-
Frontiers in Endocrinology 2023The use of iodinated contrast media (ICM) can lead to thyrotoxicosis, especially in patients with risk factors, such as Graves' disease, multinodular goiter, older age,...
INTRODUCTION
The use of iodinated contrast media (ICM) can lead to thyrotoxicosis, especially in patients with risk factors, such as Graves' disease, multinodular goiter, older age, and iodine deficiency. Although hyperthyroidism may have clinically relevant effects, whether high-risk patients should receive prophylactic treatment before they are administered ICM is still debated.
AIM OF THE STUDY
We aimed to demonstrate the safety and efficacy of prophylactic treatment with sodium perchlorate and/or methimazole to prevent ICM-induced hyperthyroidism (ICMIH) in a population of high-risk cardiac patients. We ran a cost analysis to ascertain the most cost-effective prophylactic treatment protocol. We also aimed to identify possible risk factors for the onset of ICMIH.
MATERIALS AND METHODS
We performed a longitudinal retrospective study on 61 patients admitted to a tertiary-level cardiology unit for diagnostic and/or therapeutic ICM-procedures. We included patients with available records of thyroid function tests performed before and after ICM were administered, who were at high risk of developing ICMIH. Patients were given one of two different prophylactic treatments (methimazole alone or both methimazole and sodium perchlorate) or no prophylactic treatment. The difference between their thyroid function at the baseline and 11-30 days after the ICM-related procedure was considered the principal endpoint.
RESULTS
Twenty-three (38%) of the 61 patients were given a prophylactic treatment. Thyroid function deteriorated after the administration of ICM in 9/61 patients (15%). These cases were associated with higher plasma creatinine levels at admission, higher baseline TSH levels, lower baseline FT4 levels, and no use of prophylactic treatment. The type of prophylaxis provided did not influence any onset of ICMIH. A cost-benefit analysis showed that prophylactic treatment with methimazole alone was less costly per person than the combination protocol. On multivariate analysis, only the use of a prophylactic treatment was independently associated with a reduction in the risk of ICMIH. Patients not given any prophylactic treatment had a nearly five-fold higher relative risk of developing ICMIH.
CONCLUSION
Prophylactic treatment can prevent the onset of ICMIH in high-risk populations administered ICM. Prophylaxis is safe and effective in this setting, especially in cardiopathic patients. Prophylaxis with methimazole alone seems to be the most cost-effective option.
Topics: Humans; Contrast Media; Methimazole; Retrospective Studies; Hyperthyroidism; Graves Disease; Risk Factors
PubMed: 37255974
DOI: 10.3389/fendo.2023.1154251 -
CMAJ : Canadian Medical Association... Mar 2003Graves' disease is characterized by hyperthyroidism, diffuse goitre, ophthalmopathy and, rarely, dermopathy. Although diagnostic testing is straightforward once Graves'... (Review)
Review
Graves' disease is characterized by hyperthyroidism, diffuse goitre, ophthalmopathy and, rarely, dermopathy. Although diagnostic testing is straightforward once Graves' disease is suspected, physicians need to be aware of heterogeneous and even atypical presentations of the disease, particularly in elderly patients. Because morbidity may be associated with even subtle forms of hyperthyroidism, treatment promoting long-term euthyroidism is necessary. Although all of the available treatments are effective, compliance is best assured by a full discussion of the risks and benefits of each approach. This review focuses on issues of diagnosis and management that will allow the primary care physician to identify patients with Graves' disease and guide them to recovery.
Topics: Adult; Aged; Antithyroid Agents; Female; Graves Disease; Half-Life; Humans; Iodine Radioisotopes; Male; Methimazole; Thyroid Function Tests
PubMed: 12615754
DOI: No ID Found -
Clinics (Sao Paulo, Brazil) Jun 2015To evaluate the association of either propylthiouracil or methimazole treatment for hyperthyroidism during pregnancy with congenital malformations, relevant studies were... (Meta-Analysis)
Meta-Analysis Review
To evaluate the association of either propylthiouracil or methimazole treatment for hyperthyroidism during pregnancy with congenital malformations, relevant studies were identified by searching Medline, PubMed, the Cochrane Library and EMBASE. We intended to include randomized controlled trials, but no such trials were identified. Thus, we included cohort studies and case-control studies in this meta-analysis. A total of 7 studies were included in the meta-analyses. The results revealed an increased risk of birth defects among the group of pregnant women with hyperthyroidism treated with methimazole compared with the control group (odds ratio 1.76, 95% confidence interval 1.47-2.10) or the non-exposed group (odds ratio 1.71, 95% confidence interval 1.39-2.10). A maternal shift between methimazole and propylthiouracil was associated with an increased odds ratio of birth defects (odds ratio 1.88, 95% confidence interval 1.27-2.77). An equal risk of birth defects was observed between the group of pregnant women with hyperthyroidism treated with propylthiouracil and the non-exposed group (odds ratio 1.18, 95% confidence interval 0.97-1.42). There was only a slight trend towards an increased risk of congenital malformations in infants whose mothers were treated with propylthiouracil compared with in infants whose mothers were healthy controls (odds ratio 1.29, 95% confidence interval 1.07-1.55). The children of women receiving methimazole treatment showed an increased risk of adverse fetal outcomes relative to those of mothers receiving propylthiouracil treatment. We found that propylthiouracil was a safer choice for treating pregnant women with hyperthyroidism according to the risk of birth defects but that a shift between methimazole and propylthiouracil failed to provide protection against birth defects.
Topics: Abnormalities, Drug-Induced; Adult; Antithyroid Agents; Case-Control Studies; Cohort Studies; Confidence Intervals; Female; Humans; Hyperthyroidism; Infant, Newborn; Male; Methimazole; Odds Ratio; Pregnancy; Pregnancy Complications; Propylthiouracil; Risk
PubMed: 26106966
DOI: 10.6061/clinics/2015(06)12 -
Frontiers in Endocrinology 2023Methimazole (MMI) represents the conventional therapeutic agent for Graves' disease (GD) hyperthyroidism, but MMI efficacy is limited since it marginally affects the...
INTRODUCTION
Methimazole (MMI) represents the conventional therapeutic agent for Graves' disease (GD) hyperthyroidism, but MMI efficacy is limited since it marginally affects the underlying autoimmune process. In a previous study, we randomly assigned 42 newly diagnosed GD patients with insufficient vitamin D (VitD) and selenium (Se) levels to treatment with MMI alone (standard) or combined with selenomethionine and cholecalciferol (intervention) and observed a prompter resolution of hyperthyroidism in the intervention group.
METHODS
In the present study, we aimed to explore changes in peripheral T regulatory (Treg) and circulating natural killer (NK) cell frequency, circulating NK cell subset distribution and function, during treatment.
RESULTS
At baseline, circulating total CD3CD56NK cells and CD56 NK cells were significantly higher in GD patients than in healthy controls (HC) (15.7 ± 9.6% vs 9.9 ± 5.6%, p=0.001; 12.2 ± 10.3% vs 7.3 ± 4.1%, p=0.02, respectively); no differences emerged in Treg cell frequency. Frequencies of total NK cells and CD56 NK cells expressing the activation marker CD69 were significantly higher in GD patients than in HC, while total NK cells and CD56 NK cells expressing CD161 (inhibitory receptor) were significantly lower. When co-cultured with the K562 target cell, NK cells from GD patients had a significantly lower degranulation ability compared to HC (p<0.001). Following 6 months of treatment, NK cells decreased in both the intervention and MMI-alone groups, but significantly more in the intervention group (total NK: -10.3%, CI 95% -15.8; -4.8% vs -3.6%, CI 95% -9; 1.8%, p=0.09 and CD56 NK cells: -6.5%, CI 95% -10.1; -3 vs -0.9%, CI 95% -4.4; 2%, p=0.03). Compared to baseline, CD69 NK cells significantly decreased, while degranulation ability slightly improved, although no differences emerged between the two treatment groups. Compared to baseline, Treg cell frequency increased exclusively in the intervention group (+1.1%, CI 95% 0.4; 1.7%).
DISCUSSION
This pilot study suggested that VitD and Se supplementation, in GD patients receiving MMI treatment, modulates Treg and NK cell frequency, favoring a more pronounced reduction of NK cells and the increase of Treg cells, compared to MMI alone. Even if further studies are needed, it is possible to speculate that this immunomodulatory action might have facilitated the prompter and better control of hyperthyroidism in the supplemented group observed in the previous study.
Topics: Humans; Methimazole; Antithyroid Agents; Selenium; Vitamin D; Pilot Projects; Graves Disease; Hyperthyroidism; Vitamins; Dietary Supplements
PubMed: 37124743
DOI: 10.3389/fendo.2023.1145811 -
Endocrine Journal Apr 2019Methimazole (MMI) and propylthiouracil (PTU) are commonly used for the treatment of Graves' disease. They share similar inhibitory effects on thyroid hormone...
Methimazole (MMI) and propylthiouracil (PTU) are commonly used for the treatment of Graves' disease. They share similar inhibitory effects on thyroid hormone biosynthesis by interfering with thyroid peroxidase (TPO)-mediated oxidation and organification of iodine. However, their potential effects on other thyroid functional molecules have not been explored in depth. To identify novel effects of MMI and PTU, DNA microarray analysis, real-time PCR, Western blotting, immunofluorescence staining and confocal laser scanning microscopy were performed using FRTL-5 rat thyroid cells. DNA microarray analysis indicated that both MMI and PTU suppress iodotyrosine deiodinase 1 (Iyd, Dehal1) mRNA levels. Further studies revealed that Dehal1 mRNA levels was stimulated by TSH, insulin and serum, while it was suppressed by iodine and a follicular concentration of thyroglobulin. MMI and PTU significantly suppressed Dehal1 expression induced by TSH, insulin and serum. On the other hand, although MMI suppressed Dehal1 expression in the absence of TSH, PTU only weakly suppressed Dehal1 without TSH. These results suggest that PTU and MMI may use different mechanisms to regulate Dehal1 expression, and TSH may play essential and differential roles in mediating PTU and MMI signals in thyrocytes. The drugs also inhibited re-distribution of Dehal1 protein into newly formed lysosomes following thyroglobulin endocytosis. These findings imply complex and multifaceted regulation of Dehal1 in the thyroid and suggest that MMI and PTU modulate Dehal1 expression and distribution of the protein in thyrocytes to exert their effect.
Topics: Animals; Antithyroid Agents; Cell Line; Insulin; Iodide Peroxidase; Methimazole; Propylthiouracil; Rats; Thyroid Epithelial Cells; Thyrotropin
PubMed: 30814441
DOI: 10.1507/endocrj.EJ18-0380 -
Toxicology Letters Jan 2022Disruption of the thyroid hormone system during development can impair brain development and cause irreversible damage. Some thyroid hormone system disruptors act by...
Disruption of the thyroid hormone system during development can impair brain development and cause irreversible damage. Some thyroid hormone system disruptors act by inhibiting the thyroperoxidase (TPO) enzyme, which is key to thyroid hormone synthesis. For the potent TPO-inhibiting drug propylthiouracil (PTU) this has been shown to result in thyroid hormone system disruption and altered brain development in animal studies. However, an outstanding question is which chemicals beside PTU can cause similar effects on brain development and to what degree thyroid hormone insufficiency must be induced to be able to measure adverse effects in rats and their offspring. To start answering these questions, we performed a perinatal exposure study in pregnant rats with two TPO-inhibitors: the drug methimazole (MMI) and the triazole herbicide amitrole. The study involved maternal exposure from gestational day 7 through to postnatal day 22, to MMI (8 and 16 mg/kg body weight/day) or amitrole (25 and 50 mg/kg body weight/day). Both MMI and amitrole reduced serum T4 concentrations in a dose-dependent manner in dams and offspring, with a strong activation of the hypothalamic-pituitary-thyroid axis. This reduction in serum T4 led to decreased thyroid hormone-mediated gene expression in the offspring's brains and caused adverse effects on brain function, seen as hyperactivity and decreased habituation in preweaning pups. These dose-dependent effects induced by MMI and amitrole are largely the same as those observed with PTU. This demonstrates that potent TPO-inhibitors can induce effects on brain development in rats and that these effects are driven by T4 deficiency. This knowledge will aid the identification of TPO-inhibiting thyroid hormone system disruptors in a regulatory context and can serve as a starting point in search of more sensitive markers of developmental thyroid hormone system disruption.
Topics: Amitrole; Animals; Animals, Newborn; Antithyroid Agents; Disease Models, Animal; Enzyme Inhibitors; Female; Maternal Exposure; Methimazole; Motor Activity; Neurotoxicity Syndromes; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Signal Transduction; Thyroid Function Tests; Thyroid Gland
PubMed: 34757178
DOI: 10.1016/j.toxlet.2021.10.010 -
Journal of Cachexia, Sarcopenia and... Feb 2022Thyroid hormone excess induces protein energy wasting, which in turn promotes muscle weakness and bone loss in patients with Graves' disease. Although most studies have...
BACKGROUND
Thyroid hormone excess induces protein energy wasting, which in turn promotes muscle weakness and bone loss in patients with Graves' disease. Although most studies have confirmed a relationship between thyrotoxicosis and muscle dysfunction, few have measured changes in plasma metabolites and immune cells during the development and recovery from thyrotoxic myopathy. The aim of this study was to identify specific plasma metabolites and T-cell subsets that predict thyrotoxic myopathy recovery in patients with Graves' disease.
METHODS
One hundred patients (mean age, 40.0 ± 14.2 years; 67.0% female), with newly diagnosed or relapsed Graves' disease were enrolled at the start of methimazole treatment. Handgrip strength and Five Times Sit to Stand Test performance time were measured at Weeks 0, 12, and 24. In an additional 35 patients (mean age, 38.9 ± 13.5 years; 65.7% female), plasma metabolites and immunophenotypes of peripheral blood were evaluated at Weeks 0 and 12, and the results of a short physical performance battery assessment were recorded at the same time.
RESULTS
In both patient groups, methimazole-induced euthyroidism was associated with improved handgrip strength and lower limb muscle function at 12 weeks. Elevated plasma metabolites including acylcarnitines were restored to normal levels at Week 12 regardless of gender, body mass index, or age (P trend <0.01). Senescent CD8 CD28 CD57 T-cell levels in peripheral blood were positively correlated with acylcarnitine levels (P < 0.05) and decreased during thyrotoxicosis recovery (P < 0.05). High levels of senescent CD8 T cells at Week 0 were significantly associated with small increases in handgrip strength after 12 weeks of methimazole treatment (P < 0.05), but not statistically associated with Five Times Sit to Stand Test performance.
CONCLUSIONS
Restoring euthyroidism in Graves' disease patients was associated with improved skeletal muscle function and performance, while thyroid hormone-associated changes in plasma acylcarnitines levels correlated with muscle dysfunction recovery. T-cell senescence-related systemic inflammation correlated with plasma acylcarnitine levels and was also associated with small increases in handgrip strength.
Topics: Adult; CD8-Positive T-Lymphocytes; Female; Graves Disease; Hand Strength; Humans; Male; Methimazole; Middle Aged; Muscular Diseases
PubMed: 34970859
DOI: 10.1002/jcsm.12889 -
Frontiers in Cellular and Infection... 2022Immune dysfunction caused by environmental factors plays an important role in the development of Graves' disease (GD), and environmental factors are closely related to...
Immune dysfunction caused by environmental factors plays an important role in the development of Graves' disease (GD), and environmental factors are closely related to the intestinal flora. Our previous study showed significant changes in the intestinal flora in GD patients compared with healthy volunteers. This study analyzed the relationships between changes in the intestinal flora, thyroid function and relevant thyroid antibodies in GD patients before and after methimazole treatment. The subjects were divided into the UGD group (18 newly diagnosed GD patients), the TGD group (10 GD patients with normal or approximately normal thyroid function after methimazole treatment) and the NC group (11 healthy volunteers). Their fresh stool samples were sent for 16S rRNA gene amplification and Illumina platform sequencing. The correlations of the relative abundance of with the levels of TRAb, TgAb and TPOAb in the NC group and the UGD group were analyzed. A total of 1,562,445 high-quality sequences were obtained. In the UGD group, the abundances of and were higher than that in the NC group; abundance in the TGD group was higher than that in the NC group, while and abundances were lower than that in the NC group; and abundances in the UGD group were higher than that in the TGD group. The predominant abundance distribution of Bifidobacteriaceae in the UGD group at the family level was superior to that in the NC group. The abundance of was positively correlated with the levels of TRAb, TgAb, and TPOAb. The biological diversity of the intestinal flora was reduced in GD patients. After methimazole treatment, the composition of the intestinal flora was significantly altered. The change in abundance was positively correlated with TRAb, TgAb and TPOAb, suggesting that it might be related to the immune mechanism of GD. The results of this study may deepen our understanding of the pathogenesis of GD and provide a new idea for the treatment of GD.
Topics: Feces; Gastrointestinal Microbiome; Graves Disease; Humans; Methimazole; RNA, Ribosomal, 16S
PubMed: 35402292
DOI: 10.3389/fcimb.2022.794711 -
Endocrinology and Metabolism (Seoul,... Jun 2021Graves' disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through...
Graves' disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through inhibition of thyroid hormone synthesis or destruction of the thyroid gland. Recurrence after antithyroid drug (ATD) treatment is common. Recent studies have shown that the longer is the duration of use of ATD, the higher is the remission rate. Considering the relationship between clinical outcomes and iodine intake, recurrence of Graves' disease is more common in iodine-deficient areas than in iodine-sufficient areas. Iodine restriction in an iodine-excessive area does not improve the effectiveness of ATD or increase remission rates. Recently, Danish and Korean nationwide studies noted significantly higher prevalence of birth defects in newborns exposed to ATD during the first trimester compared to that of those who did not have such exposure. The prevalence of birth defects was lowest when propylthiouracil (PTU) was used and decreased by only 0.15% when methimazole was changed to PTU in the first trimester. Therefore, it is best not to use ATD in the first trimester or to change to PTU before pregnancy.
Topics: Antithyroid Agents; Female; Graves Disease; Humans; Infant, Newborn; Methimazole; Pregnancy; Propylthiouracil; Thyrotropin
PubMed: 34130446
DOI: 10.3803/EnM.2021.1070 -
Indian Journal of Pharmacology 2016Some cases of acute pancreatitis have been reported to be associated with use of methimazole. The aim of this study was to investigate the relationship between use of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Some cases of acute pancreatitis have been reported to be associated with use of methimazole. The aim of this study was to investigate the relationship between use of methimazole and risk of acute pancreatitis on the basis of a systematic analysis.
METHODS
This was a population-based case-control study analyzing the database of the Taiwan National Health Insurance Program. There were 5764 individuals aged 20-84 years with a first attack of acute pancreatitis from 1998 to 2011 as the cases and 23,056 randomly selected sex- and age-matched individuals without acute pancreatitis as the controls. Use of methimazole was categorized as "never use" and "ever use." We estimated the relative risk of acute pancreatitis associated with the use of methimazole by calculating the odds ratio (OR) with 95% confidence interval (CI) using a multivariable logistic regression model.
RESULTS
After adjustment for confounding factors, the OR of acute pancreatitis was 0.91 in individuals with ever use of methimazole, when compared with individuals with never use of methimazole (95% CI, 0.60-1.38). Unlike methimazole use, alcohol-related disease, biliary stone, cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, hepatitis B, hepatitis C, and hypertriglyceridemia were factors significantly associated with acute pancreatitis.
CONCLUSIONS
Our study does not detect a substantial association between the use of methimazole and risk of acute pancreatitis on the basis of systematic analysis. There appears to be a discrepancy between case reports and our systematic analysis about the association between the use of methimazole and risk of acute pancreatitis.
Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Methimazole; Middle Aged; Pancreatitis; Taiwan; Young Adult
PubMed: 27127323
DOI: 10.4103/0253-7613.178841