Cường giáp không liên quan đến cơ chế tự miễn do đột biến hoạt hóa gen TSHR: Báo cáo ca bệnh

Abstract

Non-autoimmune hyperthyroidism (NAH) is a rare disorder caused by activating mutations of the thyroid-stimulating hormone receptor (TSHR) gene. Current evidence on this disease is largely based on case reports and small series, reflecting the rarity of reported cases worldwide. We report the case of a 2-year-old girl who developed bilateral exophthalmos at 7 months of age, followed by tremor, tachycardia, and poor weight gain. Laboratory investigations revealed overt hyperthyroidism with a thyroid-stimulating hormone (TSH) level of < 0.005 mIU/L, free thyroxine (FT4) level > 100 pmol/L, and triiodothyronine (T3) level of 9.31 nmol/L, while thyroid autoantibodies were negative. Family history revealed multiple affected individuals with hyperthyroidism across successive generations, suggesting an autosomal dominant pattern of inheritance. Genetic analysis identified a heterozygous TSHR variant, c.1514G>A (p.Ser505Asn), which was classified as a likely pathogenic variant. The patient was treated with methimazole and propranolol and showed a favorable response, with improvement in thyroid function tests after 15 months of follow-up. This case highlights the importance of considering a genetic etiology in children presenting with early-onset hyperthyroidism, particularly in the presence of negative thyroid autoantibodies and a compatible family history.