ESPE Abstracts

Background: The pathogenesis of hyperthyroidism varies greatly, with familial non-autoimmune autosomal dominant hyperthyroidism being a rare cause. In patients who are genetically related, thyrotoxicosis develops without the clinical features of autoimmunity. In this study, we present five family members with familial hyperthyroidism who have a confirmed mutation of p.Ser237Asn in the TSHR receptor.

Case Report: Our patient, a 13,5- year-old boy, presented with clinical symptoms that were characteristic for diagnosis, including tachycardia, weight loss, unexplained fatigue, muscle tremors, and advanced bone age. Also, abnormal laboratory results were observed [TSH <0,01 ulU/ml (¯); fT3 7,79pg/ml (¬); fT4 2,78ng/ml (¬); TPO 6,3 IU/ml (N); ATG 15,7 IU/ml (N); anti-TSH <0,3 (N)]. Increased vascular flow in the gland was noted on ultrasound. Treatment began four months ago, and consisted of MMI 0,5mg/kg/day, which he is still taking, and β- blocker 0,5mg/kg/day. No adverse effects were observed. His mother, a 36-year-old woman, was diagnosed in 2009 with non-autoimmune hyperthyroidism and has been treated with radioactive iodine since. Family history of hyperthryoidism was noted in both her sister and mother. The grandmother of our patient was initially diagnosed and treated with thyroid therapy at the age of 42, followed by radioiodine therapy, which resulted in her developing hypothyroidism. The boy’s aunt received a thyroidectomy following an ineffective pharmacological treatment, and also currently presents with hypothyroidism. One of her daughters, although currently in good health, has a pathogenic mutation. Searching for the genetic basis of hyperthyroidism, blood was taken from the family members and sent to the Biomedicine Department of the University of Turku. A new mutation, p.Ser237Asn, was identified activating at the thyrotropin receptor in all family members, causing the overproduction of thyroid hormones and causing associated clinical features.

Conclusion: In patients who have developed non-autoimmune hyperthyroidism, deepened genetic history should be investigated, along with performing proper tests to possibly identify a gene mutation in the TSHR receptor. Proper radical therapy can be started following a correct diagnosis.