after the addition of Tripterygium glycosides. This study results suggested that Tripterygium glycosides combined with western medicine are an effective therapy for hyperthyroidism.
CONCLUSION
This study indicates that Tripterygium glycosides enhances the effect of thiamazole and prednisone in the treatment of hyperthyroidism and without increasing the risk of adverse events.
Topics: Anti-Inflammatory Agents; Drug Therapy, Combination; Drugs, Chinese Herbal; Glycosides; Humans; Hyperthyroidism; Methimazole; Prednisone; Tripterygium
PubMed: 32957384
DOI: 10.1097/MD.0000000000022282 -
Cureus May 2024Graves' disease (GD) is an autoimmune condition of the thyroid. The hyperthyroidism manifested by patients affected by this disease is caused by the production of... (Review)
Review
Graves' disease (GD) is an autoimmune condition of the thyroid. The hyperthyroidism manifested by patients affected by this disease is caused by the production of autoantibodies against the thyroid-stimulating hormone (TSH, or thyrotropin) receptor (TSHR), which mimic the effects of the hormone on thyroid cells, thereby stimulating autonomic production of thyroxine and triiodothyronine. Deciding on a therapeutic approach to this condition presents intricate dilemmas for both clinicians and patients. Each of the three available treatment modalities is grounded in evidence-based medicine, affirming its efficacy. This systematic review and meta-analysis aimed to assess the effect of carbimazole (CBM), radioactive iodine (RAI), and surgery in treating GD and provide evidence-based recommendations for healthcare providers regarding the optimal management of the condition based on a comprehensive analysis of effectiveness, safety, patient satisfaction, and recovery outcomes. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used the PubMed and Google Scholar databases to conduct a thorough web search for articles published between January 2019 and September 2023. The meta-analysis was carried out using Resource Manager (Revman) 5.4.1. The study found that propylthiouracil (PTU) or methimazole/carbimazole (MMI/CBM) treatment increases the risk of hyperlipidemia in patients with hyperthyroidism. Once in a euthyroid state, glucose tolerance increases; for children with GD, a computer model for customized dosing has been created. To sum up, CBM, surgery, and RAI are all useful treatment options for GD. Using steroids in conjunction with radiation therapy may help prevent Graves' ophthalmopathy (GO).
PubMed: 38910658
DOI: 10.7759/cureus.60829 -
Frontiers in Endocrinology 2023The authors aimed to investigate the clinical characteristics of antithyroid drug-induced aplastic anemia cases over the past 30 years.
OBJECTIVE
The authors aimed to investigate the clinical characteristics of antithyroid drug-induced aplastic anemia cases over the past 30 years.
METHODS
The data of patients with antithyroid drug-induced aplastic anemia were retrieved from PubMed and Wanfang Medical Network databases from 1992 to August 2022. The clinical characteristics, such as age distribution, gender tendency, common symptoms, blood cell count, bone marrow features, treatment strategy, and prognosis, were analyzed.
RESULTS
A total of 17 cases (male:female = 1:16) had been retrieved. Patients' age ranged from 16 to 74 years (median 50 years). Among them, 82.3% (14/17) of the patients were administered methimazole (MMI), and 78.6% of them had MMI ≥30 mg/day. In addition, 88.2% (15/17) of the patients had sore throat and fever, and 47.1% (8/17) of the patients had hemorrhagic symptoms. Aplastic anemia occurred within 6 months after initiation of the antithyroid therapy in 94.1% of the patients. Agranulocytosis (94.1%) was the most common and earliest blood cell change, and 47.1% of the patients experienced progressive platelet decline during the treatment process. The treatments include timely withdrawal of antithyroid drugs, broad-spectrum antibiotics, granulocyte colony-stimulating factor (G-CSF)/granulocyte-macrophage colony-stimulating factor (GM-CSF), glucocorticoids and other immunosuppressive agents, and supportive treatments such as erythrocyte transfusion and platelet transfusion. Moreover, 70.6% of the patients had complete or near-complete remission within 8 days to 6 weeks.
CONCLUSION
Aplastic anemia is a rare and serious adverse reaction of antithyroid drugs, which is more common in women. It usually occurs during early treatment with high-dose antithyroid drugs. Most patients have a good prognosis after timely drug ceasing and appropriate treatment.
Topics: Female; Humans; Male; Adolescent; Young Adult; Adult; Middle Aged; Aged; Antithyroid Agents; Anemia, Aplastic; Methimazole; Bone Marrow; Glucocorticoids
PubMed: 36777352
DOI: 10.3389/fendo.2023.1064723 -
BMC Endocrine Disorders May 2019Simultaneous development of thyroid storm and diabetic ketoacidosis (DKA) is a rare condition. The review aims to summarise its clinical presentation, investigation...
BACKGROUND
Simultaneous development of thyroid storm and diabetic ketoacidosis (DKA) is a rare condition. The review aims to summarise its clinical presentation, investigation findings and treatment options.
METHODS
Databases and reference lists of the selected articles were searched for case reports in English which describe concurrent presentation of thyroid storm and diabetic ketoacidosis. CARE guidelines were used for the quality assessment of the selected articles.
RESULTS
Twenty-six cases from twenty-one articles were selected out of 198 search results. Western Pacific, and American regions contributed to 77% of the cases. Females were most affected (88%). Features of Graves' disease like hyperthermia and tachycardia, gastrointestinal and neuro-psychiatric disturbances were the common clinical presentations. In most of the cases, previous diagnosis of diabetes mellitus preceded that of Graves' disease (46%). Among patients having their drug compliance reported, all had poor compliance to their routine anti-thyroid (9/9) and anti-diabetic (2/2) agents. Moreover, in all cases where HbA (7/7) and T4 (16/16) were measured, the results were elevated and where TSH (17/17) was measured, the results were low. The recommended treatment for DKA and thyroid storm was used in most cases and methimazole was the thionamide of choice in the latest four cases reported. All cases survived except four (15%).
CONCLUSIONS
Concurrent presentation of thyroid storm and diabetic ketoacidosis is rare but life-threatening. Therefore, efforts should be made to maximise patient compliance to anti-thyroid and anti-diabetic agents in treating such patients.
Topics: Diabetic Ketoacidosis; Humans; Meta-Analysis as Topic; Prognosis; Thyroid Crisis
PubMed: 31101104
DOI: 10.1186/s12902-019-0374-3