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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 -
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 -
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 -
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 -
Journal of Pediatric Endocrinology &... Mar 2023Thyroid storm (TS) is an uncommon but severe manifestation of hyperthyroidism and an endocrine emergency, as it is fatal if it goes unrecognized. In pediatrics, the... (Review)
Review
OBJECTIVES
Thyroid storm (TS) is an uncommon but severe manifestation of hyperthyroidism and an endocrine emergency, as it is fatal if it goes unrecognized. In pediatrics, the current literature is limited to case reports and case series. Current knowledge is extrapolated from adult data. This systematic review aims to present the epidemiology, most common etiologies, clinical presentation, and most accepted standard of care of TS in children. We aim to raise awareness of hyperthyroidism in the pediatric community.
CONTENT
The databases used were PubMed, google scholar, and LILACS, with the search terms "thyroid storm" AND "pediatrics". Studies included case reports and case series in English and Spanish from patients between the ages of 0-21 years with clinical features consistent with a diagnosis of TS based on ATA 2016, with or without reported scale scores, published between 2000 and 2022. Variables such as ethnicity, etiology, possible triggers, clinical features, and management components were analyzed and presented.
SUMMARY
We analyzed data from 45 patients. Their mean age was 11.25 years. The majority of them were from Asia (26%). The most common clinical features were sinus tachycardia (86.7%) and fever (64%), followed by altered mental status (46%) and diarrhea (31%). Graves' disease was the most common underlying condition, and infection the most common precipitant. Thirty one percent of patients received treatment with four components; however morbidity and mortality were not clinically significant with those who did not. TS has a heterogeneous presentation with multisystemic involvement. The most common symptoms in this review were fever, tachycardia, diarrhea, and altered mental status.
OUTLOOK
Further studies may be needed to best standardize the diagnosis and management of TS in children. Qualitative studies are needed to best assess the delay in diagnosis of hyperthyroidism and how this may impact prognosis in case patients were to develop TS.
Topics: Adult; Humans; Child; Infant, Newborn; Infant; Child, Preschool; Adolescent; Young Adult; Thyroid Crisis; Graves Disease; Prognosis
PubMed: 36318760
DOI: 10.1515/jpem-2022-0309 -
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 -
Journal of Endocrinological... Jun 2022Following the conventional 12-18 month antithyroid drug (ATD) treatment in Graves' disease (GD), 50% of patients experience relapse of hyperthyroidism. (Review)
Review
BACKGROUND
Following the conventional 12-18 month antithyroid drug (ATD) treatment in Graves' disease (GD), 50% of patients experience relapse of hyperthyroidism.
OBJECTIVE
The aim of this systematic scoping review was critical appraisal of duration of ATD therapy in the last 80 years.
METHODS
Articles were identified through the search of PubMed from January 1, 1941 to April 30, 2021. All study types were included. Articles were eligible if they reported data on the length of ATD treatment, particularly thyroid hormones and TSH receptor antibodies (TRAb) concentrations and specifically those with data on the remission and/or relapse rates.
RESULTS
We described major progress regarding the duration of ATD therapy and related outcomes at every 20 years. Articles of 1941-1960 were mainly concerned with determination of favorable treatment, minimal effective dose, side effects and rate of remission after < 12-month ATD therapy. Studies with larger number of patients and longer follow-ups appeared in 1961-1980; higher remission rate after 18-24 months versus 6 months of ATD therapy was reported. Articles of 1981-2000 focused on identification of factors associated with high relapse rates after discontinuation of ATD. In 2001-2021, ATD became the first choice of treatment in many countries. However, 12-18 months of ATD therapy was arbitrarily chosen as the appropriate option. According to recent studies, persistent normalization of TRAb occurs after 5 years of methimazole therapy and ATD treatment of > 60 months could offer a 4-year remission rate of 85%.
CONCLUSION
Long-term ATD treatment for more than 60 months is safe and effective, has the highest remission rate and cures most patients with GD; hence, it should be considered as the most appropriate duration for ATD therapy in these patients.
Topics: Antithyroid Agents; Graves Disease; Humans; Methimazole; Recurrence; Thyroid Hormones
PubMed: 35088381
DOI: 10.1007/s40618-021-01730-1 -
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 Endocrinology Jul 2021Comparison of studies on remission rates in pediatric Graves' disease is complicated by lack of uniformity in treatment protocols, remission definition, and follow-up...
OBJECTIVE
Comparison of studies on remission rates in pediatric Graves' disease is complicated by lack of uniformity in treatment protocols, remission definition, and follow-up duration. We performed a systematic review on remission rates in pediatric Graves' disease and attempted to create uniformity by recalculating remission rates based on an intention-to-treat analysis.
METHODS
PubMed and Embase were searched in August 2020 for studies on patients with Graves' disease: (i) 2 to 18 years of age, (ii) initially treated with methimazole or carbimazole for at least 18 months, (iii) with a follow-up duration of at least 1 year after cessation of methimazole or carbimazole. All reported remission rates were recalculated using an intention-to-treat analysis.
RESULTS
Of 1890 articles, 29 articles consisting of 24 patient cohorts were included with a total of 3057 patients (82.6% female). Methimazole or carbimazole was initially prescribed in 2864 patients (93.7%). Recalculation based on intention-to-treat analysis resulted in an overall remission rate of 28.8% (829/2880). Pooled remission rates based on treatment duration were 23.7, 31.0, 43.7, and 75% respectively after 1.5-2.5 years, 2.5-5 years, 5-6 years (two studies), and 9 years (single study) treatment duration. The occurrence of adverse events was 419 in 2377 patients (17.6%), with major side effects in 25 patients (1.1%).
CONCLUSIONS
Using a standardized calculation, the overall remission rate in methimazole-treated pediatric GD is 28.8%. A few small studies indicate that longer treatment increases the remission rate. However, evidence is limited and further research is necessary to investigate the efficacy of longer treatment durations.
Topics: Adolescent; Antithyroid Agents; Child; Graves Disease; Humans; Methimazole; Remission Induction; Treatment Outcome
PubMed: 34061770
DOI: 10.1530/EJE-21-0077 -
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