Background: Congenital hyperthyroidism is a rare disease. In most patients with congenital hyperthyroidism are autoimmune forms caused by maternal thyroid-stimulating antibodies. In contrast to autoimmune hyperthyroidism that is transient, nonautoimmune form of congenital hyperthyroidism is persistent and results from activating germline mutations in the thyrotropin receptor (TSHR) gene.
Case presentation: We report the case of a Korean male infant with severe nonautoimmune neonatal hyperthyroidism due to germline TSHR mutation (A633G). He was delivered by emergency Caesarian section from a mother without thyroid disease at 33 weeks of gestational age because of foetal tachycardia and premature rupture of membranes. He had persistent tachycardia at 24 days of life. Brain MRI revealed mild hydrocephalus with craniosynostosis. Echocardiography and electrocariography showed sinus tachycardia. Thyroid function tests was confirmed hyperthyroidism with T3 10.52 ng/ml (0.781.82), fT4 3.98 ng/dl (0.851.86), and TSH 0.05 mIU/l (0.174.05). Antibodies to TSHR, thyroid peroxidase (TPO) and thyroglobulin (TG) were negative. Thyroid ultrasonography showed increased vascularity and 2 mm sized hypoechoic nodule in right thyroid. Thyroid scan revealed diffusely increased uptake and goitre. He was started on propylthiouracil (PTU) and propranolol, but it was difficult to control hyperthyroidism. At the age of 3 months, craniosynostosis and hydrocephalus were aggravated. He underwent ventriculoperitoneal shunt operation. After 5 months of PTU treatment, thyroid function tests showed euthyroid state and tachycardia was resolved. PTU was changed to methimazole and after reducing the dose of methimazole, hyperthyroidism was relapsed. We increased the dose of methimazole again. In direct sequencing for whole exons including intron-exon boundaries of TSHR gene, a cytosine to adenine transition in exon 10 was identified. He was heterozygous for substitution of aspartate by glutamine at codon 633.
Conclusion: This is the first report of a nonautoimmune neonatal hyperthyroidism due to A633G mutation in the TSHR gene. Now, the molecular analysis of his parents TSHR gene are processing. If the patient has de novo heterozygous mutation of TSHR gene, it can be difficult to control hyperthyroidism using antithyroid drugs only rather than familial form. We should also consider the thyroidectomy or radioiodine treatment to prevent comorbidity of hyperthyroidism.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology