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Graves Disease in Children

by Dr. Vera Oh



Graves disease has an incidence of 1:5000 and accounts for 95% of hyperthyroidism in children. Less common causes of thyrotoxicosis include chronic lymphocytic thyroiditis, subacute thyroiditis, thyroid adenomas, toxic nodular goitres and TSH-producing pituitary tumours.


As with most autoimmune conditions, there is a female preponderance among patients with Graves disease. The condition has a familial predisposition having been linked to human leukocyte antigen (HLA)-B8 and HLA-DR3. There is an association with Type 1 Diabetes Mellitus, systemic lupus erythematosus, rheumatoid arthritis, vitiligo, Addison’s disease and other immune-mediated conditions. Children with Trisomy 21 have a higher risk of Graves disease.






Patients typically present with a goitre, eye signs and symptoms of thyrotoxicosis. They may notice tremors, shakiness, sweatiness, weight loss, increased appetite, a rapid heartbeat, difficulty sleeping, fatigue, muscle weakness or heat intolerance. Inattention and emotional lability may cause difficulty in school. Patients may also complain of prominent or dry eyes. Adolescent girls may experience delayed puberty or secondary amenorrhoea. 




The goitre in Graves disease is diffusely enlarged, sometimes with an associated bruit. A thyroid nodule is not typical and the differential diagnosis of a thyroid adenoma needs to be entertained if there is one.  The characteristic eye signs of Graves ophthalmopathy may be present: proptosis, exophthalmos, lid lag, retraction or ophthalmoplegia. The patients may have a “stare-ry” look to them.


Thyroid hormone excess causes tachycardia, fine tremors, sweaty palms and other signs of sympathetic overdrive. Signs of pre-tibial myxedema described in adults are much rarer in children. 

A thyroid storm is a rare complication that manifests as sudden onset of fever, severe tachycardia, cardiac failure, confusion, drowsiness, delirium, coma and even death. This medical emergency can be triggered by trauma, surgery or infection.




Thyroid function tests demonstrate a raised fT4 and suppressed TSH. The presence of TSH receptor antibodies (TRAb) establishes the diagnosis of Graves disease. While thyroid peroxidise (TPO) or thyroglobulin (Tg ) antibodies may also be present, they are less sensitive and specific than TRAb. Imaging studies are usually unnecessary unless clinical findings suggest a nodule or are otherwise atypical.




Medical Management


In children, medical treatment is the first line of management. Carbimazole and propylthiouracil (PTU) are the main anti-thyroid drugs used. Beta blockers like propranol may be required to control the tachycardia. 

Because carbimazole has a longer half- life, it can be given once a day while PTU requires a thrice daily dosing. Carbimazole is usually started at an initial dose of 0.7mg/kg/day once or twice daily and then tailed down. PTU is given 5mg/kg/day in 3 divided doses. 


Similar adverse reactions may occur with both medications. Minor reactions like erythematous or urticarial rashes, arthalgia and transient granulocytopenia (ANC < 1500/mm3) occur in 10% of children. More severe reactions can occur in 2-5% of patients. Vasculitis, glomerulonephritis, agranulocytosis (ANC< 250/mm3), hepatitis and even hepatic failure have been reported. These tend to be hypersensitive reactions and occur anytime during treatment. With agranulocytosis, the risk is higher the first 3 months. There is increasing evidence that PTU is associated with a higher risk of liver injury than carbimazole so PTU should be reserved as a second line drug, used only in special circumstances.


With medical treatment, the remission rate is about 5-30% every 2 years. Favourable prognostication factors for remission are: a small goitre, lower levels of TRAb and pubertal status. A return of TRAb levels to normal augurs well for the likelihood of staying in remission when medication is stopped.


Unfortunately, 30% of patients who go into remission will relapse. The clinical situation then needs to be reassessed and another course of medical treatment or other options should be considered.




Surgical treatment or radioiodine are usually considered when medical management has failed or when the patient has experienced adverse side effects while on anti-thyroid medication. 


Classically, a subtotal thyroidectomy or partial thyroidectomy was performed. But the high relapse rate of 20-40% has prompted some centres to move towards a total or near total thyroidectomy. 


All forms of thyroid surgery risk injury to the recurrent laryngeal nerve or the parathyroid glands. In addition, the patient needs to be in a euthyroid state before surgery in order to minimise the risk of developing a thyroid storm. 




With the availability of more reassuring safety information, radioiodine has gained popularity over the last few years. Radioactive iodine is dosed with an aim to completely ablate the thyroid gland, thereby reducing the risk of future thyroid neoplasia. Long term follow-up data has shown no adverse effects on fertility or cancer risk. This form of treatment can be considered in children over 10 years of age. Unlike their adult counterparts, children with Graves ophthalmopathy do not appear to have worsening of their eye condition after radioiodine. Nevertheless, radioiodine is used with caution in this group.   


While hypothyroidism is a complication of both surgery and radioiodine, it is a condition that is relatively straightforward and easy to treat. At the right doses, thyroxine has also fewer serious adverse effects than anti-thyroid medication.




Neonates may suffer from thyrotoxicosis secondary to transplacental transfer of stimulating maternal antibodies. The mothers may have a history of Graves or be as yet undiagnosed. 


The condition is transient as the maternal antibodies are cleared from the baby’s system by 12 weeks. Although rare, this condition has a high mortality rate of approximately 20%. Babies with neonatal thyrotoxicosis may have a low birth weight, microcephaly or craniosynostosis. Typically, they present a few days after birth with irritability, sweating, vomiting, diarrhoea, tachycardia, poor feeding or hyperthermia. There may be associated hepatomegaly, jaundice or signs of cardiac failure.


Management of this life-threatening condition is similar to treatment of a thyroid storm. The aims are:  Decreasing thyroid hormone production, reducing peripheral conversion of T4 to active T3, beta blockade and further supportive treatment. These are achieved with a combination of antithyroid medication (PTU is useful here), iodine, steroids and beta-blockers.


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