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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 -
Endocrine Practice : Official Journal... Feb 2020The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating... (Meta-Analysis)
Meta-Analysis
The present study aimed to investigate the adverse effects of the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI)/carbimazole (CMZ) in treating hyperthyroidism. Qualitative analysis was performed for studies identified in a literature search up to April 20, 2019, and 30 studies were selected for meta-analysis. The study designs included case-control, randomized controlled, and retrospective cohort. Patients were in four age groups: childhood, gestating mothers, older adults, and other ages, and all were receiving PTU or MMI/CMZ. Adverse reactions to MMI/CMZ and PTU were evaluated and compared. Odds of liver function injury were higher in the PTU group than in the MMI/CMZ group (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.16 to 4.96; = .02). Odds of elevated transaminase were much higher in the PTU group than in the MMI/CMZ group (OR, 3.96; 95% CI, 2.49 to 6.28; <.00001). No significant between-group differences were found in odds of elevated bilirubin, agranulocytosis, rash, or urticaria; incidence of other adverse events; or in children. Odds of birth defects during the first trimester of pregnancy were higher in the MMI/CMZ group than in the PTU group (OR, 1.29; 95% CI, 1.09 to 1.53; = .003). The impact of PTU on liver injury and transaminase levels is greater than that of MMI/CMZ, but no significant between-group differences are found in the drugs' effects on bilirubin, agranulocytosis and rash, urticaria, or in children. In treating pregnancy-related hyperthyroidism, PTU should be used in the first trimester and MMI reserved for use in late pregnancy. = alanine aminotransferase; = antithyroid drug; = confidence interval; = carbimazole; = Graves disease; = methimazole; = methylthiouracil; = Newcastle-Ottawa Scale; = odds ratio; = propylthiouracil; = radioactive iodine.
Topics: Aged; Antithyroid Agents; Child; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Propylthiouracil; Retrospective Studies; Thyroid Neoplasms
PubMed: 31652102
DOI: 10.4158/EP-2019-0221 -
BMJ Clinical Evidence Jan 2015Hyperthyroidism 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 in pregnancy are Graves' disease and chorionic gonadotrophin (hCG)-mediated hyperthyroidism.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of antithyroid drug treatments for hyperthyroidism in pregnancy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2014 (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 no 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: antithyroid drugs (carbimazole/thiamazole and propylthiouracil).
Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Pregnancy; Pregnancy Complications
PubMed: 25614153
DOI: No ID Found -
Thyroid : Official Journal of the... Oct 2017Several studies have reported inconsistent findings on the advantages and disadvantages of long-term treatment with antithyroid drugs (ATD). A systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several studies have reported inconsistent findings on the advantages and disadvantages of long-term treatment with antithyroid drugs (ATD). A systematic review and meta-analysis was undertaken to clarify the numerous aspects of long-term treatment with ATD.
METHODS
Medline and the Cochrane Library for trials published between 1950 and May 2016 were systematically searched. Studies containing data for long-term (>24 months) ATD treatment were included. Summary estimates of pooled prevalence, odds ratio, and weighted mean difference were calculated with a random effects model.
RESULTS
Of 587 related articles found, six fulfilled the inclusion criteria. Long-term ATD treatment induced a remission rate of 57% [confidence interval (CI) 45-68%], a rate that was higher in adults than in non-adults (61% vs. 53%). The rate of complications was 19.1% [CI 9.6-30.9%], of which only 1.5% were major complications. The annual remission rate for each year of treatment was 16% [CI 10-27%], which was higher in adults than non-adults (19% vs. 14%). However, it should be noted that this is not a true linear correlation, but a positive relationship can be suggested between time and remission rate. Meta-regression revealed that smoking had a significant lowering effect on remission rate.
CONCLUSIONS
Long-term ATD treatment is effective and safe, especially in adults, indicating that it should be considered as an alternative treatment for Graves' disease.
Topics: Antithyroid Agents; Drug Administration Schedule; Graves Disease; Humans; Methimazole; Propylthiouracil; Remission Induction; Time Factors; Treatment Outcome
PubMed: 28699478
DOI: 10.1089/thy.2016.0652 -
International Journal of Paediatric... Mar 2022PROP test (6-n-propylthiouracil) for the identification of genetic sensitivity to caries in young individuals has emerged as a useful tool for caries risk assessment. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
PROP test (6-n-propylthiouracil) for the identification of genetic sensitivity to caries in young individuals has emerged as a useful tool for caries risk assessment.
AIM
To systematically appraise available evidence on the association between genetic taste sensitivity, as detected by (PROP), and caries.
DESIGN
Seven databases, as of March 2020, were searched. Search terms included 'caries', 'taste predisposition', 'PROP'. Risk of bias assessment was performed using ROBINS-I tool, and the quality of evidence was assessed with GRADE. Random-effects meta-analyses were conducted to synthesize data, and pooled effects were estimated through standardized mean differences (SMDs) and associated confidence Intervals (95% CIs).
RESULTS
Of 92 articles initially retrieved, 12 were eligible for inclusion. Seven contributed to the meta-analyses. All were cross-sectional studies, with moderate-to-serious risk of bias. The non-tasters of PROP exhibited a significantly higher value for the DMFT compared with tasters (SMD: 1.23; 95% CI: 0.90, 1.56; P < .001), whereas the association for the DMFS was SMD: 1.34; 95% CI: 0.66, 2.01; P < .001 (non-tasters versus super-tasters). The quality of evidence was very low overall.
CONCLUSIONS
Within the limitations of this study, non-tasters to PROP exhibited higher caries experience, with subsequent clinical implications for follow-up and management of the 'high-susceptibility' individuals.
Topics: Adolescent; Child; Dental Caries; Humans; Propylthiouracil; Taste
PubMed: 34080244
DOI: 10.1111/ipd.12845 -
International Forum of Allergy &... Oct 2023Olfactory dysfunction has been reported to be involved in Parkinson's disease (PD) pathogenesis. However, gustatory dysfunction in PD has not been evaluated as in-depth... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Olfactory dysfunction has been reported to be involved in Parkinson's disease (PD) pathogenesis. However, gustatory dysfunction in PD has not been evaluated as in-depth as olfactory dysfunction. We reviewed the previously published studies regarding gustatory function in PD patients and suggested the possibility that gustatory dysfunction may also be associated with PD.
METHODS
MEDLINE, Cochrane Library, Embase, and PubMed databases were searched for studies evaluating gustatory function in PD patients. We used the standardized mean difference and a 95% confidence interval (CI) as the effect analysis index regarding the taste strip test. The relative risk and 95% CI were used as the effect analysis index for the questionnaires and propylthiouracil (PTU)/phenylthiocarbamide (PTC) perception test. Statistical heterogeneity was assessed using forest plots, Cochran's Q, and the I statistic; heterogeneity was considered high when I was over 75%. Publication bias was assessed by funnel plots and the Egger bias test.
RESULTS
We identified 19 articles that reported the results of gustatory function tests in PD patients and healthy controls. Most of these studies used various gustatory tests, including taste strips, questionnaires, taste solutions, PTU/PTC perception tests, and electrogustometry, and reported significantly lower gustatory function in PD patients than in the controls. However, several articles reported contradictory results.
CONCLUSIONS
Based on these studies, gustatory dysfunction is closely related to PD. However, the number of studies and enrolled subjects was small, and a unified gustatory function test was lacking. Therefore, further studies with larger populations and normalized gustatory function tests are needed.
Topics: Humans; Parkinson Disease; Taste Disorders; Smell; Taste Perception; Phenylthiourea; Olfaction Disorders
PubMed: 36934313
DOI: 10.1002/alr.23158 -
Clinical Endocrinology Jun 2022The risk of congenital anomalies following in utero exposure to thionamide antithyroid drugs (ATDs) is unresolved. Observational studies are contradictory and existing... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The risk of congenital anomalies following in utero exposure to thionamide antithyroid drugs (ATDs) is unresolved. Observational studies are contradictory and existing meta-analyses predate and preclude more recent studies. We undertook an updated meta-analysis of congenital anomaly risk in women exposed to carbimazole or methimazole (CMZ/MMI), propylthiouracil (PTU), or untreated hyperthyroidism in pregnancy.
METHODS
We searched Medline, Embase, and the Cochrane database for articles published up till August 2021. We pooled separate crude and adjusted risk estimates using random effects models and subgroup analyses to address heterogeneity.
RESULTS
We identified 16 cohort studies comprising 5957, 15,785, and 15,666 exposures to CMZ/MMI, PTU, and untreated hyperthyroidism, respectively. Compared to nondisease controls, adjusted risk ratio (RR) and 95% confidence intervals (95% CIs) for congenital anomalies was increased for CMZ/MMI (RR, 1.28; 95% CI, 1.06-1.54) and PTU (RR, 1.16; 95% CI, 1.08-1.25). Crude risk for CMZ/MMI was increased relative to PTU (RR, 1.20; 95% CI, 1.01-1.43). Increased risk was also seen with exposure to both CMZ/MMI and PTU, that is, women who switched ATDs in pregnancy (RR, 1.51; 95% CI, 1.14-1.99). However, the timing of ATD switch was highly variable and included prepregnancy switches in some studies. The excess number of anomalies per 1000 live births was 17.2 for patients exposed to CMZ/MMI, 9.8, for PTU exposure, and 31.4 for exposure to both CMZ/MMI and PTU. Risk in the untreated group did not differ from control or ATD groups. The untreated group was however highly heterogeneous in terms of thyroid status. Subgroup analysis showed more positive associations in studies with >500 exposures and up to 1-year follow-up.
CONCLUSIONS
ATD therapy carries a small risk of congenital anomalies which is higher for CMZ/MMI than for PTU and does not appear to be reduced by switching ATDs in pregnancy. Due to key limitations in the available data, further studies will be required to clarify the risks associated with untreated hyperthyroidism and with switching ATDs in pregnancy.
Topics: Abnormalities, Drug-Induced; Antithyroid Agents; Carbimazole; Female; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil
PubMed: 34845757
DOI: 10.1111/cen.14646 -
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 -
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