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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 -
BMJ Clinical Evidence Jul 2010Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of... (Review)
Review
INTRODUCTION
Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma. About 20 times more women than men have hyperthyroidism.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for primary hyperthyroidism? What are the effects of surgical treatments for primary hyperthyroidism? What are the effects of treatments for subclinical hyperthyroidism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding thyroxine to antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), radioactive iodine, and thyroidectomy.
Topics: Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Incidence; Methimazole; Thyrotropin
PubMed: 21418670
DOI: No ID Found -
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 -
BMJ Clinical Evidence Mar 2008Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of... (Review)
Review
INTRODUCTION
Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism are Graves' disease, toxic multinodular goitre, and toxic adenoma. About 20 times more women than men have hyperthyroidism.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for primary hyperthyroidism? What are the effects of surgical treatments for primary hyperthyroidism? What are the effects of treatments for subclinical hyperthyroidism? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding thyroxine to antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), radioactive iodine, and thyroidectomy.
Topics: Antithyroid Agents; Graves Disease; Humans; Hyperthyroidism; Incidence; Methimazole; Thyrotropin
PubMed: 19450325
DOI: No ID Found -
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 -
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 -
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 -
The Cochrane Database of Systematic... Sep 2010Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe... (Review)
Review
BACKGROUND
Women with hyperthyroidism in pregnancy have increased risks of miscarriage, stillbirth, preterm birth, and intrauterine growth restriction; and they can develop severe pre-eclampsia or placental abruption.
OBJECTIVES
To assess the effects of interventions for preventing or treating hyperthyroidism in pregnant women.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 July 2010).
SELECTION CRITERIA
We intended to include randomised controlled trials comparing antithyroid treatments in pregnant women with hyperthyroidism.
DATA COLLECTION AND ANALYSIS
Two review authors would have assessed trial eligibility and risk of bias, and extracted data.
MAIN RESULTS
No trials were located.
AUTHORS' CONCLUSIONS
As we did not identify any eligible trials, we are unable to comment on implications for practice, although early identification of hyperthyroidism before pregnancy may allow a woman to choose radioactive iodine therapy or surgery before planning to have a child. Designing and conducting a trial of antithyroid drugs for pregnant women with hyperthyroidism presents formidable challenges. Not only is hyperthyroidism a relatively rare condition, both of the two main drugs used have potential for harm, one for the mother and the other for the child. More observational research is required about the potential harms of methimazole in early pregnancy and about the potential liver damage from propylthiouracil.
Topics: Female; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications; Randomized Controlled Trials as Topic
PubMed: 20824882
DOI: 10.1002/14651858.CD008633.pub2 -
The Journal of Clinical Endocrinology... Sep 2013Several treatment options are available for Graves' disease (GD), including antithyroid drugs (ATDs), radioactive iodine (RAI), and thyroidectomy. (Comparative Study)
Comparative Study Meta-Analysis Review
CONTEXT
Several treatment options are available for Graves' disease (GD), including antithyroid drugs (ATDs), radioactive iodine (RAI), and thyroidectomy.
OBJECTIVE
The primary outcome was to determine the relapse rates of various treatment options. The secondary outcome was to present data regarding adverse effects of ATDs.
DATA SOURCES
We searched multiple databases through March 2012.
STUDY SELECTION
Eligible studies were randomized clinical trials and comparative cohort studies in adults that included 2 or more treatment options for GD.
DATA EXTRACTION
Two reviewers independently selected studies, appraised study quality, extracted outcome data, and determined adverse effect profiles.
DATA SYNTHESIS
We found 8 studies with 1402 patients from 5 continents. Mean follow-up duration in months was: ATDs, 57; RAI, 64; and surgery, 59. Studies were at moderate to high risk of bias. Network meta-analysis suggested higher relapse rates with ATDs (52.7%; 352 of 667) than RAI (15%, 46 of 304) (odds ratio = 6.25; 95% confidence interval, 2.40-16.67) and with ATDs than surgery (10%; 39 of 387) (odds ratio = 9.09; 95% confidence interval, 4.65-19.23). There was no significant difference in relapse between RAI and surgery. Examination of 31 cohort studies identified adverse effects of ATDs in 692 of 5136 (13%) patients. These were more common with methimazole, mainly owing to dermatological complications, whereas hepatic effects were more common with propylthiouracil use.
CONCLUSION
We confirm the relatively high relapse rate of ATD therapy in comparison with RAI or surgery, along with a significant side effect profile for these drugs. These data can inform discussion between physicians and patients regarding the choice of therapy for GD. The limited quality of the evidence in the literature underlines the need for future randomized clinical trials in this area.
Topics: Antithyroid Agents; Databases, Factual; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Recurrence; Thyroidectomy; Treatment Outcome
PubMed: 23824415
DOI: 10.1210/jc.2013-1954