CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
“Severe congenital hyperthyroidism caused by a germline mutation in the thyrotropin receptor gene (TSHR)”.
Autor/es:
SCAGLIA P.; CHIESA A; BASTIDA G.; PACIN M.; DOMENÉ H.; GRUÑEIRO-PAPENDIECK L
Lugar:
Praga, República Checa
Reunión:
Congreso; 49th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE).; 2010
Institución organizadora:
European Society for Paediatric Endocrinology (ESPE).
Resumen:
Activating mutations in the TSHR gene have been identified as the molecular basis for congenital non autoimmune hyperthyroidism. We describe the clinical findings and molecular characterization of an sporadic case of severe non autoimmune hyperthyroidism. A girl with hyperthyroidism and goiter was followed since 8 days of life when she presented TSH <0.01 mUl/l, T4 24.8 ìg/dl, T3 422 ng/dl,Trab <10%, and negative antiperoxidase antibodies and started treatment with metilmercaptoimidazol and b-blockers. She was the only daughter of a 30 year old mother with autoimmune hyperthyroidism treated before pregnancy with 131I. Pregnancy and delivery were uneventful and the mother remained euthyroid under thyroid hormone replacement with Trab<10 %. The girl persisted hyperthyroid with recurrence of hyperthyroidism when treatment was lowered. At 6.9 years, a total thyroidectomy was performed. Histology revealed follicular cell hyperplasia, without lymphocytic infiltration. With suspicion of an activating TSHR gene mutation, genomic DNA of mother and child was extracted from peripheral venous blood. The whole coding sequence of TSHR gene (10 exons and intron-exon boundaries) was PCR amplified and sequenced using specific primers. The patient presented a heterozygous G>A transition (AGC>AAC) in codon 281 (exon 9), resulting in S281N mutation in the extracellular domain of TSH receptor and a heterozygous C>G transversion in the third base of codon 727 (exon 10), resulting in D727E polymorphism. Mother analysis revealed a heterozygous G>A transition in codon 459 (GCG>GCA), resulting in a silent polymorphism (A459A). The S281N TSHR gene mutation has already been described both as germline and somatic activating mutation, and characterized by in vitro increase of basal production of cAMP. Although congenital non autoimmune hyperthyroidism is a rare condition, it should be investigated when severe disease persists, even in a newborn from an autoimmune hyperthyroid mother, in order to differentiate it from the more common congenital autoimmune disease. TSHR gene have been identified as the molecular basis for congenital non autoimmune hyperthyroidism. We describe the clinical findings and molecular characterization of an sporadic case of severe non autoimmune hyperthyroidism. A girl with hyperthyroidism and goiter was followed since 8 days of life when she presented TSH <0.01 mUl/l, T4 24.8 ìg/dl, T3 422 ng/dl,Trab <10%, and negative antiperoxidase antibodies and started treatment with metilmercaptoimidazol and b-blockers. She was the only daughter of a 30 year old mother with autoimmune hyperthyroidism treated before pregnancy with 131I. Pregnancy and delivery were uneventful and the mother remained euthyroid under thyroid hormone replacement with Trab<10 %. The girl persisted hyperthyroid with recurrence of hyperthyroidism when treatment was lowered. At 6.9 years, a total thyroidectomy was performed. Histology revealed follicular cell hyperplasia, without lymphocytic infiltration. With suspicion of an activating TSHR gene mutation, genomic DNA of mother and child was extracted from peripheral venous blood. The whole coding sequence of TSHR gene (10 exons and intron-exon boundaries) was PCR amplified and sequenced using specific primers. The patient presented a heterozygous G>A transition (AGC>AAC) in codon 281 (exon 9), resulting in S281N mutation in the extracellular domain of TSH receptor and a heterozygous C>G transversion in the third base of codon 727 (exon 10), resulting in D727E polymorphism. Mother analysis revealed a heterozygous G>A transition in codon 459 (GCG>GCA), resulting in a silent polymorphism (A459A). The S281N TSHR gene mutation has already been described both as germline and somatic activating mutation, and characterized by in vitro increase of basal production of cAMP. Although congenital non autoimmune hyperthyroidism is a rare condition, it should be investigated when severe disease persists, even in a newborn from an autoimmune hyperthyroid mother, in order to differentiate it from the more common congenital autoimmune disease.