**1.1. Clinical features**

Clinical manifestations of the thyrotoxicosis are similar for various causes of thyrotoxicosis. However certain features provide some clues about specific cause of throtoxicosis. These features include the duration and mode of onset of thyrotoxicosis, size and shape of the thyroid gland, presence or absence of the extra-thyroidal manifestations like Graves' eye sign, pre-tibial myxoedema, acropachy. Patient presenting with toxic features can be because of thyroiditis or Graves' disease, but the symptoms are of few weeks duration in former while in later condition, it is for several months, most of the time. The common clinical features of thyrotoxicosis are listed below in table 2.

© 2012 Agrawal et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

	- a. Primary Hyperthyroidism
		- i. Graves' Disease
		- ii. Toxic Thyroid adenoma
		- iii. Toxic Multinodular Goiter
		- iv. Metastases from Thyroid carcinoma
		- v. Mutations of TSH receptor, Gsα (Mc Cune Albright Syndrome)

Thyroid Hormone Excess: Graves' Disease 161

England, in 1825.2 Carl A. Von Basedow from Germany first described the triad of exophthalmos, goiter and palpitation.3 In most non English speaking European countries the

Graves' disease is the most common cause of thyrotoxicosis and it accounts for 60-80% cases of thyrotoxicosis. Prevalence of Graves' disease varies with the degree of iodine sufficiency, and it is the most common cause of thyrotoxicosis in iodine sufficient countries.4 High dietary iodine intake is associated with an increased prevalence of Graves' disease. Prevalence of Graves' disease is about 0.4% in USA,5 0.6% in Italy,6 and 1.1% in UK.7 A recent meta-analysis of various studies showed that prevalence of the Graves' disease is about 1% in general population.7 Prevalence of Graves' disease is 1-2% in women, and it is about 10 fold more prevalent in women than men. Peak age of onset of Graves' disease is in

Graves' disease is a multifactorial disease in which genetic ,environmental, and hormonal

High prevalence of Graves' disease in family members and relatives of Graves' disease and Hashimoto's thyroiditis support that genetic factors are involved in causation of Graves' disease. There is also evidence that occurrence rate of Graves' disease is higher in monozygotic twins than dizygotic twins. The concordance rate in monozygotic twins is only

Graves' disease is a polygenic disease. Polymorphism in HLA-DR, CTLA-4 and PTPN-22 genes are associated with increased risk of Graves' disease. HLA-DR3 (HLA-DRB1\*03), HLA-DQA1\*0501 and HLA-B8 gives a risk ratio of three fold to fourfold in white population. HLA-DQ3 is involved in patients with African descent whereas HLA-BW46 is involved in patients with Asian descent. The other genes involved in pathogenesis of Graves' disease are CD40 gene, thyroglobulin gene, TSHR gene, immunoglobulin genes, GD-1 gene (on chromosome 14q13), GD-2 gene (on chromosome 20) and GD-3 gene (on

From very early it has been suggested that Graves' disease is associated with infectious agents, but this hypothesis has not been confirmed. Incidence of recent viral infections are high in patients with Graves' disease. The association of Graves' disease with infectious

fourth to sixth decade of life,8 but it can occur in children and elderly.

disease is still known as Basedow's disease.

**2.3. Risk Factors for Graves' disease** 

*2.3.1. Genetic factors for Graves' disease* 

17-35% which indicate low penentrance of genes.

*2.3.2. Environmental Factors for Graves' disease* 

**2.2. Epidemiology** 

factors play their role.

chromosome Xq21-22).

*Infection* 

	- i. TSH secreting pituitary tumours
	- ii. Pituitary Thyroid hormone resistance
	- a. Throiditis: subacute, silent
		- b. Ingestion of thyroid tissue, thyroid hormone
		- c. Thyroid gland destruction by amiodarone, radiotherapy, infarction in thyroid adenoma

**Table 1.** Causes of thyroid hormone excess


**Table 2.** Common clinical features
