**1. Introduction**

Graves' Disease (GD) is an autoimmune disease caused by autoantibodies against thyroid stimulating hormone receptor (TSH-R), resulting in stimulation of thyroid gland and overproduction of thyroid hormones resulting in clinical manifestations. GD is a relatively uncommon entity in pediatric age group, in contrast to adults, where prevalence ranges from 0.5–1%. Pediatric GD in the age group 0–15 years comprises of only 5–6% of the total number of Graves' thyrotoxic patients. It usually occurs in the context of a family history of autoimmune thyroid disease or in association with other autoimmune diseases like type 1 diabetes, Hashimoto's thyroiditis, rheumatoid arthritis or adrenal insufficiency. It is also found in association with

genetic syndromes like Down's syndrome and Turner's syndrome. However, GD is the most common cause of thyrotoxicosis in children, accounting for atleast 95% cases of hyperthyroidism and 10–15% of all childhood thyroid disorders [1]. Other rare causes of juvenile thyrotoxicosis include toxic adenoma (TA), toxic multinodular goitre (TMNG), McCune Albright syndrome (MAS), Hashimoto's thyroiditis and iatrogenic causes. In children, GD can occur at any age, but is most often diagnosed in adolescent age group, occurring more frequently in females than in males [2, 3].

The eye changes accompanying GD are termed thyroid-associated ophthalmopathy (TAO) or Graves' ophthalmopathy (GO). The symptoms of GO can run an independent course from the clinical course of thyrotoxicosis and often require specific treatment. Clinical characteristics of GO are often milder in children than in adults, nevertheless adversely affecting quality of life.

#### **2. Epidemiology**

Very few epidemiological studies are available to document the incidence of pediatric Graves' Disease in different populations, mostly involving Northern Europe and Hongkong. These have resulted in widely variable incidence rates, ranging from 0.79 to 6.5/100000 patient-years [4–9]. Iodine intake in populations could be one of the factors for differences observed in different populations, with higher incidence rates being observed in populations with higher iodine intake, particularly in studies from Hong-Kong compared to Caucasian children [7, 8].

GD, in concordance with other autoimmune disorders, is more common in females, particularly after 4 years of age. Female to male ratio has varied from 2.37–9.7 in various studies, depending on the age groups included [9]. The female preponderance becomes particularly marked in adolescent years, merging into the adult trends.

In one of the earliest nation-wide comprehensive studies, the incidence ratio of thyrotoxicosis was 0.79/100 000 person-years in Danish children under the age of 15 years between 1982 and 1988. The incidence was very low in age < 4 years, gradually increasing in both genders to peak incidence at 10–14 years of age. As with other autoimmune disorders, there was a female preponderance of 6.7: 1, but this difference was virtually non-existent in age group 0–4 years. The gender disparity widened gradually after early childhood to reach the maximum in the 10–14 year age group. Diffuse toxic goitre accounted for 96% of the cases, toxic adenoma and toxic multi-nodular goitre (MNG) were rare entities [4].

However, a more recent study in the Danish population spanning between 1998 and 2012 revealed a higher incidence rate of 1.58/100000 person-years [6], GD accounting for 86.8% of the cases. This increasing trend was consistent with rising incidences of other autoimmune disorders like type 1 diabetes and celiac disease. The authors postulated that environmental factors, including hygiene hypothesis, could play a key role in explaining the increasing trends in autoimmune disorders [6].

Similar trends of rising incidence rates have also been documented in studies from Hong-Kong as well. This could not be explained by the slight advancement in pubertal age or increasing disease awareness. The trends were primarily ascribed to the increasing iodine intake in the population, reflected by high urinary iodine concentration in the population [7, 8].

Similar to GD, GO is rare in pediatric age group. One of the earliest data about the incidence of pediatric GO came from the Olmsted County cohort study from Minnesota, USA. The study identified 120 incident cases of GO from 1976 to 1990. Peak incidence of GO had a bimodal distribution in the age groups 40–49 year and 60–69 years in both females and males, with a 5 year later presentation in males. The overall age-adjusted incidence rates per 100000 population were 16 and 2.9

#### *Graves' Disease in Childhood DOI: http://dx.doi.org/10.5772/intechopen.97569*

cases in females and males respectively. On the other hand, GO was much less frequent in the pediatric age group. Incidence rates per 100000 population per year in the age groups 5–9, 10–14, and 15–19 years were 3.5, 1.8 and 3.3 and 0, 1.7 and 0, for females and males respectively. Only 6 out of the 120 incident cases of GO observed in this cohort study were in patients below the age of 20 years [10]. The prevalence of GO in different countries has also been seen to be directly related to the prevalence of smoking in teenage population in the respective countries, emphasising the importance of smoking as risk factor for development of GO [11].
