HYPERTHYROIDISM

Hyperthyroidism is very rare in children, almost always caused by Graves disease, though rare causes include toxic uninodular goiter (Plummer disease) or thyroid adenoma/carcinomas.

Graves' disease is clinically characterized by hyper­thyroidism and ophthalmopathy, with or without other complications.

Etiologically, Graves' disease is an autoimmune dis­order, associated with increased levels of thyrotropin receptor stimulating and blocking antibodies (TRsAb, TRaAb) and the balance between the two decides the course of disease. It is frequently associated with other autoimmune disorders with specific HLA types (B8, D3, DR3), e.g. Addison's disease, T1DM and myasthenia gravis. Ophthalmopathy is caused by antibodies shared between thyroid and eye muscles.

Clinically, less than 5% of cases with Graves disease are children, most common during adolescence and in females. Family history is often present. Childhood course is variable and less fulminant than in adults, presenting with:

• Failure to thrive, despite voracious appetite;

• Neurological features, e.g. emotional lability, tremors, poor attention span and school performance;

• Autonomic disturbances, e.g. tachycardia, hyper­tension, facial flushing, excessive sweating, etc.

• Firm, homogenous goiter, though it may be absent;

• Uncommon signs of ophthalmopathy, e.g. exo­phthalmos, lagophthalmos and infrequent blinking. Thyroid crisis/storm is rare in children but may

present with acute hyperthermia, severe tachycardia and rapidly developing coma. Severe or long-standing cases may also develop cardiac complications, e.g. cardiomegaly, congestive cardiac failure or arrhythmia. Diagnosis is based on: (a) elevated FT3/FT4 levels with low TSH levels, (b) presence of TRsAb, and (c) thyroid scan showing rapid concentration of radioiodine in thyroid. Thyroid scan also helps to differentiate Graves disease (#8593; uptake) from Hashimoto thyroiditis (uptake).

Management of these cases includes:

• Antithyroid drugs, e.g. Carbimazole or Methimazole (0.25-1.0 mg/kg/day q24hr), with doses tailored according to the response. Propylthiouracil is contraindicated in children due hepatotoxicity.

• Radioiodine (¹³¹I) may be used as initial choice in children gt;10 years. Most cases become euthyroid with single dose only, though post-radiation hypothyroidism is almost inevitable.

• Surgery (subtotal thyroidectomy) or radioablation is the last resort in refractory cases and should be considered only after euthyroid state has been achieved by medical treatment.

• Symptomatic therapy with #946;-blockers, e.g. propranolol (0.5-2.0 mg/kg/day q8hr) is advised in cases with marked sympathetic hyperactivity.

• Thyroid storm may be treated with steroids, pro­pranolol and antithyroid drugs along with supportive measures. Steroids inhibit peripheral conversion of T4 to T3.

Ophthalmopathy resolves with therapy though severe cases have been treated with steroids. All cases should be monitored clinically with periodic hormonal assays and TRsAb levels.

Neonatal Graves' disease is seen in ~2% babies of mothers with Graves disease due to placental transfer of TRsAb and presents with prematurity, intrauterine growth retardation, restless/ irritable baby, lack of weight gain, advanced bone age and cardiovascular signs of hyperthyroidism. These cases should be treated with #946;-blockers and Methimazole till remission, which is common by 3-4 months of age.

22.4