*7.2.4 Monitoring*

Patient has to be clinically monitored for signs and symptoms of hyperthyroidism as well as for development of hypothyroidism. Patients can experience an exacerbation in ophthalmopathy, which may require treatment with glucocorticoids.

Hypothyroidism is usually achieved at 1–3 months after an optimal dose of I-131, with occasional patients taking upto 6 months to achieve hypothyroidism. Thyroid function tests should be obtained 4 weeks after I-131, followed by periodic testing at 4–6 weeks till hypothyroidism is achieved, when thyroid hormone replacement can be initiated [22, 36].

#### *7.2.5 Contraindications*

RAI therapy is an absolute contraindication in children less than 5 years of age as per AT and French guidelines. The latter also mention it as a relative contraindication in pre-pubertal children. Japanese guidelines advocate "careful administration" in children younger than 18 years of age on account of risk of thyroid malignancy and gonadal injury post radiation.

RAI therapy can be considered in pediatric patients with GO in non-severe cases. The NO-SPEC severity classification and clinical activity score (CAS) have not been validated in pediatric population. RAI therapy may still be considered in the presence of more severe manifestations like corneal involvement, persistent lid retraction and chemosis with concomitant oral glucocorticoid therapy, beginning a day after RAI, and tapered over 1–3 months [22, 31, 36].

#### **7.3 Surgery**

Surgery should be considered in patients with large goitres, presence of compressive symptoms, coexisting differentiated thyroid cancer (DTC), patients wishing to achieve faster remission, patients who do not wish to use ATDs or have adverse effects or contraindications to use of ATDs. ATA guidelines recommend thyroidectomy in children younger than 5 years of age, in whom definitive therapy is indicated and have accessibility to surgical expertise.

The major limiting factor for choice of surgery as the modality is the access to a high volume thyroid surgeon, defined as performing more than 30 cervical endocrine procedures in a year. The surgical complication rates are inversely related to the annual number of procedures by the operating surgeon, rather than the training or surgical specialty per se. The centre should be capable of handling pediatric anesthestic challenges and post-operative intensive care requirements. In the presence of availability of expertise and infrastructure, surgery can be offered as equivalent to RAI therapy to the parents [18].

#### *7.3.1 Preparation*

Patient should be rendered euthyroid with medications prior to surgery (thionamides, inorganic iodide and beta blockers). Potassium iodide, containing 50 mg iodide/drop can be administered as 1–2 drops thrice a day, 7–10 days prior to surgery can alleviate thyrotoxicosis as well as decrease vascularity of the gland. Dexamethasone can also help in rapid control of thyrotoxicosis [22, 36].

#### *7.3.2 Procedure*

Total or a near-total thyroidectomy (with <3 g of residual thyroid tissue) are the procedures of choice for management of GD. Partial or subtotal thyroidectomies may result in recurrence rates of 10–15%. Intra-operative PTH monitoring can be valuable in predicting the occurrence of post-operative hypocalcemia.

#### *7.3.3 Complications*

Most common post-operative complications include transient hypoparathyroidism and recurrent laryngeal nerve palsy. These complications tend to occur at the rate of 10–20%, more frequent than in adults, and are particularly more common in younger children. Other severe complications like permanent hypoparathyroidism, hematoma, infection, recurrent laryngeal nerve palsy occur less

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

frequently. Significant bleeding occurs more frequently with large goitres, necessitating blood transfusions in children. Caution has to be exercised in handling of recurrent laryngeal nerves as they are thinner in children. Growth-related bone metabolism may make the patient prone for transient hypoparathyroidism postoperatively. Post-operative hypocalcemia requiring intravenous calcium correction occurs more frequently in children. Its risk can be decreased by preoperative calcitriol, usually started 3 days before surgery and weaned off over the first 2 weeks post-operatively.

Surgery offers the advantages of definitive therapy. This has to be weighed against the risks associated with an invasive procedure, and the requirement of lifelong thyroxine replacement with appropriate monitoring after surgery [22, 31, 36].

## **7.4 Choice of modality**

Anti-thyroid drugs are usually the first line of management, typically administered for atleast 1–2 years. Definitive therapy with RAI therapy or surgery should be considered if remission is not attained after 1–2 years of ATD therapy. Continued medical management with periodic biochemical monitoring is a viable option in patients who are not candidates for either of the two definitive modalities. They offer the advantages of ease of administration, availability, reasonable safety and avoidance of exposure to radioactivity and surgical procedure. These have to be weighed against long duration of therapy and associated followup, lower rates of remission, low rates of compliance, higher frequency of adverse effects.

Radioiodine therapy in sufficient doses results in achievement of hypothyroidism in majority of patients, and should be considered as the modality of choice for definitive therapy in children >10 years of age, and in children 5–10 years of age with calculated dose requirements of less than 10 mCi. This has to be balanced against the risks of temporary flare, radiation thyroiditis and concerns of malignancy, even if theoretical as per most studies.


#### *Graves' Disease*

Surgery offers immediate and definitive therapy. However, the need for hospitalization, associated complications, surgical scarring preclude its use as a first line therapy. It can be considered in patients requiring definitive therapy and not being suitable candidates for RAI ablation.

Clinical factors that can influence the choice of modality are summarized in **Table 5**.

#### **8. Special considerations**

#### **8.1 Thyroid storm**

Encephalopathy can occur in association with thyroid storm. Initial presentation can include mental status changes including behavioural abnormalities, agitation, confusion, anxiety and emotional lability. Patients can also present with seizures, which can range from generalized tonic clonic to complex partial to more focal seizures.

#### **8.2 Neonatal GD**

Neonatal GD, though rare, can be life-threatening with significant morbidity and mortality. Maternal transfer of thyroid-stimulating immunoglobulins (TSIs) to the fetus, can occur in 1 in 80 cases of maternal GD. The risk of neonatal GD is directly proportional to the magnitude of elevation of TSI levels, typically increased at levels 2–4 times the upper limit of normal. The fetal thyroid can respond to TSIs resulting in excessive production of thyroid hormones.

This can manifest as fetal thyrotoxicosis, especially in second half of gestation. The condition should be suspected in the presence of fetal tachycardia (heart rate > 160/min after 20 weeks of gestation), goitre on antenatal ultrasound. Uncontrolled fetal thyrotoxicosis can result in intrauterine growth retardation (IUGR), premature fusion of cranial sutures, advanced skeletal age, accelerated maturation of femoral ossification centre, learning disabilities and mental retardation.

Management consists of adequate control of maternal thyrotoxicosis with anti-thyroid drugs. Propylthiouracil (PTU) is often the first choice at the time of organogenesis. Methimazole (MMI) is avoided in first trimester due to risk of methimazole embryopathy (Odds ratio of 1.66 for developing birth defects). This can manifest as aplasia cutis congenita, omphalocele, choanal and esophageal atresia and other omphalomesenteric duct anomalies in the newborn [52, 53].

The condition usually resolves by 3–6 months of age, due to clearance of TSIs from the infant's circulation. Infants may meanwhile require medical management of thyrotoxicosis. This entails treatment with antithyroid medications (PTU 5–10 mg/kg/day or MMI 0.5–1 mg/kg/day) and propranolol (1 mg/kg/day). Rapid biochemical control may require administration of Lugol's solution or saturated solution of potassium iodide (SSKI) for 7–10 days. Thyroid hormones typically normalize after 2 weeks of medical therapy, and may necessitate addition of levothyroxine to prevent hypothyroidism. Anti-thyroid medication can usually be weaned by 3 months, guided by monitoring of infant's serum TSI levels.

#### **9. Summary**

Graves' Disease in children is a classic example of children not being small adults. There are differences in management and response to treatment in children with Graves' Disease. Nuances exist for the various modalities for children and requires

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

specialist pediatric endocrinology care. Therapeutic options need to be discussed with parents before deciding on choice of definitive therapy. Smooth transitioning to adult endocrinology clinic is important to continue quality medical care.
