Hyperthyroid Graves Research Articles

Effect of antithyroid drugs on the occurrence of antibodies against type 2 deiodinase (DIO2), which are involved in hyperthyroid Graves’ disease influencing the therapeutic efficacy

Graves' disease is an organ-specific autoimmune disease with hyperthyroidism, diffuse goiter and autoantibodies against TSH receptor, thyroid peroxidase (TPO) and/or thyroglobulin (Tg). Graves' hyperthyroidism is characterized by T3 dominance due to the conversion of T4 into T3 through type 1 and 2 deiodinase enzymes (DIO1, DIO2). Methimazole (MMI) and propylthiouracil (PTU) therapies inhibit thyroid hormone synthesis blocking the activity of deiodinase and TPO enzymes. The study investigated the occurrence of autoantibodies against DIO2 peptides (cys- and hom-peptides) with the effect of antithyroid drugs on their frequencies in 78 patients with Graves' disease and 30 controls. In hyperthyroidism, the presence of DIO2 peptide antibodies was as follows: 20 and 11 cases out of 51 for cys- and hom-peptide antibodies, respectively, of whom 8 cases possessed antibodies against both peptides. Antithyroid drugs differently influenced their frequencies, which were greater in PTU than in MMI (3/6 vs 13/45 cases, P < 0.016 for cys- and 0/6 vs 2/45 cases for hom-peptide antibodies). Antibodies against both peptides demonstrated more reduced levels of anti-TPO (P < 0.003) and anti-Tg antibodies (P < 0.002) compared with those without peptide antibodies. PTU compared with MMI increased the levels of TSH receptor antibodies (32.5 UI/l vs 2.68IU/l, P < 0.009). MMI treatment led to more reduced FT3 levels and FT3/FT4 ratios in hyperthyroid Graves' ophthalmopathy (P < 0.028 for FT3, P < 0.007 for FT3/FT4 ratio). In conclusion, the presence of DIO2 peptide antibodies is connected to Graves' hyperthyroidism influencing the levels of antibodies against TPO, Tg and TSH receptor, as well as the therapeutic efficacy of antithyroid drugs.

Predictors of Initial and Sustained Remission in Patients Treated with Antithyroid Drugs for Graves' Hyperthyroidism: The RISG Study.

Purpose. To study predictors of attaining (part 1) and sustaining (part 2) remission in patients with Graves' hyperthyroidism (GH) treated with antithyroid drugs (ATD). Methods. In the prospective first part, the included patients were treated with ATD until a prespecified definition of remission (thyrotropin > 0.4 mU/L and TSH-receptor antibodies (TRAb) ≤ 1. 0 IU/L in a patient receiving a methimazole dose ≤ 5 mg/day, on two occasions two months apart) was met, or for 24 months. In the second part, patients attaining remission in part 1 were randomized to treatment or observation and followed until relapse or for 24 months. Results. 173 patients completed study 1 and 53% attained remission. TRAb and age were the only significant predictors of remission. Patients with baseline TRAb below vs above 10 IU/L attained remission in 63% compared to 39%, and 5 months priorly (p<0.001). In study 2, 96.4% of the patients randomized to treatment (n=33) sustained remission compared to 66% in the observation group (n=33). Treatment arm was the only significant parameter (p<0.001) of sustained remission. Conclusion. Baseline TRAb was prognostic for attaining remission in GH. Consecutive TRAb measurements during treatment were not worthwhile, but a single measurement after 6-8 months in patients with initial TRAb < 10 IU/L could substantially shorten the treatment period in a subgroup of patients. Only 3.6% of the patients in remission experienced relapse during follow-up when treated with a combination of fixed low dose methimazole and L-T4. ClinTrial.gov registration number is NCT00796913.

Predicting the Early Risk of Ophthalmopathy in Graves' Disease Patients Using TCR Repertoire

Background: Graves' ophthalmopathy (GO), the common extrathyroidal manifestation in Graves' hyperthyroidism (GH), often has an unsatisfactory therapeutic effect due to late diagnosis. Methods: Firstly, we proposed a novel score termed TCR Clonal expansion and chaos Score (TCS) to characterize VJ. TCS score equals to the ratio between clonal expansion of TCR V-J combination and chaos of peptide similarity. Then, we sequenced the RNA transcripts from the complementarity determining region 3 (CDR3) of TCR Vβ from 100 peripheral blood samples, including 43 and 57 stable GH. Random forest method was applied to select candidate features with the best performance to classify and GH. Lastly, this model was applied in an independent validation dataset consisting of 18 stable samples and 17 samples who progressed to in the follow up visit. Findings: The leave-one-out cross validation showed this model with a sensitivity of 87.88% and a specificity of 81.08% to differentiate from stable GH. And it achieved a sensitivity and specificity of 70.59% and 72.22% for prediction progression in GH. Specifically, 12 of the 17 patients who were as developed symptoms of eyelid swelling, chemosis or proptosis in a median of 6.5 months (4-9.75 months, IQR). In addition, GO-free survival analysis demonstrated that predicted GO patients (n = 17) were significant difference with predicted GH patients (n = 18) in progression (P = 0.015, log-rank test). Interpretation: Our finding provides a proof of concept for diagnosis and prognosis using TCR repertoire and may help develop novel prophylactic strategy for and other autoimmune diseases. Funding Statement: This work was supported by the National Key R&D Program of China (grant NO. 2018YFC1311500 (B.S.), 2017YFC0907500 (K.Y.) and 2018YFC0910400 (K.Y.)), National Science Foundation of China (NSFC) (grant NO. 81670725 (B.S.), 81500690 (Y.W.), 31671372 (K.Y.), 61702406 (X.Y.)), the Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University, China (grant NO. XJTU1AF-CRF-2017-001 (B.S.)), Natural Science Foundation of Shaanxi Province (2018JM70990 (Y.W.)), Key Research and Development Project of Shaanxi Province (grant NO. 2017ZDXM-SF-060 (B.S.)), the Fundamental Research Funds for the Central Universities (1191329875 (Y.W.)), China Postdoctoral Science Foundation (224646(Y.W.)). Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: This study was approved by the Ethic Committee of the First Affiliated Hospital of Xi’an Jiaotong University (KYLLSL-2015-004-01). Informed consent was sought from all patients before screening and study entry.

Is Sex A Predictor of Outcome of Antithyroid Therapy of Graves Hyperthyroidism?

Is Sex A Predictor of Outcome of Antithyroid Therapy of Graves Hyperthyroidism?

A look at Graves’ hyperthyroidism in pregnancy

Maternal, obstetrical, and neonatal complications are increased in women with poorly controlled thyroid disease during pregnancy. Establishing the correct diagnosis and effectively managing Graves’ hyperthyroidism (GH) remains challenging for physicians due to several reasons including, but not limited to changes in thyroid physiology during pregnancy, effect of pregnancy on laboratory testing, and teratogenicity associated with anti-thyroid drugs. This paper will review the diagnosis and management of GH in pregnancy and address: (I) preconception counseling; (II) alterations in thyroid physiology in pregnancy; (III) thyroid laboratory testing; (IV) etiologies of hyperthyroidism; (V) pregnancy-related complications; (VI) maternal management; (VII) neonatal management; (VIII) ATDs and the associated maternal and fetal complications; and (IX) post-partum management. Establishing the diagnosis of GH early, maintaining euthyroidism throughout the duration of pregnancy, and avoiding overtreatment of the fetus with antithyroid drugs (ATDs) is essential to reducing the risk of complications for the mother, fetus, and newborn. The successful care of these complex patients requires close collaboration between the endocrinologist, maternal-fetal-medicine specialist, obstetrician, neonatologist, and pediatric endocrinologist.

Which Factors Predict the Outcome of Ablative Radioactive Iodine Treatment of Hyperthyroid Graves' Disease?

Which Factors Predict the Outcome of Ablative Radioactive Iodine Treatment of Hyperthyroid Graves' Disease?

Antithyroid Drugs Inactivate TSH Binding to the TSH Receptor by their Reducing Action.

(1) ATDs was pre-incubated with hTSHR coated tube for 1- 4 h, washed free of ATDs, and then 125I-bTSH binding to hTSHR after 1 h incubation was examined. MMI (10-40 mM) decreased 125I-bTSH binding in a dose-dependent manner and binding decreased proportionally as preincubation time increased from 1 to 4 h. PTU (10mM) slightly decreased binding, When reducing agents were pre-incubated with hTSHR for 2 h, 125I-bTSH binding similarly decreased. (2) Porcine thyroid membrane was pre-incubated with both agents for 2 h. Then, the washed or unwashed membrane was incubated with 125I-bTSH for 1 h. 125I-bTSH binding in both methods decreased. (3) When the effect of ATDs or reducing agents on the biological activity of 125I-bTSH and thyroid stimulating antibody (TSAb) was examined after gel-filtration of 125I-bTSH- and TSAb- treated with both reagents for 1 h, no inactivation was observed. (4) ATDs showed similar reducing action as reducing agents because iodine (I+) was reduced to I- by ATDs. ATDs inactivate the TSH-binding site of TSHR by reduction, although ATDs do not inactivate bTSH and TSAb activity. This suggests that TSAb would not stimulate the thyroid due to the inactivation of the TSHR when ATDs are administered to patients with Graves' disease.

Gut Microbiome in BALB/c and C57BL/6J Mice Undergoing Experimental Thyroid Autoimmunity Associate with Differences in Immunological Responses and Thyroid Function.

Experimental models of hyperthyroid Graves' disease (GD) and Graves' orbitopathy (GO) are efficiently developed by genetic immunisation by electroporation with human thyrotropin hormone receptor (hTSHR) A-subunit plasmid in female BALB/c (H-2d) mice. We investigated susceptibility in C57BL/6 J (H-2b) animals to allow studies on disease mechanisms in transgenic and immune response gene knock-out mice. Higher numbers of female C57BL/6 J were positive for pathogenic thyroid stimulating antibodies, but induced hyperthyroidism remained at a low frequency compared to BALB/c animals. Assessment of hTSHR specific T cells showed reduced proliferation in C57BL/6 J animals accompanied with anti-inflammatory IL-10, with less pro-inflammatory IFN-γ compared to BALB/c. Whilst the orbital tissue from immune BALB/c mice showed inflammation and adipogenesis, in contrast C57BL/6 J animals showed normal pathology. We characterised the gut microbiota using 16 S ribosomal RNA gene sequencing to explore its possible pathogenic role in the model. Despite being housed under identical conditions, we observed significantly different organisation of the microbiota (beta-diversity) in the two strains. Taxonomic differences were also noted, with C57BL/6 J showing an enrichment of Operational Taxonomic Units (OTUs) belonging to the Paludibacter and Allobaculum, followed by Limibacter, Anaerophaga and Ureaplasma genera. A higher number of genera significantly correlating with clinical features was observed in C57BL/6 J compared to BALB/c; for example, Limibacter OTUs correlated negatively with thyroid-stimulating antibodies in C57BL/6 J mice. Thus, our data suggest gut microbiota may play a pivotal immunomodulatory role that differentiates the thyroid function and orbital pathology outcome in these two inbred strains undergoing experimental GO.

Selenium in Graves Hyperthyroidism and Orbitopathy.

To review the in vitro and in vivo studies supporting a role of selenium for the treatment of mild Graves orbitopathy. Review of the current literature on the role of selenium in the management of Graves orbitopathy. Graves orbitopathy (GO) is a disfiguring and disabling disorder usually observed in patients with Graves hyperthyroidism, and more rarely in patients with hypothyroid autoimmune thyroiditis or in the absence of overt thyroid dysfunction. Noninvasive treatments include intravenous glucocorticoids and orbital radiotherapy and are generally offered to patients with moderately severe GO. In contrast, patients with mild GO are generally treated only with local measures. Thus, the benefits of intravenous glucocorticoids in mild GO are limited and do not justify the risks that the treatment carries. However, a medical treatment for mild GO is heavily wanted, as a relevant proportion of patients have a significant decrease in their quality of life, and GO can progress into more severe forms. Because of the role of oxidative stress in the pathogenesis of GO, an antioxidant approach has been proposed and the antioxidant agent selenium has been shown to be effective for GO. Studies have shown that a 6-month course of sodium selenite can improve the course of mild GO and prevent deterioration when compared with placebo.

Thyroid Stimulating Hormone Receptor Antibodies in Thyroid Eye Disease-Methodology and Clinical Applications.

Thyroid stimulating hormone receptor antibodies (TSHR-Ab) cause autoimmune hyperthyroidism and are prevalent in patients with related thyroid eye disease (TED). To provide a historical perspective on TSHR-Ab and to present evidence-based recommendations for clinical contemporary use. The authors review the recent literature pertaining to TSHR-Ab in patients with TED and describe the various immunoassays currently used for detecting TSHR-Ab and their clinical applications. We provide a historical summary and description of the various methods used to detect TSHR-Ab, foremost, the functional TSHR-Ab. Increasing experimental and clinical data demonstrate the clinical usefulness of cell-based bioassays for measurements of functional TSHR-Ab in the diagnosis and management of patients with autoimmune TED and in the characterization of patients with autoimmune-induced hyperthyroidism and hypothyroidism. Thyroid stimulating hormone receptor antibodies, especially the functional stimulating antibodies, are sensitive, specific, and reproducible biomarkers for patients with autoimmune TED and correlate well with clinical disease activity and clinical severity. Unlike competitive-binding assays, bioassays have the advantage of indicating not only the presence of antibodies but also their functional activity and potency. Measurement of TSHR-Ab (especially stimulating antibodies) is a clinically useful tool for the management of patients with TED.

A Validated Tool Can Predict Risk or Nonrisk of Graves’ Orbitopathy During Antithyroid Drug Treatment of Hyperthyroid Graves’ Disease

A Validated Tool Can Predict Risk or Nonrisk of Graves’ Orbitopathy During Antithyroid Drug Treatment of Hyperthyroid Graves’ Disease

Antithyroid drugs can be associated with increased frequency of antibodies against type 2 5'-deiodinase enzyme influencing their therapeutical effectiveness in hyperthyroid Graves' ophthalmopathy

Antithyroid drugs can be associated with increased frequency of antibodies against type 2 5'-deiodinase enzyme influencing their therapeutical effectiveness in hyperthyroid Graves' ophthalmopathy

Predictive score for the development or progression of Graves' orbitopathy in patients with newly diagnosed Graves' hyperthyroidism.

To construct a predictive score for the development or progression of Graves' orbitopathy (GO) in Graves' hyperthyroidism (GH). Prospective observational study in patients with newly diagnosed GH, treated with antithyroid drugs (ATD) for 18 months at ten participating centers from EUGOGO in 8 European countries. 348 patients were included with untreated GH but without obvious GO. Mixed effects logistic regression was used to determine the best predictors. A predictive score (called PREDIGO) was constructed. GO occurred in 15% (mild in 13% and moderate to severe in 2%), predominantly at 6-12 months after start of ATD. Independent baseline determinants for the development of GO were clinical activity score (assigned 5 points if score > 0), TSH-binding inhibitory immunoglobulins (2 points if TBII 2-10 U/L, 5 points if TBII > 10 U/L), duration of hyperthyroid symptoms (1 point if 1-4 months, 3 points if >4 months) and smoking (2 points if current smoker). Based on the odds ratio of each of these four determinants, a quantitative predictive score (called PREDIGO) was constructed ranging from 0 to 15 with higher scores denoting higher risk; positive and negative predictive values were 0.28 (95% CI 0.20-0.37) and 0.91 (95% CI 0.87-0.94) respectively. In patients without GO at diagnosis, 15% will develop GO (13% mild, 2% moderate to severe) during subsequent treatment with ATD for 18 months. A predictive score called PREDIGO composed of four baseline determinants was better in predicting those patients who will not develop obvious GO than who will.

Immunoglobulin E-Mediated Autoimmunity.

The study of autoimmunity mediated by immunoglobulin E (IgE) autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP), and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.

Functional diagnostics for thyrotropin hormone receptor autoantibodies: bioassays prevail over binding assays.

Autoantibodies to the thyrotropin hormone receptor (TSH-R) are directly responsible for the hyperthyroidism in Graves' disease and mediate orbital manifestations in Graves' orbitopathy (otherwise known as thyroid eye disease). These autoantibodies are heterogeneous in their function and collectively referred to as TRAbs. Measurement of TRAbs is clinically important for diagnosis of a variety of conditions and different commercial assays with high sensitivity and specificity are available for diagnostic purposes. This review provides overwhelming evidence that the TRAbs detected in binding assays by mainly the automated electrochemical luminescence immunoassays (ECLIA) do not distinguish TRAbs that stimulate the TSH-R (called TSIs or TSAbs) and TRAbs that just inhibit the binding of TSH without stimulating the TSH-R (called TBAbs). However, TSAbs and TBAbs have divergent pathogenic roles, and depending which fraction predominates cause different clinical symptoms and engender different therapeutic regimen. Therefore, diagnostic distinction of TSAbs and TBAbs is of paramount clinical importance. To date, only bioassays such as the Mc4 TSH-R bioassay (ThyretainTM, Quidel) and the Bridge assay (Immulite 2000, Siemens) can measure TSAbs, with only the former being able to distinguish between TSAbs and TBAbs. On this note, it is strongly recommended to only use the term TSI or TSAb when reporting the results of bioassays, whereas the results of automated TRAb binding assays should be reported as TRAbs (of undetermined functional significance). This review aims to present a technical and analytical account of leading commercial diagnostic methods of anti-TSH-R antibodies, a metaanalysis of their clinical performance and a perspective for the use of cell based TSH-R bioassays in the clinical diagnostics of Graves' disease.

Double-Blind, Placebo-Controlled, Randomized Trial of Selenium in Graves Hyperthyroidism

Supplemental selenium (Se) may affect the clinical course of Graves disease (GD). Evaluate efficacy of add-on Se on medical treatment in GD. Double-blind, placebo-controlled, randomized supplementation trial. Academic endocrine outpatient clinic. Seventy untreated hyperthyroid patients with GD. Additionally to methimazole (MMI), patients received for 24 weeks either sodium selenite 300 µg/d po or placebo. MMI was discontinued at 24 weeks in euthyroid patients. Response rate (week 24), recurrence rate (week 36), and safety. A response was registered in 25 of 31 patients (80%) and in 27 of 33 (82%) at week 24 [odds ratio (OR) 0.93; 95% confidence interval (CI), 0.26 to 3.25; P = 0.904] in the Se (+MMI) and placebo (+MMI) groups, respectively. During a 12-week follow-up, 11 of 23 (48%) and 12 of 27 (44%) relapsed (OR 1.13; 95% CI, 0.29 to 2.66; P = 0.81) in the Se and placebo groups, respectively. Serum concentrations of Se and selenoprotein P were unrelated to response or recurrence rates. At week 36, 12 of 29 (41%) and 15 of 33 (45%) were responders and still in remission in the Se and placebo groups, respectively (OR 0.85; 95% CI, 0.31 to 2.32; P = 0.80). Serum levels of free triiodothyronine/free tetraiodothyronine, thyroid-stimulating hormone receptor antibody, prevalence of moderate to severe Graves orbitopathy, thyroid volume, and MMI starting dose were significantly lower in responders than in nonresponders. A total of 56 and 63 adverse events occurred in the Se and placebo groups, respectively (P = 0.164), whereas only one drug-related side effect (2.9%) was noted in 35 patients on placebo + MMI. Supplemental Se did not affect response or recurrence rates in GD.

Iron metabolism in patients with Graves' hyperthyroidism.

Graves' hyperthyroidism (GH) interferes with iron metabolism and elevates ferritin. The precise mechanisms remain unclear. The influence of thyroid hormones on the synthesis/regulation of hepcidin, an important regulator of iron metabolism, remains uncharacterized. Prospective observational study. We included patients (n=31) with new-onset and untreated GH. Laboratory parameters indicative of iron metabolism (ferritin, transferrin, hepcidin), inflammatory markers/cytokines and smoking status were assessed at the diagnosis of GH (T0) and at euthyroidism (T1) in the same patients using multivariable analyses. Hepcidin was measured by mass spectrometry (hepcidinMS ) and ELISA (hepcidinEL ). The impact of T3 on hepatic hepcidin expression was studied in a cell culture model using HepG2 cells. Median ferritin levels were significantly lower and transferrin significantly higher at T1 than at T0. HepcidinMS levels were lower in males and females at T1 (statistically significant in males only). No statistically significant difference in hepcidinEL was detected between T0 and T1. Plasma levels of inflammatory markers (high-sensitive CRP, procalcitonin) and cytokines (interleukin 6, interleukin 1ß, tumour necrosis factor α) were not different between T0 and T1. Smokers tended to have lower fT3 and fT4 at T0 than nonsmoking GH patients. T3 significantly induced hepcidin mRNA expression in HepG2 cells. Iron metabolism in patients with GH undergoes dynamic changes in patients with GH that resemble an acute-phase reaction. Inflammatory parameters and cytokines were unaffected by thyroid status. Gender and smoking status had an impact on ferritin, hepcidin and thyroid hormones.

The effect of short-term treatment with lithium carbonate on the outcome of radioiodine therapy in patients with long-lasting Graves' hyperthyroidism.

The outcome of radioiodine therapy (RIT) in Graves' hyperthyroidism (GH) mainly depends on radioiodine (131I) uptake and the effective half-life of 131I in the gland. Studies have shown that lithium carbonate (LiCO3) enhances the 131I half-life and increases the applied thyroid radiation dose without affecting the thyroid 131I uptake. We investigated the effect of short-term treatment with LiCO3 on the outcome of RIT in patients with long-lasting GH, its influence on the thyroid hormones levels 7days after RIT, and possible side effects. Study prospectively included 30 patients treated with LiCO3 and 131I (RI-Li group) and 30 patients only with 131I (RI group). Treatment with LiCO3 (900mg/day) started 1day before RIT and continued 6days after. Anti-thyroid drugs withdrawal was 7days before RIT. Patients were followed up for 12months. We defined a success of RIT as euthyroidism or hypothyroidism, and a failure as persistent hyperthyroidism. In RI-Li group, a serum level of Li was 0.571 ± 0.156mmol/l before RIT. Serum levels of TT4 and FT4 increased while TSH decreased only in RI group 7days after RIT. No toxic effects were noticed during LiCO3 treatment. After 12months, a success of RIT was 73.3% in RI and 90.0% in RI-Li group (P < 0.01). Hypothyroidism was achieved faster in RI-Li (1st month) than in RI group (3rd month). Euthyroidism slowly decreased in RI-Li group, and not all patients became hypothyroid for 12months. In contrast, euthyroidism rapidly declined in RI group, and all cured patients became hypothyroid after 6months. The short-term treatment with LiCO3 as an adjunct to 131I improves efficacy of RIT in patients with long-lasting GH. A success of RIT achieves faster in lithium-treated than in RI group. Treatment with LiCO3 for 7days prevents transient worsening of hyperthyroidism after RIT. Short-term use of LiCO3 shows no toxic side effects.

Serum Immunogllobulin G Levels in Graves’ disease Patients at Various Stages of Antithyroid Therapy

Thirty six patients with Graves’ disease (GD), diagnosed on the basis of clinical examination and appropriate laboratory tests were classified into three groups (A-C): Group A: twelve newly diagnosed Graves’ disease patients; Group B: twelve hyperthyroid Graves’ disease patients on Antithyroid drug therapy and Group C: twelve Graves’ disease patients who had been rendered cuthyroid with Antithyroid drug (ATD) therapy, Serum lgG was determined by radial immunodiffusion method using commercially available kits (The Binding Site UK). The mean lgG in newly diagnosed patients with GD (Group A) was 18.78±1.81. It was 22.75 ± 1.89 in hyperthyroid GD patients on drug therapy (Group B), 14.3±0.8 in GD patients who were rendered euthyroid with drug therapy (Group C) and 11.85±0.72 in normal controls. The lgG level of group A patients were not significantly different from those of Group B. However, the levels of lgG and lgA were significantly low in group C Graves’ disease patients as compared to group A patients. A significant reduction in lgG LEVEL IN Graves’ disease patients who were rendered cuthyroid after Antithyroid drug therapy as compared to newly diagnosed Graves’ disease patients indicate the immunosuppressive effect of Antithyroid drug therapy.

Hyperthyroidism in Patients with Graves' Ophthalmopathy, and Thyroidal, Skeletal and Eye Muscle Specific Type 2 Deiodinase Enzyme Activities.

Graves' ophthalmopathy is characterized by hyperthyroidism, which is associated with higher serum T3 levels than T4 due to deiodinase enzymes.The effect of Graves' patient's sera (n=52) with elevated thyroid hormone and TSH receptor or thyroid peroxidase antibody (anti-TPO) levels was investigated on thyroidal, skeletal and eye muscle type 2 deiodinase enzyme (DII) activities. DII activities were measured with 125I-T4 substrate, while thyroid hormone and antibody levels with immunoassays.In Graves' ophthalmopathy, sera with elevated FT4 or FT3 levels reduced DII activites remarkably in all tissue fractions. Thyroidal DII activities were lower than those using eye muscle fraction (0.6±0.22 vs 1.14±0.43 pmol/mg/min, P<0.006). Effect of sera with increased FT3 levels demonstrated also reduced DII activities in patients with Graves' ophthalmopathy after methimazole therapy compared to those who had no ophthalmopathy (2.88±2 vs 20.42±11.82 pmol/mg/min, P<0.006 for thyroidal fraction, 4.07±2.72 vs 29.22±15.46 pmol/mg/min, P<0.004 for skeletal muscle, 5.3±3.47 vs 37.87±18.82 pmol/mg/min, P<0.003 for eye muscle). Hyperthyroid sera with TSH receptor antibodies resulted in increased DII activities, while sera with anti-TPO antibodies were connected to lower DII activities in Graves' ophthalmopathy.In summary, the actions of hyperthyroid sera derived from patients with Graves' disease were tested on tissue-specific DII activities. Elevated FT4 level-induced DII inactivation is present in Graves' ophthalmopathy, which seems to be also present at the beginning of methimazole therapy. Stimulating TSH receptor antibiodies increased DII activities via their nongenomic effects using sera of hyperthyroid Graves' ophthalmopathy, but anti-TPO antibodies could influence DII activities via altering FT4 levels.