Case reports of familial non-autoimmune hyperthyroidism in two Malaysian families due to germline-activating mutations in the thyrotropin receptor gene

• Published in: US Endocrinology
• Main Author: Nor N.S.M.; Ling W.L.; Ali J.M.
• Format: Article
• Language: English
• Published: Touch Briefings 2020
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85086118515&doi=10.17925%2fuse.2020.16.1.42&partnerID=40&md5=d3814ed6955022d07764e952230b6645

Hyperthyroidism occurs less commonly than hypothyroidism in children. Hyperthyroidism in children is mostly due to autoimmunity, predominantly as a result of Graves' disease. Non-autoimmune hyperthyroidism (NAH), caused by activating mutations in the thyroid-stimulating hormone receptor (TSHR) gene, on the other hand, is a rare etiology for hyperthyroidism. The present study is the first to describe two unrelated families with NAH from Malaysia. The patients presented with signs and symptoms of hyperthyroidism, without evidence of autoimmunity. Mutation analysis was performed by direct DNA sequencing of all TSHR coding exons and this revealed heterozygous-activating mutations S505R and L629F. We noted the affected family members harboring the same mutation exhibited variable phenotypes, with regards to the age of onset and severity of hyperthyroidism. It is important to be observant of the presentation and natural history of genetic hyperthyroidism. Clinicians need to be aware of any deviation from the most typical features of Graves' disease, especially the lacking of autoimmune feature. An accurate diagnosis will provide patients with the most favorable outcome. © 2019, Touch Briefings.