methimazole and Diabetes-Mellitus--Type-1

Although type 1 diabetes mellitus is largely associated with autoimmune thyroid disease and this entity has been recently referred to as autoimmune polyglandular syndrome type 3 variant, the autoimmune polyglandular syndrome type 3 variant in patients with rheumatoid arthritis has not been reported so far. We herein describe the first case of rheumatoid arthritis that was associated with autoimmune polyglandular syndrome type 3 variant.. A 77-year-old woman with a 15-year history of rheumatoid arthritis (RA) and a 10-year history of type 2 diabetes mellitus (T2D) presented with polyarthralgia and hyperglycaemia. Methotrexate 16 mg/week had been started from the onset and was continued, and adalimumab 40 mg/day was started for RA. Insulin treatment was also started for the diabetes. Laboratory examinations revealed high levels of C-reactive protein (CRP), rheumatoid factor, anti-cyclic citrullinated peptide antibody, and matrix metalloprotease 3. She was admitted multiple times as the symptoms recurred after treatment. Subsequently, based on the clinical course and investigations, she was diagnosed with type 1 diabetes mellitus and Graves' disease occurring during the course of RA and T2D. Her clinical course improved after reinforcement of insulin therapy and the addition of thiamazole therapy.. In patients with rheumatoid arthritis, the autoimmune polyglandular syndrome type 3 variant should be considered as the cause of the deterioration.

Topics: Aged; Antirheumatic Agents; Antithyroid Agents; Arthritis, Rheumatoid; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Hypoglycemic Agents; Insulin; Methimazole; Polyendocrinopathies, Autoimmune

Anti-N-methyl-D-aspartic acid-receptor (NMDA-R) encephalitis is a novel disease discovered within the past 10 years. It is an autoimmune disease (AD) that has been associated with other ADs, such as Graves' disease. However, association with autoimmune polyglandular syndromes (APS) has not been previously described. A 58-year-old woman presented with altered mental status and an 8-month history of weight loss, apathy and somnolence. Laboratory evaluation confirmed Graves' disease with thyrotoxicosis and type 1 diabetes mellitus. Despite treatment, she continued to have a fluctuating mental status. Further diagnostic evaluation included an abdominal MRI that showed a cystic lobular left adnexal mass. Serum anti-NMDA-R antibodies were positive, raising concern for NMDA-R encephalitis. Bilateral salpingo-oophorectomy was performed, with pathology consistent with cystadenofibroma. She had a favourable recovery with marked clinical improvement. Anti-NMDA-R antibodies were negative 2 months following surgery. The concomitant occurrence of APS and anti-NMDA-R encephalitis suggests a shared mechanism of autoimmune pathophysiology.

Topics: Abdomen; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antibodies; Antithyroid Agents; Cystadenofibroma; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Magnetic Resonance Imaging; Methimazole; Middle Aged; Ovarian Neoplasms; Polyendocrinopathies, Autoimmune; Receptors, N-Methyl-D-Aspartate

Thiamazole might trigger the onset of type 1 diabetes.

Topics: Antithyroid Agents; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Methimazole; Middle Aged

Graves' disease is the most common reason of hyperthyroidism in children. Graves' disease with accompanying functioning nodules is defined as Marine-Lenhart syndrome. This syndrome has not been described in children before. Here, a 15-year-old girl with Graves' disease and a coexisting cold nodule is presented. A thyroid scan showed diffuse uptake of Tc-99m pertechnatate in both lobes and decreased uptake in accordance with the left lobe nodule. The nodule was histologically diagnosed as benign. The patient was diagnosed with type 1 diabetes mellitus and polyglandular autoimmune syndrome during clinical follow-up. The differential diagnoses of Graves' disease with coexisting nodules should include the Marine-Lenhart syndrome. Treatment options should be determined taking this rare condition into account.

Topics: Adolescent; Antithyroid Agents; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Iodine Radioisotopes; Methimazole; Polyendocrinopathies, Autoimmune; Syndrome

Accumulating evidence supports a role for viruses in the pathogenesis of type 1 diabetes mellitus (T1DM). Activation of dsRNA-sensing pathways by viral dsRNA induces the production of inflammatory cytokines and chemokines that trigger beta cell apoptosis, insulitis, and autoimmune-mediated beta cell destruction. This study was designed to evaluate and describe potential protective effects of phenylmethimazole (C10), a small molecule which blocks dsRNA-mediated signaling, on preventing dsRNA activation of beta cell apoptosis and the inflammatory pathways important in the pathogenesis of T1DM. We first investigated the biological effects of C10, on dsRNA-treated pancreatic beta cells in culture. Cell viability assays, quantitative real-time PCR, and ELISAs were utilized to evaluate the effects of C10 on dsRNA-induced beta cell cytotoxicity and cytokine/chemokine production in murine pancreatic beta cells in culture. We found that C10 significantly impairs dsRNA-induced beta cell cytotoxicity and up-regulation of cytokines and chemokines involved in the pathogenesis of T1DM, which prompted us to evaluate C10 effects on viral acceleration of T1DM in NOD mice. C10 significantly inhibited viral acceleration of T1DM in NOD mice. These findings demonstrate that C10 (1) possesses novel beta cell protective activity which may have potential clinical relevance in T1DM and (2) may be a useful tool in achieving a better understanding of the role that dsRNA-mediated responses play in the pathogenesis of T1DM.

Topics: Animals; Apoptosis; Cell Line; Cell Survival; Chemokine CXCL10; Cytokines; Diabetes Mellitus, Type 1; Enterovirus; Female; Inflammation; Insulin-Secreting Cells; Methimazole; Mice; Mice, Inbred NOD; Real-Time Polymerase Chain Reaction; RNA, Double-Stranded; Signal Transduction; Thiones; Toll-Like Receptor 3; Up-Regulation

We developed an ultrasensitive enzyme immunoassay (ICT-EIA) for insulin autoantibody (IAA) measurements to better understand the pathophysiology of diabetes.. We developed ICT-EIA for IAA and measured IAA in 24 patients with type 1 diabetes, 30 patients with type 2 diabetes, 30 patients with methimazole-treated Graves' disease, 20 patients with Hashimoto's disease, 9 patients with hyperinsulinemia, and 73 healthy control subjects.. The conventional ELISA identified 3 patients with type 1 diabetes and 2 patients with type 2 diabetes as IAA positive, whereas 15 patients with type 1 diabetes, 7 patients with type 2 diabetes, and 4 patients with methimazole-treated Graves' disease were identified as IAA positive using ICT-EIA.. The ICT-EIA is an ultrasensitive and specific assay for IAA, and its use may provide a better understanding of the role of IAA in diabetes onset and progression.

Topics: Autoantibodies; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; Graves Disease; Hashimoto Disease; Humans; Hyperinsulinism; Immunoenzyme Techniques; Insulin; Insulin Antibodies; Methimazole; Sensitivity and Specificity

To ascertain the prevalence of Graves' disease (GD) in 1,323 Caucasian children with type 1 diabetes mellitus (T1DM), and to compare the course of GD in T1DM patients with the one observed in 109 Caucasian peer patients with GD but without T1DM (group B).. Only 7 patients (0.53%) of the T1DM series also presented with GD (group A)which was diagnosed many years after diabetes presentation. At GD diagnosis, the prevalence of preclinical hyperthyroidism was higher in group A (p = 0.0001), whereas serum TSH receptor antibodies (TRABs) were higher in group B (p = 0.04). The subsequent course with methimazole therapy and after its withdrawal was very similar in both groups.. GD prevalence in T1DM patients was 0.53%, i.e. almost identical to the one reported in the general population. GD was diagnosed many years after T1DM presentation. At GD diagnosis, the clinical picture was milder and TRAB serum levels were lower in diabetic patients. Preclinical diagnosis and early treatment of GD were not associated with better responsiveness to therapy. Screening programs based on periodical TRAB assessments are not useful in T1DM.

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Disease Progression; Female; Graves Disease; Humans; Hyperthyroidism; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Prevalence; Prognosis; Receptors, Thyrotropin; Retrospective Studies; Thyroiditis, Autoimmune

The prevalence and titer of glutamic acid decarboxylase antibody (GADAb) in type 1 diabetes mellitus (T1DM) has been reported to be higher in patients with autoimmune thyroid diseases (AITD) than those without them. However, we have no data about the influence of GADAb on AITD. We therefore studied the clinical characteristics of Graves' disease (GD) with GADAb in order to clarify the influence of GADAb on GD. Twelve GD patients with GADAb were enrolled and were compared to 40 GD patients without DM. The male to female ratio and age of onset of GD showed no statistical difference. The titer of TSH receptor antibody (TRAb) at the onset of GD was similar in both groups. Initial treatment with methimazole (MMI) was started in all patients with GADAb but radioactive iodine (RI) therapy was carried out in five patients because of adverse effects of MMI or poor control of hyperthyroidism. The initial titer of TRAb was significantly lower in patients treated with MMI alone compared to that in RI treated patients but none of the patients treated with MMI alone went into remission after more than 3-years of follow up. We also compared these GADAb-positive patients with 14 patients with diabetes mellitus who had matched clinical features. The number of diabetic patients who remained in possible remission was significantly higher than that of GADAb-positive patients (5 in 14 vs 0 in 12). Moreover, the rate of remission in the diabetic patients was no different from that of 21 control patients without diabetes followed for more than 7 years (5 in 14 vs 7 in 21). These data suggested that GADAb-positive patients are unlikely to go into remission with antithyroid agents. Therefore, definitive therapies might be preferable for the initial treatment of GADAb-positive patients.

Topics: Adult; Aged; Antithyroid Agents; Diabetes Mellitus, Type 1; Female; Glutamate Decarboxylase; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Iodine Radioisotopes; Male; Methimazole; Middle Aged

Topics: Antithyroid Agents; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Graves Disease; Humans; Male; Methimazole; Middle Aged

There is an increasing evidence that CD3+ cells, bearing gammadelta T cell receptors representing a minor subpopulation of T cells in the peripheral blood of humans are involved in the development of autoimmunity. The aim of the present study was determination of the gammadelta T cell subpopulation levels in the peripheral blood of subjects with Graves' disease and newly diagnosed type 1 diabetes in comparison to age-matched healthy controls. The percentages of CD3+, CD8+, gammadelta TCR+CD8+, gammadelta TCR+CD8- lymphocyte subsets were measured by flow cytometry. In the peripheral blood of newly diagnosed Graves' disease patients we showed a significant decrease of gammadelta TCR+ cells and gammadelta TCR+CD8- subset content in comparison to the percentages observed in subjects after methimazole treatment and in healthy controls. We also found a significant increase of gammadelta TCR+CD8+ cells in the peripheral blood of subjects with insulin-dependent diabetes, treated with insulin for 3-6 months. The present findings confirm our previous hypothesis that gammadelta TCR+CD8+ lymphocyte subset could play a role in the pathogenesis of diabetes type 1, probably as regulatory T cells and could be induced by delivery of exogenous insulin. Our results suggest that gammadelta T cells (gammadelta TCR+CD8- subset) could also play an important role in the development of Graves' disease and that their levels are modulated by thyreostatic treatment.

Topics: Adolescent; Adult; Antithyroid Agents; Case-Control Studies; CD3 Complex; CD8-Positive T-Lymphocytes; Diabetes Mellitus, Type 1; Female; Graves Disease; Humans; Male; Methimazole; Receptors, Antigen, T-Cell, gamma-delta; T-Lymphocyte Subsets

In a patient with hyperthyroidism and newly diagnosed insulin-dependent diabetes mellitus (IDDM), insulin action and clearance were studied before the initiation of antithyroid treatment and at 3-mo intervals for 1 yr thereafter. The sequential euglycemic clamp technique (5 mM) was used with insulin infusion rates of 0.5, 1.0, 2.0, and 5.0 mU.kg-1.min-1 in four steps of 2 h. The data were compared with nine control subjects and nine newly diagnosed euthyroid IDDM patients treated with insulin for 0.5 mo. Insulin sensitivity was increased in the patients (ED50 40 vs. 52 mU/L, range 43-70, in controls and 70 mU/L, range 59-120, in IDDM subjects). Insulin responsiveness was markedly elevated; the steady-state glucose infusion rate (SSGIR) of step 4 was 104 vs. 64 mumol.kg-1.min-1 (range 50-79) in controls and 61 mumol.kg-1.min-1 (range 47-69) in IDDM subjects. Insulin clearance was elevated in all steps (1-3, 20-23 vs. 9-15 ml.kg-1.min-1; 4, 18 vs. 6-12 ml.kg-1.min-1 in control and IDDM subjects). Parallel to the normalization of thyroid metabolism, insulin action (ED50 60 mU/L, SSGIR in step 4, 51 mumol.kg-1.min-1) and insulin clearance (steps 1-3, 11-14 ml.kg-1.min-1; step 4, 7 ml.kg-1.min-1) returned to the normal range in 6 mo. Both remained within the normal range until 12 mo. In the patient with newly diagnosed IDDM, the initial marked increases of insulin action and clearance were due to coexistent hyperthyroidism. With the amelioration of the hyperthyroid state, both processes became normal. The parallelism between insulin action and clearance suggests a functional relationship.

Topics: Adult; Diabetes Mellitus, Type 1; Follow-Up Studies; Glucose Clamp Technique; Humans; Hyperthyroidism; Insulin; Insulin, Regular, Pork; Male; Methimazole; Reference Values

Methimazole (MMI) administration decreases the incidence and intensity of experimentally induced lymphocytic thyroiditis (LT) in the female August rat and male A/J mouse. Spontaneous LT frequently occurs in the insulin-dependent type-I diabetic (DM) BB/W rat. Experiments were carried out to determine whether MMI administration to BB/W rats from 30 to 120 days of age would affect the incidence and intensity of spontaneous LT and the incidence of spontaneous DM. A total of 870 ng MMI/gm BW or saline (C) were administered ip daily to 77 BB/W rats beginning at age 30 days. Rats were killed at 120 days, blood obtained for measurement of serum T4, TSH, and anti-Tg Ab (ELISA), and thyroids removed for histology. MMI administration was associated with a decrease in the incidence of LT (31% vs. 55%; p less than 0.05) but no difference in the severity of the LT. Serum T4 was similar in the MMI and C groups, but serum TSH was slightly but significantly higher in MMI treated rats [43 +/- 6 (mean +/- SE) microU/ml vs. 30 +/- 2.5; p less than 0.05]. Serum anti-Tg Ab levels increased with age but MMI administration did not affect this rise. There was no significant difference in the incidence of insulin-dependent DM between the MMI and C rats (MMI, 56%; C, 74%).. MMI administration to the genetically predisposed insulin-dependent diabetes and LT prone BB/W rat during the age when LT spontaneously occurs reduced the incidence of LT.

Topics: Animals; Antibodies; Diabetes Mellitus, Type 1; Immunosuppression Therapy; Methimazole; Rats; Rats, Inbred Strains; Thyroglobulin; Thyroiditis, Autoimmune; Thyrotropin; Thyroxine

Topics: Child; Diabetes Mellitus, Type 1; Female; Humans; Hyperthyroidism; Methimazole; Thyroiditis, Autoimmune