Advanced Bone Age Present in a Neonatal Case of Sporadic Non-Autoimmune Hyperthyroidism Before Onset of Symptoms

Sporadic congenital non-autoimmune hyperthyroidism (SNAH) is rare. Several reported cases show that symptoms were present for at least 2–6 months before diagnosis, leading to premature bone aging. We report a case of SNAH for which the diagnosis of hyperthyroidism was established by chance prior to the onset of symptoms due to thyroxine treatment of the mother during pregnancy. In spite of early diagnosis at 4 months chronological age, an advanced bone age of 1.5 years was already present. Before the molecular diagnosis was established, the patient was treated with repeatedly increasing thiamazole doses. At 13 months of age, the patient had a further increase in thyroid gland volume and in bone age (2.5 years). Using high-resolution melting PCR followed by Sanger sequencing, a heterozygous T632I amino acid change was detected. This mutation has previously been functionally characterized as constitutively activating. Neither parent carries this mutation, so it is a sporadic germline mutation. Early diagnosis of SNAH is essential and challenging in a neonate. This case demonstrates that premature bone aging can be present even before the onset of hyperthyroidism symptoms. Detection of germline TSHR mutation for patients suspicious for SNAH is important to direct therapy, as non-autoimmune hyperthyroidism does not generally respond well to antithyroid drug treatment and surgical removal of the thyroid is necessary for these patients.