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A Possible Role of Immunoglobulin E in Patients with Hyperthyroid Graves’ Disease

A Possible Role of Immunoglobulin E in Patients with Hyperthyroid Graves’ Disease. Presentation Outline. 1. Introduction 2. Graves’ Disease A. What is it? B. Predisposing factors Genetic factors Environmental and endogenous factors C. Epidemiology D. Clinical Manifestations E. Therapy

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A Possible Role of Immunoglobulin E in Patients with Hyperthyroid Graves’ Disease

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  1. A Possible Role of Immunoglobulin E in Patients with Hyperthyroid Graves’ Disease

  2. Presentation Outline • 1. Introduction • 2. Graves’ Disease • A. What is it? • B. Predisposing factors • Genetic factors • Environmental and endogenous factors • C. Epidemiology • D. Clinical Manifestations • E. Therapy • Antithyroid drugs • Radioactive iodine • Thyroidectomy

  3. 3. Immunoglobulin E • A. What is it? • 4. A Possible Role of Immunoglobulin E in Patients with Hyperthyroid Graves’ Disease • A. Introduction • B. Materials and Methods • C. Results • 5. Discussion and Conclusions

  4. What Is It? • Thyroid gland takes in iodine, iodinates thyroglobulin and stores it when thyroid hormones are not needed. • When thyroid hormones are needed, TSH from pituitary induces endocytosis and breakdown of T3 and T4. • In Graves’ disease, autoantibodies bind to the TSH receptor on thyroid cells and mimic the action of TSH which induces the continuous, chronic synthesis and release of thyroid hormones. • Graves’ opthalmopathy

  5. Predisposing Factors • Genetic Factors • No single gene is known to cause the disease or to be necessary for its development. • Environmental and Endogenous Factors • Sex- role of estrogen • Stress- job loss, divorce, bereavement • Smoking • Iodine deficiency • Aids and Multiple Sclerosis

  6. Epidemiology • 60-80% of patients with hyperthyroidism have graves’ disease. • Annual incidence in women over a 20 year period is 1 per 2000, with the highest risk of onset is between the ages of 40 and 60 years. • Graves’ disease is the most prevalent autoimmune disorder in the U.S. • 5 to 10 times more common in women than men and is unusual in children.

  7. Clinical Manifestations • Most common symptoms: • Nervousness, fatigue, a rapid heart beat or palpitations, heat intolerance and weight loss. • Goiter • Non-specific laboratory findings include high serum concentrations of bilirubin, aminotransferases, ferritin, and sex hormone-binding globulin. • Opthalmopathy

  8. Therapy • Antithyroid Drugs • Carbimazole, Methimazole and Propylthiouracil- inhibit the synthesis of thyroid hormone. • 30-40% of patients treated with antithyroid drugs remain euthyroid for 10 years. • If first treatment doesn’t work, there is little chance that second treatment will result in permanent remission.

  9. Radioactive Iodine • Recommended treatment for patients who are 50 years of age or older. • Main side effect is hypothyroidism. • Not recommended to be used in conjunction with antithyroid drugs. • Decreases effectiveness

  10. Subtotal Thyroidectomy • Preferred by some patients, especially those with a large goiter. • Should be treated with antithyroid drug until euthyroidism is achieved. • Most costly. • Hyperthyroidism is cured in 98% of patients.

  11. Immunoglobulin E • Immunoglobulins are the antigen binding molecules of B cells. • IgE is the immunoglobulin involved in allergic reactions. • IgE bound to mast cells trigger strong inflammatory reactions that are thought to help expel or destroy the parasites.

  12. A Possible Role of Immunoglobulin E in Patients with Hyperthyroid Graves’ Disease • Hyperthyroid graves’ disease is an autoimmune disorder characterized by presence of circulating TSH receptor antibody(TRAb) • Majority of activity of TRAb is in the IgG class but IgE may play a role. • Evidence- • IgE deposits in the thyroid and ocular muscles of patients. • Recurrence of graves’ disease can be induced by pollen allergy.

  13. To evaluate the potential relationship: • 1. Incidence of elevation of serum IgE among hyperthyroid graves’ disease, hashimotos thyroiditis, bronchial asthma, and pollen allergy were first studied. • 2. The past, present and family histories in patients with hyperthyroid graves’ disease in regard to pollen allergy and bronchial asthma was analyzed. • 3. The effects of antithyroid drugs on thyroid function and serum IgE levels were studied in hyperthyroid graves’ disease.

  14. Materials and Methods • 66 patients with hyperthyroid graves disease • 54 patients with hashimotos thyroiditis • 19 patients with bronchial asthma • 15 patients with pollen allergy

  15. Hyperthyroid patients treated with methimazole. Measured serum levels of TSH, T4 and TRAb. • Serum levels of IgE were measured every two months.

  16. Results • 1. Incidence and mean serum levels of elevated IgE in thyroid diseases, bronchial asthma, and pollen allergy.

  17. Patient Group (no.) Condition Incidence of IgE elevation (%) Serum IgE level (U/mL) Serum T4 (µg/dL) Serum TSH (mU/L) TRAb (%) 1 (66) Graves’ disease 85 (17 21.8 ± 5.8 <0.5 48.1 ± 20.2 19 with elevated IgE 29 602 (208 22.8 ± 6.3 <0.5 50.8 ± 20.6 47 without elevated IgE 71 38 (14 21.4 ± 5.6 <0.5 47.0 ± 20.2 2 (54) Hashimoto’s thyroiditis 36 (11 7.1 ± 2.3 20.1 ± 2.3 5.6 ± 11.9 6 with elevated IgE 11 244 (186 6.7 ± 2.3 20.9 ± 33.1 5.4 ± 6.4 48 without IgE elevation 89 28 (11 7.2 ± 2.3 20.0 ± 57.5 5.6 ± 12.5

  18. Table 1. Incidence of elevation of serum IgE level and mean value of serum IgE level in patients with hyperthyroid Graves’ disease, Hashimoto’s thyroiditis, bronchial asthma, and pollen allergy 3 (19) Bronchial asthma 295 (67 7.8 ± 0.8 2.4 ± 1.0 12 with elevated IgE 63 698 (257 7.8 ± 0.8 2.4 ± 1.0 7 without elevated IgE 37 67 (28 7.8 ± 0.7 2.6 ± 1.2 4 (15) Pollen allergy 105 (48 7.5 ± 0.7 2.1 ± 1.1 6 with elevated IgE 40 226 (172 7.6 ± 0.8 2.4 ± 1.5 9 without elevated IgE 60 64 (35 7.5 ± 0.6 1.9 ± 0.8 5 (41) Control subjects 34 (29 8.4 ± 1.5 2.7 ± 1.5 4.2 ± 2.7 1 with elevated IgE 2 340 7.6 1.0 40 without elevated IgE 98 32 (12 8.4 ± 1.5 2.7 ± 1.5 4.2 ± 2.7

  19. 2. Past, present, and/or family history in patients with IgE elevation in relation to bronchial asthma and pollen allergy.

  20. 3. Effect of methimazole treatment on serum levels of IgE and thyroid parameters.

  21. Discussion and Conclusions • The serum levels of IgE were elevated in 29% of patients with hyperthyroid graves’ disease. • It can be concluded that IgE elevation appears to be associated with autoimmune graves’ disease. • The relation with the most common allergic diseases, bronchial asthma and pollen allergy, which induce elevation of serum IgE also supported this conclusion. • A number of antibodies were present in patients with IgE elevation but not in patients without IgE elevation.

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