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Iranian Journal of Pharmaceutical... 2019The thionamide drugs, carbimazole and its metabolite methimazole (MMI), and propylthiouracil (PTU) have extensively been used in the management of various forms of... (Review)
Review
The thionamide drugs, carbimazole and its metabolite methimazole (MMI), and propylthiouracil (PTU) have extensively been used in the management of various forms of hyperthyroidism over the past eight decades. This review aims to summarize different aspects of these outstanding medications. Thionamides have shown their own acceptable efficacy and even safety profiles in treatment of hyperthyroidism, especially GD in both children and adults and also during pregnancy and lactation. Of the antithyroid drugs (ATDs) available, MMI is the preferred choice in most situations taking into account its better efficacy and less adverse effects accompanied by once-daily dose prescription because of a long half-life and similar cost. Considering the more severe teratogenic effects of MMI, PTU would be the selected ATD for treatment of hyperthyroidism during pre-pregnancy months and the first 16 weeks of gestation. Recent studies have confirmed the efficacy and safety of long-term MMI therapy with low maintenance doses for GD and toxic multinodular goiter. Despite the long-term history of ATD use, there is still ongoing debate regarding their pharmacology and diverse mechanisms of action, viz. their immunomodulatory effects, and mechanisms and susceptibility factors to their adverse reactions.
PubMed: 32802086
DOI: 10.22037/ijpr.2020.112892.14005 -
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 -
Proceedings (Baylor University. Medical... 2023Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune condition characterized by necrotizing inflammation of small vessels throughout the...
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune condition characterized by necrotizing inflammation of small vessels throughout the body. Pharmaceutical agents have been noted as an emerging etiology. This case presents a 41-year-old woman with a longstanding history of Graves' disease who previously failed other interventions and was started on propylthiouracil (PTU) nearly 2 years prior to symptom onset. The patient presented with severely pruritic purpuric lesions on her lower extremities that transformed into large bullae and became extremely painful. A thorough workup revealed only slightly elevated perinuclear ANCA and a mild protein S deficiency. Tissue biopsy was consistent with thrombotic vasculitis. A presumptive clinical diagnosis of PTU-induced vasculitis was made. Because the condition is relatively uncommon, the best course of treatment has not clearly been defined. Though PTU was immediately discontinued, the patient also required corticosteroids and referral for tissue debridement. While some cases have had symptom resolution after cessation of PTU, this case adds to a growing body of evidence for the timely use of corticosteroids in controlling PTU-induced vasculitis.
PubMed: 37614859
DOI: 10.1080/08998280.2023.2230830 -
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 -
Endocrine Practice : Official Journal... Mar 2021Thionamides (methimazole and propylthiouracil) have been associated with common side effects, such as rash and pruritus, and rare but serious adverse effects, such as...
OBJECTIVE
Thionamides (methimazole and propylthiouracil) have been associated with common side effects, such as rash and pruritus, and rare but serious adverse effects, such as agranulocytosis and hepatotoxicity. Methimazole is usually the preferred thionamide for the treatment of hyperthyroidism if the patient is not planning to conceive or not in the first trimester of pregnancy, given the less frequent dosing and lower risk of hepatotoxicity. In patients who experience rash or itching when treated with methimazole, switching them to propylthiouracil is one treatment option. Here we report our experience regarding desensitization to methimazole to allow continued treatment with methimazole as an alternative management option.
METHODS
We conducted a retrospective chart review of patients at a single institution who had side effects to methimazole and who were desensitized to methimazole under the supervision of an allergist. A total of 7 patients were included who experienced side effects to methimazole that did not include agranulocytosis or hepatotoxicity.
RESULTS
All 7 patients were able to take methimazole for treatment of their hyperthyroidism, either for continued medical therapy or as a bridge to definitive therapy, with either surgery or radioactive iodine treatment.
CONCLUSION
Under the supervision of an allergist, desensitization to methimazole is an option for treating patients who experience side effects to methimazole (excluding agranulocytosis and hepatotoxicity).
Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Methimazole; Pregnancy; Propylthiouracil; Retrospective Studies; Thyroid Neoplasms
PubMed: 33779553
DOI: 10.1016/j.eprac.2020.10.019 -
Deutsche Medizinische Wochenschrift... Oct 2021The diagnosis of Graves' disease is mainly based on ultrasonography and laboratory diagnostics. This includes the determination of the TSH value and the peripheral... (Review)
Review
DIAGNOSIS
The diagnosis of Graves' disease is mainly based on ultrasonography and laboratory diagnostics. This includes the determination of the TSH value and the peripheral thyroid hormones. TSH receptor antibody (TRAb) measurement is highly sensitive and specific for the detection of Graves' disease (GD) and helps to distinguish from autoimmune thyroiditis (AIT). However, as recent studies show, some may AIT patients may also reveal TRAb.
THERAPY
Current guidelines recommend primarily the use of thiamazol/carbimazole in GD. Due to the comparatively higher hepatotoxicity, propylthiouracil is not recommended as first line therapy. In case of relapse during 12 up to 18 months of antithyroid drug therapy or after a frustrating attempt at cessation, definitive therapy should be considered. Alternatively, in accordance with the current recommendations of the European Thyroid Association, drug therapy may be continued for up to 12 months after initial diagnosis.
PREGNANCY
The treatment of active GD during pregnancy is problematic due to diaplacental crossing of peripheral thyroid hormones, TSH receptor stimulating antibodies and antithyroid drugs. According to current guidelines, PTU is recommended during the first 16 weeks of pregnancy, whereas for the 2nd and 3 rd trimester no special recommendations are given. After that, you can choose which antithyroid drug might be used. The aim of antithyroid drug therapy during pregnancy is to achieve a suppressed TSH value together with normal or slightly increased fT4 while using lowest effective dose of antithyroid drug.
IMMUNE CHECKPOINT INHIBITORS (ICI)
The most common endocrine side effect with this therapy is thyroid dysfunction. Hyperthyroidism; occur most frequently in combination therapy (CTLA-4 / anti-PD-1 therapy) ICI mainly causes destructive thyroiditis with lymphocytic infiltration; GD is absolutely rare in this context and only few cases are described.
Topics: Antithyroid Agents; COVID-19; Carbimazole; Causality; Diagnosis, Differential; Female; Graves Disease; Humans; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Hormones; Thyrotropin; Ultrasonography
PubMed: 34644794
DOI: 10.1055/a-1258-5429 -
Thyroid : Official Journal of the... Dec 2023When the antithyroid drugs were discovered in the early 1940s, they were immediately recognized as a revolutionary new treatment for hyperthyroidism. Although much has...
When the antithyroid drugs were discovered in the early 1940s, they were immediately recognized as a revolutionary new treatment for hyperthyroidism. Although much has been learned about their mechanism of action and clinical utility, they continue to be used today in much the same way as they have been since their introduction. In 1995, Dr. Clark Sawin gave an address on the history of antithyroid drug development at the 11th International Thyroid Congress in Toronto, Ontario, Canada. In his review, Dr. Sawin recounted the original observations by Drs. Julia and Cosmo Mackenzie and Curt Richter at the Johns Hopkins University School of Medicine, and how their work ultimately led to Dr. Edwin (Ted) B. Astwood's seminal 1943 report on the use of thiourea and thiouracil in the Journal of the American Medical Association. He also described the development of propylthiouracil and methimazole as less toxic alternatives. He concluded his remarks by noting the often-serendipitous pathway of drug development and the role of pharmaceutical companies in the process. Antithyroid drugs remain a cornerstone of thyroid therapeutics. It is informative to review the process by which they came into use, as this is a seminal part of the history of thyroid disease in the 20th century. This knowledge may also spark additional research leading to new pharmacotherapies for patients with hyperthyroidism.
Topics: Male; Humans; Antithyroid Agents; Graves Disease; Methimazole; Propylthiouracil; Hyperthyroidism; Ontario
PubMed: 37594736
DOI: 10.1089/thy.2022.0410