Multiple relapses of hyperthyroidism in a patient with long term follow up of sporadic non-autoimmune hyperthyroidism

We report a male patient with neonatal non autoimmune hyperthyroidism due to an activating thyrotropin receptor (TSHR) germline mutation with multiple relapses despite repeated subtotal thyroidectomy.

The patient was born prematurely at 36 weeks of gestation by spontaneous delivery with a birth weight of 2400g and a length of 51cm. The patient's mother, father and brother were without a history of any thyroid disease. At the age of 45 days the infant developed persistent diarrhea, irritability and fever up to 38°C. Physical examination revealed exophthalmos, hypertelorismus, dolichocephaly, arachnodactyly, thyroid gland enlargement grade I, tachycardia (160 beats/min), systolic heart murmur grade 2/6, blood pressure 185/60mmHg. Scull x-ray revealed craniosynostosis. The bone age was advanced to 4 years. Treatment with antithyroid drugs was started at the age of six months. During the 21 years of follow-up the patient developed eight relapses of hyperthyroidism, four of them after dose reduction before the 1-st subtotal thyroidectomy at the age of 1.1 years, of 2 years, of 4.2 years and of 8.3 years respectively. The remission after the 1-st subtotal thyroidectomy lasted for one year after the 2-nd thyroid surgery for 6 years and after the following near total thyroidectomy it lasted for 10 months.

Sequencing of the TSHR gene revealed a gain-of-function mutation with an amino acid exchange of aspartate to tyrosin in codon 633 which is located in the sixth transmembrane domain of the receptor. The absence of the mutation in all other family members identifies the patient's TSHR mutation as a sporadic germline mutation. In our patient hyperthyroidism could repeatedly not be controlled by near total thyroidectomy. Therefore, early combined treatment with near-total thyroidectomy plus radioiodine therapy seems to be the treatment of choice for patients with sporadic non-autoimmune hyperthyroidism.