**4. Clinical features**

GD can present at any age, with peak prevalence occurring in adolescent years. Around 10% of cases can present in very young children less than 5 years of age. GD is clinically characterized by the triad of thyrotoxicosis, ophthalmopathy and dermopathy. GD in children often presents with classical symptoms and signs of thyrotoxicosis like in adults.

The frequency of the symptomatology, however, is variable across literature. Major presenting symptoms symptoms include goitre (19–99%), excessive sweating and heat intolerance (28–53%), fatigue or weakness (10–54%), irritability, nervousness or restlessness (17–47%), tremors (17–58%), ocular symptoms, ophthalmopathy or exophthalmos (10–43%), weight loss or no weight gain (28–63%), tachycardia (34–45%). Decreased academic performance can be seen in 1–24% of patients, whereas decreased athletic performance can be seen in upto 15% of patients. Other common complaints included behavioural changes (50%), headache (1–22%), increased bowel frequency (11–16%) and slight fever (10.5%) [5, 20–22]. Children can also present with ocular complaints like pain, foreign body sensation and grittiness, tearing, redness, photosensitivity, and rarely diplopia [23].

Children, like adults, can have low bone mass for age and increased fracture risk in the presence of untreated thyrotoxicosis, but this is often reversible once euthyroidism is restored for 2 years with treatment. Thyrotoxicosis may rarely be associated with choreiform movements in childhood and adolescence. This may manifest as involuntary, coordinated, rapid spastic movements like flexion and extension of fingers, raising and lowering of shoulders and grimacing. Thyrotoxicosis can also result in proximal muscle weakness and wasting syndrome, termed the thyrotoxic myopathy, which can mimic limb girdle muscular dystrophy. Importantly, these symptoms can even precede the more typical thyrotoxic symptoms. Another type of muscular weakness associated with thyrotoxicosis is thyrotoxic periodic paralysis,

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

characterized by recurrent transient episodes of muscular weakness, usually precipitated by a stressor event like exposure to cold, high carbohydrate meal, infections and stress. This phenomenon has been more commonly described in Asian populations in middle aged males. It is rare in pediatric age groups, and is virtually not reported in very young populations [24].

The symptomatology, clinical and biochemical severity are also a function of age of onset of disease. Prepubertal children tend to have a more severe disease, longer duration of complaints and higher thyroid hormone levels at presentation than the pubertal and postpubertal children. Prepubertal children tend to present with weight loss and bowel frequency, associated with accelerated growth and bone maturation. Older children are more likely to present with the classical symptoms of thyrotoxicosis like palpitations, tremors and heat intolerance [25].

The risk of developing GO in pediatric GD appears to be to be similar to or slightly higher than the risk in adult patients with GD. Female preponderance (87%) is also similar to that observed in adult patients (83%). However, pediatric GO tends to be less severe and debilitating as compared to adult manifestations. Soft tissue involvement, lid lag, proptosis and punctate corneal epithelial erosions are more commonly seen with pediatric GO, whereas the more severe manifestations like restricted ocular motility, severe strabismus and optic nerve affection are virtually never seen in pediatric GO. This has been attributed to the lower prevalence of smoking in children as compared to adults. Manifestations of GO tended to become similar to adults as adolescence approached in pediatric patients with GO in another study, likely due to increased prevalence of smoking in adolescent ages. Hence active or passive smoking seems to increase the risk and severity of GO in children as well as adults [11, 26, 27].

The non-specificity of some of the symptoms in pediatric age group can lead to children being initially seen by psychologists, gastroenterologists, neurologists, cardiologists and ophthalmologists, before being referred to endocrinology.

Examination may reveal tachycardia, increased blood pressure for age and raised pulse pressure. Skin may be warm and moist, thinning of hair, onycholysis and softening of nails can be present.Vitiligo and alopecia areata can be seen in patients with associated autoimmune disorders. Precordial pulsations may be prominent, accompanied by a apical systolic regurgitant murmur due to functional mitral insufficiency secondary to papillary muscle dysfunction. Tremors may be present, along with hyperactive deep tendon reflexes. Musculoskeletal examination may reveal proximal muscle weakness and wasting.

On local examination, size of the gland can be variable, with a large proportion of patients having none to small or moderate sized goitre, which may escape patient's and family's attention [28]. The thyroid gland is usually symmetrically enlarged, non-tender, smooth and having firm consistency, and may be associated with a palpable thrill and a thyroid bruit in upto one fourth of patients due to increased vascularity. A large goitre can cause tracheal compression and other compressive symptoms.

Lid retraction, especially of the upper eyelid, and a staring appearance may be evident in upto one-third of the cases. Lid retraction is a sign of adrenergic overactivity, and is not considered a sign of GO per se. Other common signs in pediatric GO are lagophthalmos or von Graefe's sign (9–74%), proptosis (4–91%), signs of soft tissue involvement (19–26%), including conjunctival injection (8–49%), chemosis (1–23%) and lid edema in around 10% of the patients. Corneal involvement can occur in the form of corneal punctate staining (12–34%), exposure keratitis and superior limbic keratitis. Extraocular muscle motility defects has been described in relatively fewer number of patients (2–11%), except in a study by Eha et al., where it was observed in 36% of the patients [23] (**Table 1**). Similarly, dysthyroid optic neuropathy (DON) can be seen very rarely in pediatric age groups.


#### **Table 1.**

*Differences in Pediatric vs. Adult Graves' Disease.*

Some of the key differences in the presentation of pediatric GD vis-à-vis adult GD are as follows:


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

growth charts. Increase in height SDS is seen more commonly in prepubertal children than pubertal and post-pubertal children. This may be explained by the fact that prepubertal bone maturation is driven by growth hormone (GH) and thyroid hormones, whereas pubertal bone growth is driven primarily by estradiol. Another plausible reason could be the delay in diagnosis in younger children. The effect on final height, however is variable across literature, where some studies show achievement of a normal height within target range, some showing increased final height [25, 29]


Pediatric GD can commonly be associated with other conditions as follows [2, 30].
