Autoimmune Mechanism and Recurrence Risk in Graves' Disease

*Vasudha Bakshi and Gollapalli Rajeev Kumar*

### **Abstract**

Graves' Disease (GD) is an autoimmune thyroid disorder where autoantibodies are produced against TSH (Thyroid Stimulating Hormone) receptor causing thyrotoxicosis. It is characterized by goiter, ophthalmopathy, and occasionally pretibial myxedema. The autoimmune mechanism causing disease is not well understood and it is complex. It involves multifactorial etiology involving environmental and genetic factors. Smoking and positive family history contributing to the development of GD. GD can be diagnosed based on the clinical manifestation and demonstrating low concentration of TSHs, high TRab (Thyroid Stimulating Hormone receptor autoantibodies), and high FT4 (Free thyroxine) concentration. Current treatment options aimed at stable restoration of euthyroidism by following different modalities of suppressing thyroid gland using antithyroid drugs, removing/ablating thyroid gland by surgery, and radioactive iodine treatment with iodine- 131.

**Keywords:** Graves' Disease, Thyroid Stimulating Hormone, Thyroid Stimulating Hormone receptor autoantibodies, Free thyroxine

#### **1. Introduction**

In this particular, Graves' Disease (GD) an autoimmune disorder, caused by excessive secretion of the glandular thyroid hormones by the thyroid follicles, which is related to the progressive hyperthyroidism condition. It is found to be the main cause of hyperthyroidism. The annual incidence has been reported of about 14–50 cases per 100,000 populations [1]. The disease may affect at any age and the incidence increases with age. The peak incidence of GD is between 30 and 50 years. It is generally accepted that younger patients have a severe immune system disorder where GD is predominantly found [1]. Few studies showed that younger patients are having poorer responses to ATD and poor prognosis with recurrent risk [2–4]. The lifetime risk of getting Graves' Disease is roughly 6 times higher in women than in men [1]. The exact mechanism of affecting the different gender is not known but believed to be associated with different sex hormones. Females are being affected more and the strongest risk factor contributed to the development of GD is estrogen. Estrogen influences B- cell functioning and regulates the immune system [5]. In GD patients, elevated estradiol relates to TRAb (TSH receptor antibody) positivity [6]. The risk of recurrence of GD after the withdrawal of the anti-thyroid drugs (ATG) is majorly seen in male GD patients [7, 8]. Large goiter with severe immune disorders and genetic aspects are associated with the development of GD in males. Genetic factors associated with GD are cytotoxic T-associated lymphocyte factor-4 (CTLA4) rs231779 and rs231775, especially Thyroglobulin (Tg) and TSHR

polymorphisms are linked with relapse in GD after the withdrawal of ATD. At four weeks following the completion of a randomized tobacco trial of ATD, the TRAb level was significantly higher in smokers than in nonsmokers [9–11]. Smoking promotes elevated levels of TRAb contributed to the development of GD. A number of factors recognized against GD includes stress, sex and sex hormones, pregnancy, infection, other autoimmune diseases, iodine and other potential environmental factors such as radiation have been recognized against Graves' Disease. The resulting breakdown in thyroid tolerance would lead to errors in multiple protective immune mechanisms. It is noted that sera of Graves's patients may contain the "predominant Hashimoto" thyroglobulin (Tg) and thyroid peroxidase antibodies (TPO Abs). Antibodies toward Hashimoto bind to the TSH receptor while, rather than promoting TSH action, block the growth of TSH action during illness and have seen positive results throughout the thyroid condition of Graves' Disease [12].
