Graves’ disease in a five-month-old boy with an unusual treatment course

Abstract

ObjectivesGraves’ disease (GD) is rare in children under age five years. Antithyroid drugs are typically first-line therapy but carry the risks of agranulocytosis and liver dysfunction.Case presentationA male infant with multiple congenital anomalies, left ventricular hypertrophy, and neurologic dysfunction developed GD at five months of life. The presence of chronic hepatitis complicated medical management. Potassium iodide was effective temporarily, but urgent thyroidectomy was required at nine months of age. Postoperatively, the patient developed a thyroid function pattern consistent with impaired pituitary sensitivity to thyroid hormone (TH) that responded to the addition of liothyronine. Exome sequencing revealed a heterozygous de novo duplication of the ATAD3 gene cluster, suggesting a possible mitochondrial disorder.ConclusionsThis case describes the youngest child to date to be diagnosed with endogenous GD and to successfully undergo definitive treatment with thyroidectomy. An underlying defect in mitochondrial function is suspected, suggesting a potential novel pathophysiologic link to early-onset thyroid autoimmunity. Additionally, this case illustrated the development of impaired pituitary sensitivity to TH following thyrotoxicosis of postnatal onset, which may contribute to our understanding of hypothalamic-pituitary-thyroid (HPT) axis development.

ATAD3A: A Key Regulator of Mitochondria-Associated Diseases

“…Azova et al identified a heterozygous de novo duplication of the ATAD3 gene cluster in a male infant with multiple congenital anomalies, left ventricular hypertrophy, and neurological dysfunction [51]. The infant developed endogenous Graves' disease at five months of age.…”

“…The infant developed endogenous Graves' disease at five months of age. Graves' disease is an autoimmune disease that can lead to hyperthyroidism characterized by excessive production of thyroid hormone and is uncommon in children under five years old [51,55]. Azova et al suspected a possible mitochondrial dysfunction that may potentially account for a novel pathophysiology for early-onset Graves' disease [51,56,57].…”