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Frontiers in Immunology 2022The -glycome of immunoglobulin G (IgG), the most abundant glycoprotein in human blood serum, reflects pathological conditions of autoimmunity and is sensitive to...
Changes of IgG -Glycosylation in Thyroid Autoimmunity: The Modulatory Effect of Methimazole in Graves' Disease and the Association With the Severity of Inflammation in Hashimoto's Thyroiditis.
The -glycome of immunoglobulin G (IgG), the most abundant glycoprotein in human blood serum, reflects pathological conditions of autoimmunity and is sensitive to medicines applied in disease therapy. Due to the high sensitivity of -glycosylation, the IgG -glycan profile may serve as an indicator of an ongoing inflammatory process. The IgG structure and its effector functions are strongly dependent on the composition of -glycans attached to the Fc fragment, and the binding of antigens is regulated by Fab sugar moieties. Because of the crucial role of -glycans in IgG function, remodeling of its -oligosaccharides can induce pathological changes that ultimately contribute to the development of autoimmunity; restoration of their physiological structure is critical to the reduction of disease symptoms. Our recently published data have shown that the pathology of autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), is accompanied by alterations of the composition of IgG -glycans. The present study is a more in-depth investigation of IgG glycosylation in both AITDs, designed to determine the relationship between the severity of thyroid inflammation and IgG -glycan structures in HT, and to assess the impact of immunosuppressive therapy on the -glycan profile in GD patients. The study material consisted of human serum samples collected from donors with elevated anti-thyroglobulin (Tg) and/or anti-thyroperoxidase (TPO) IgGs without symptoms of hypothyroidism (n=68), HT patients characterized by high autoantibody titers and advanced destruction of the thyroid gland (n=113), GD patients with up-regulated IgG against thyroid-stimulating hormone receptor (TSHR) before (n=62) and after (n=47) stabilization of TSH level as a result of methimazole therapy (study groups), and healthy donors (control group, n=90). IgG was isolated from blood serum using protein G affinity chromatography. -glycans were released from IgG by PNGase F digestion and analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) after 2-aminobenzamide (2-AB) labeling. UPLC-MS chromatograms were integrated into 25 peaks (GP) in the Waters UNIFI Scientific Information System, and -glycans were assigned based on the glucose unit values and mass-to-charge ratios (m/z) of the detected ions. The Kruskal-Wallis non-parametric test was used to determine the statistical significance of the results (p<0.05). The obtained results suggest that modifications of IgG sialylation, galactosylation and core-fucosylation are associated with the severity of HT symptoms. Methimazole therapy implemented in GD patients affected the IgG -glycan profile; as a result, the content of the sialylated and galactosylated oligosaccharides with core fucose differed after treatment. Our results suggest that -glycosylation of IgG undergoes dynamic changes during the intensification of thyroiditis in HT, and that in GD autoimmunity it is affected significantly by immunosuppressive therapy.
Topics: Autoimmunity; Chromatography, Liquid; Glycosylation; Graves Disease; Hashimoto Disease; Humans; Immunoglobulin G; Inflammation; Methimazole; Polysaccharides; Tandem Mass Spectrometry; Thyroiditis
PubMed: 35370997
DOI: 10.3389/fimmu.2022.841710 -
Frontiers in Endocrinology 2021Atrial fibrillation is exceedingly rare in children with structurally and functionally normal hearts. We present a novel case of a 15-year-old female with known... (Review)
Review
Atrial fibrillation is exceedingly rare in children with structurally and functionally normal hearts. We present a novel case of a 15-year-old female with known hyperthyroidism who subsequently developed atrial fibrillation. She had been suffering from fatigue, heat intolerance and myalgias for 6 months. Her initial TSH was 0.01mU/L, and free T4 was 75.4 pmol/L, with a free T3 of >30.8 pmol/L. An electrocardiogram showed atrial fibrillation with a ventricular rate of 141 beats per minute. An echocardiogram demonstrated an enlarged left atrium and ventricle, with mild mitral regurgitation. She was treated with methimazole and underwent synchronized cardioversion. She subsequently returned to a euthyroid state and remained in normal sinus rhythm. In this case, we discuss the physiologic and arrhythmogenic properties of thyroid hormone, with a summary of the existing literature on atrial fibrillation in hyperthyroidism in children. Current guidelines for treatment of atrial fibrillation are also outlined.
Topics: Adolescent; Antithyroid Agents; Atrial Fibrillation; Electrocardiography; Female; Humans; Hyperthyroidism; Methimazole; Thyroid Function Tests; Treatment Outcome
PubMed: 34616360
DOI: 10.3389/fendo.2021.689497 -
BMC Endocrine Disorders Oct 2023This study aimed to evaluate the association between the initial dose of MMI and the clinical course, as well as adverse effects on young people with GD.
OBJECTIVE
This study aimed to evaluate the association between the initial dose of MMI and the clinical course, as well as adverse effects on young people with GD.
METHODS
One hundred and sixty-one children and adolescents with newly diagnosed GD were enrolled for this study and categorized into four groups based on initial serum-free T3 and T4 levels and daily MMI doses: Group A (mild, 0.3-0.5 mg/kg/day, n = 78), Group B (moderate, 0.6-0.8 mg/kg/day, n = 37), Group C (severe, 0.6-0.8 mg/kg/day, n = 24), and Group D (severe, 0.8-1.0 mg/kg/day, n = 22). The thyroid function, blood cell analysis and liver function were examined before treatment and at 4, 8 and 12 weeks after treatment. Outcome of long-term follow-up were also observed.
RESULTS
After 12 weeks of treatment, 91.0% of the patients in group A and 90.9% of the patients in group D recovered to normalization of FT3, which was slightly higher than the other two groups; 70.8% of the patients in group C recovered to normalization of FT4, which was slightly lower than that in the other three groups. The incidence of minor adverse effects was 12.8% in group A, 13.5% in group B, 16.7% in group C and 40.9% in group D (P < 0.01). Remission was achieved in 38 patients (23.6%).
CONCLUSIONS
Lower doses of MMI (0.3-0.5 mg/kg/day) are suitable for mild GD, and higher doses of MMI (0.6-0.8 mg/kg/day) are advisable for moderate or severe GD. Much higher doses of MMI (0.8-1.0 mg/kg/day) are harmful for initial use in children and adolescents with GD patients.
Topics: Humans; Adolescent; Child; Methimazole; Antithyroid Agents; Outpatients; Thyroxine; Graves Disease
PubMed: 37872592
DOI: 10.1186/s12902-023-01484-2 -
Medicina (Kaunas, Lithuania) Sep 2021Here, we report a case of an increase in serum creatine kinase (CK) concentration in an 11-year-old girl being treated for Graves' disease with antithyroid drugs (ATDs)....
Here, we report a case of an increase in serum creatine kinase (CK) concentration in an 11-year-old girl being treated for Graves' disease with antithyroid drugs (ATDs). The patient complained of myalgia two weeks after methimazole treatment. Triiodothyronine (T3) and free thyroxine (FT4) levels were normal, but the serum CK level was significantly elevated. After switching to propylthiouracil, the serum CK level decreased to normal, and the myalgia was resolved. The development of myopathy during the treatment of hyperthyroidism may be considered as an adverse reaction of MMI. In this report, we present a rare pediatric case, along with a discussion on the possible causes of myopathy that occurred during the treatment of Graves' disease. A careful follow-up (serum CK levels and thyroid function) and treatment reassessment should always be considered after antithyroid treatment.
Topics: Antithyroid Agents; Child; Female; Graves Disease; Humans; Methimazole; Myalgia; Thyroxine; Triiodothyronine
PubMed: 34684053
DOI: 10.3390/medicina57101016 -
Medicine Sep 2020Hyperthyroidism is a condition in which the thyroid gland is overreactive and produces excess amounts of thyroid hormone. Tripterygium glycosides, traditional Chinese... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hyperthyroidism is a condition in which the thyroid gland is overreactive and produces excess amounts of thyroid hormone. Tripterygium glycosides, traditional Chinese medicine has been widely used in the treatment of rheumatoid arthritis, nephrotic syndrome, hyperthyroidism and other diseases due to its anti-inflammatory and immunosuppressive effects. Evidence-based research is becoming popular especially with the application of Chinese traditional medicine. This paper systematically reviews and evaluates existing clinical data on the efficacy and safety of Tripterygium glycosides in the treatment of hyperthyroidism.
MATERIALS AND METHODS
PubMed, Cochrane library and EMBase, Chinese biomedical literature database (CBM), Chinese journal full-text database (CNKI), Wan fang digital periodical full-text database and China Science and Technology Journal Database (VIP) were searched based on the defined inclusion and exclusion criteria. Data extraction, research quality assessment and meta-analysis were conducted with RevMan5.3 software. Trial sequential analysis (TSA) was used to evaluate information size and treatment benefits.
RESULTS
Seventeen randomized controlled clinical trials with 1536 participants were included in the systematic review. In the meta-analysis, there were two subgroups: Tripterygium glycosides combined with thiamazole and prednisone group; Tripterygium glycosides combined with thiamazole group. The study results revealed that the degree of exophthalmos, FT3, FT4, BGP, and AKP decreased while TSH, SOD, GSH-PX increased after the addition of Tripterygium glycosides. This study results suggested that Tripterygium glycosides combined with western medicine are an effective therapy for hyperthyroidism.
CONCLUSION
This study indicates that Tripterygium glycosides enhances the effect of thiamazole and prednisone in the treatment of hyperthyroidism and without increasing the risk of adverse events.
Topics: Anti-Inflammatory Agents; Drug Therapy, Combination; Drugs, Chinese Herbal; Glycosides; Humans; Hyperthyroidism; Methimazole; Prednisone; Tripterygium
PubMed: 32957384
DOI: 10.1097/MD.0000000000022282 -
Medicine Dec 2017Insulin autoimmune syndrome (IAS) is an uncommon disorder characterized by hyperinsulinemic hypoglycemia related to insulin-binding autoantibodies. To the best of our... (Review)
Review
RATIONALE
Insulin autoimmune syndrome (IAS) is an uncommon disorder characterized by hyperinsulinemic hypoglycemia related to insulin-binding autoantibodies. To the best of our knowledge, we report the first case of a pregnant female with IAS.
PATIENT CONCERNS
The 26-year-old patient with Graves disease and 10 weeks pregnant developed IAS after approximately 6 months treatment with methimazole. The patient exhibited recurrent spontaneous hypoglycemia.
DIAGNOSES
On evaluation, laboratory findings detected both high fasting insulin (>1000 mIU/L) and insulin autoantibodies. An oral glucose tolerance test showed elevated insulin concentrations with disproportionately elevated C-peptide levels. The imaging study showed nomasslesionsinthepancreas,and the patient was clinically diagnosed with IAS.
INTERVENTIONS
The patient had an abortion, discontinued methimazole and switched to oral prednisone (30 mg once daily) and propylth- iouracil (100 mg 3 times daily) for 3 months.
OUTCOMES
At the 3-month follow-up visit, hypoglycemic episodes had disappeared and insulin antibody levels were no longer detectable.
LESSONS
We have described this case and reviewed the relevant literature concerning diagnosis and treatment of IAS. Importantly, this case indicates that clinicians should view pregnancy as another factor of hypoglycemia in IAS.
Topics: Abortion, Spontaneous; Adult; Autoimmune Diseases; Female; Follow-Up Studies; Gestational Age; Graves Disease; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Methimazole; Prednisone; Pregnancy; Pregnancy Complications; Rare Diseases; Risk Assessment; Syndrome
PubMed: 29390469
DOI: 10.1097/MD.0000000000009213 -
The Journal of Clinical Endocrinology... Jul 2010
Topics: Antithyroid Agents; Chemical and Drug Induced Liver Injury; Child; Humans; Methimazole; Propylthiouracil
PubMed: 20610609
DOI: 10.1210/jc.2010-1141 -
The Journal of Clinical Endocrinology... Jan 2024In 2005, a nationwide program of iodine prophylaxis on a voluntary basis was implemented in Italy by law. However, recent data on iodine status are lacking.
CONTEXT
In 2005, a nationwide program of iodine prophylaxis on a voluntary basis was implemented in Italy by law. However, recent data on iodine status are lacking.
OBJECTIVE
The aim of this study was to evaluate efficiency, effectiveness, and possible adverse effects (increased occurrence of thyroid autoimmunity and hyperthyroidism) of the Italian iodine prophylaxis program.
METHODS
From 2015 to 2019, a nationwide survey was performed. The use of iodized salt was evaluated in a sample of 164 593 adults and in 998 school canteens. A sample of 4233 schoolchildren (aged 11-13 years) was recruited to assess urinary iodine concentration, prevalence of goiter, and thyroid hypoechogenicity on ultrasound, with the latter being an indirect indicator of thyroid autoimmunity. Neonatal TSH values of 197 677 infants screened in regions representative of Northern, Central, and Southern Italy were analyzed to investigate the percentage of TSH values >5.0 mIU/L. Data on methimazole prescriptions were analyzed as indirect indicators of new cases of hyperthyroidism.
RESULTS
The prevalence of the use of iodized salt was 71.5% in adult population and 78% in school canteens. A median urinary iodine concentration of 124 μg/L, a prevalence of goiter of 2.2%, and a prevalence of thyroid hypoechogenicity of 5.7% were observed in schoolchildren. The percentage of neonatal TSH values >5.0 mIU/L resulted still higher (5.1%) than the World Health Organization threshold of 3.0%, whereas the prescriptions of methimazole showed a reduction of 13.5%.
CONCLUSION
Fifteen years of iodine prophylaxis have led to iodine sufficiency in Italy, although there still is concern about iodine nutritional status during pregnancy.
Topics: Adult; Female; Infant; Pregnancy; Infant, Newborn; Humans; Child; Methimazole; Goiter; Sodium Chloride, Dietary; Iodine; Hyperthyroidism; Italy; Prevalence; Thyrotropin
PubMed: 37820735
DOI: 10.1210/clinem/dgad593 -
Acta Oto-laryngologica Nov 2010It is suggested that TRPV1, 2, 3, and 4, TRPM5 and 8, and TRPA1 may play several roles in the olfactory epithelium (OE), contributing to olfactory chemosensation,...
Expression of transient receptor potential channel vanilloid (TRPV) 1–4, melastin (TRPM) 5 and 8, and ankyrin (TRPA1) in the normal and methimazole-treated mouse olfactory epithelium.
CONCLUSION
It is suggested that TRPV1, 2, 3, and 4, TRPM5 and 8, and TRPA1 may play several roles in the olfactory epithelium (OE), contributing to olfactory chemosensation, olfactory adaptation, olfactory–trigeminal interaction, and OE fluid homeostasis. In patients with olfactory disturbance, TRPV1 and TRPM8 may be closely related to a high rate of recognition of curry and menthol odors, while TRPV2 may also play a crucial role in the regeneration of olfactory receptor neurons.
OBJECTIVE
Expression of TRPV1–4, TRPM5 and 8, and TRPA1 in the normal and methimazole-treated mouse OE was analyzed.
METHODS
The localization of TRPV1–4, TRPM5 and 8, and TRPA1 in the OE of normal and methimazole-treated CBA/J mice was investigated by immunohistochemistry.
RESULTS
Normal OE showed a positive immunofluorescent reaction to TRPV1–4, TRPM5 and 8, and TRPA1. In lamina propria, the nerve fibers displayed TRPV 1, 2, and 3, TRPM8 and TRPA1. In the pathological condition, the expression of TRPV3, TRPV4, TRPM5, and TRPA1 was markedly reduced and took a long time to recover. In contrast, expression of TRPM8 was scarcely affected, even in the pathological condition, while TRPV1 and TRPV2 showed early recovery following methimazole treatment.
Topics: Animals; Calcium Channels; Fluorescent Antibody Technique; Immunohistochemistry; Injections, Intraperitoneal; Methimazole; Mice; Mice, Inbred CBA; Olfactory Mucosa; Reference Values; TRPA1 Cation Channel; TRPM Cation Channels; TRPV Cation Channels; Tissue Distribution; Transient Receptor Potential Channels
PubMed: 20586674
DOI: 10.3109/00016489.2010.489573 -
The Western Journal of Medicine May 1977Propylthiouracil and methimazole are used widely in the treatment of hyperthyroid disorders. The most important complication of the use of these drugs is depression of...
Propylthiouracil and methimazole are used widely in the treatment of hyperthyroid disorders. The most important complication of the use of these drugs is depression of the neutrophilic granulocyte count. Granulocytopenia occurs in about 4 percent and agranulocytosis occurs in about 0.3 percent of treated patients. Although this depression of the granulocyte count is reversible after the drug is discontinued, serious infection frequently accompanies agranulocytosis and accounts for almost all deaths related to the drugs. It is important to be aware of the clinical features of granulocytopenic reactions due to antithyroid drugs.
Topics: Agranulocytosis; Humans; Hypothyroidism; Methimazole; Propylthiouracil
PubMed: 867981
DOI: No ID Found