ESPE Abstracts (2019) 92 P1-148

Activating Mutation M453V in Receptor TSHR as a Cause Familial Hyperthyroidism

Beata Sawicka1, Alexandra Stephenson2, Hanna Borysewicz- Sanczyk1, Justyna Michalak1, Karolina Stozek1, Diana Tanja3, George Kahaly3, Ralf Paschke2, Artur Bossowski1


1Department of Pediatrics, Endocrinology, Diabetology, with Cardiology Division. Medical University in Białystok, Białystok, Poland. 2Division of Endocrinology and Metabolism Zone, Departments of Medicine, Oncology, Pathology & Laboratory Medicine, and Biochemistry and Molecular Biology. University of Calgary, Calgary, Canada. 3Molecular Thyroid Research Laboratory. Johannes Gutenberg University, Mainz, Germany


The most common hyperthyroidism in children is Graves' disease. The other rare cause of hyperthyroidism is activating mutation in receptor TSHR in thyroid gland.

We would like to introduce a case of familial hyperthyroidism with a novel mutation M453V in the TSHR in three members

Actually 11-year-old boy is a patient in outpatient clinic for first days after birth. During gestation his mother was treated with thyreostatic drugs because of Graves's disease. In newborn we diagnosed hypothyroidism and started therapy with l-thyroxin. Because of rapid normalisation of TSH, low levels of his antithyroid antibodises and normal thyroid gland by ultrasonography we finished his therapy with l-thyroxin when he was 6 months. When he was 3 years, he lost his body mass, he had tachycardia and advanced bone age (7 years). In laboratory labs TSH was decreased, elevated free thyroid hormones, with normal level of anti-thyroid antibodies. In ultrasonography thyroid tissue was with excessive flow.We diagnosed hyperthyroidism and we started treatment with taking methamizol, beta- blocker. We had not observed any side effects connected with the anti-thyroid therapy.The tests of stopped that therapy were ineffective and now we make a plan the radical therapy.

His actually 40-yrs-old mother was diagnosed Graves' disease when she was 6 years. She started the typical therapy of hyperthyroidism. She had positive family history with Graves' disease (her father and her 2 siblings). Because of ineffective drug therapy, she had strumectomy at 12-yrs aged. Because of recurrence of hyperthyroidism and presenting enlarged multinodular goitre pressing trachea in ultrasonography, she had the second strumectomy, when she was 30 years old. After surgery she had radioiodine therapy to eliminate thyroid tissue. In effect now she has hypothyroidism and she is administered with l-thyroxin.

Her younger son, who was born after second strumectomy, was admitted to our outpatient clinic when he was 6 years because of hyperthyroidism and we started appropriate therapy.

In order to find genetic basic of familial hyperthyroidism in mother and her children we identified a novel activating mutation M453V in receptor TSHR(heterozygous c.1357A>G), which initiates excessive production thyroid hormones and hyperthyroidism.

To summary, in case of familial hyperthyroidism it is worth to find and identify mutation in genes in receptor THSR, which may determinate risk assessment of hyperthyroidism and may use earlier appropriate therapy. The patients with activating mutation in receptor TSHR often need radical therapy, because long term therapy with thyreostatic drugs is ineffective

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