Paediatrics: Graves’s disease

Graves’s disease

Graves’s disease is an autoimmune disorder with genetic and environmen-tal factors contributing to susceptibility. Several HLA-DR gene loci (DR3; DQA1*0501) have been identified as susceptibility loci and there is often a family history of autoimmune thyroid disease (girls > boys). Graves’s disease occurs due to a predominance of stimulating type autoantibodies to the TSH receptor.

Clinical features

In addition to those of hyperthyroidism, Graves’s disease is characterized by specific features:

·  Diffuse goitre (majority).

·  Graves’s ophthalmopathy: exophthalmos/proptosis; eyelid lag or retraction; periorbital oedema/chemosis; ophthalmoplegia/extraocular muscle dysfunction.

Diagnosis

Clinical suspicion of Graves’s disease requires confirmatory blood test:

·  Thyroid function tests: high T4/high T3/low TSH.

·  Thyroid antibody screen: antithyroid peroxidase; anti-thyroglobulin +ve; TSH receptor antibody (stimulatory type) +ve; radionucleotide thyroid scan—increased uptake.

Treatment

The aims of therapy are to induce remission of Graves’s disease with anti-thyroid drugs (carbimazole or propylthiouracil) and, if necessary, to bring the symptoms of thyrotoxicosis (anxiety, tremor, tachycardia) under con-trol using a B-blocking agent (propranolol). Two alternative regimens are practised.

·  Dose titration regimen: antithyroid treatment titrated to achieve normal thyroid function.

·  Block and replace regimen: antithyroid treatment maintained at the lowest dose necessary to induce complete thyroid suppression and therapeutic hypothyroidism. In this situation replacement thyroxine therapy is also necessary to achieve euthyroidism.

Antithyroid therapy is usually given for 12–24mths in children, before con-sidering a trial off treatment. Thyroid function (serum-free T4; TSH levels) should be monitored at regular intervals (1–3mths).

Prognosis

Following completion of treatment 40–75% of children will relapse over the next 2yrs. Relapses may be treated with a further course of antithyroid drugs, although definitive therapy with radioiodine is being offered as the first-line treatment. Thyroid surgery is another approach for management of relapses. Following ablative treatment (either radioiodine or surgery), lifelong thyroxine replacement therapy will be required.

Neonatal thyrotoxicosis

·Rare and due to the passive transfer of maternal thyroid antibodies from a thyrotoxic mother to the foetus.

·Affected neonates are irritable, flushed, and tachycardic. Weight gain is poor and cardiac failure may be present.

·The condition is self-limiting. Supportive treatment, e.g. beta blocker therapy, is required.