PDF(Pubmed)
Abstract：
Congenital hypothyroidism (CH) is a common heterogeneous endocrine disorder. The thyroid-stimulating hormone receptor gene (TSHR) is one of the major candidate genes associated with CH. Studies have investigated the possible correlations between the specific clinical features and the presence of TSHR variants. However, only a few reports have focused on the long-term follow-up of patients with CH. Here we present a case of CH-associated TSHR p.Arg109Gln and p.Arg450His rare compound heterozygous variants, with a follow-up performed until adolescence. The patient had high serum TSH levels during newborn screening. Oral administration of levothyroxine (l-T4) was initiated at 1 month of age. The ultrasonogram revealed normal thyroid morphology and blood flow. Reduced uptake of I-123 and negative perchlorate test was observed. A small amount of l-T4 remained needed although l-T4 could be steadily reduced by puberty. The patient was diagnosed with orthotopic, nongoitrous, and permanent CH. He had no nonclassical TSH resistance. Patients with the TSHR p.Arg109Gln compound heterozygous variant exhibit permanent CH with high TSH levels and normal or slightly lower fT4 levels. In the future, genotype identification could help predict the long-term prognosis and reduce the requirement for detailed examinations. More case studies are needed to determine the relationship between genetic variants and clinical features in CH.
摘要：
先天性甲状腺功能减退症（CH）是一种常见的异质性内分泌疾病。促甲状腺激素受体基因(TSHR)是与CH相关的主要候选基因之一。研究已经调查了特定临床特征与TSHR变体的存在之间的可能相关性。然而,只有少数报道关注CH患者的长期随访.在这里，我们介绍了一个与CH相关的TSHRp.Arg109Gln和p.Arg450His罕见的复合杂合变体，随访到青春期。患者在新生儿筛查期间血清TSH水平较高。在1月龄时开始口服左旋甲状腺素(l-T4)。超声显示甲状腺形态和血流正常。观察到I-123的摄取减少和高氯酸盐阴性试验。尽管青春期可以稳定地减少l-T4，但仍需要少量的l-T4。病人被诊断为原位，非甲状腺肿,永久CH。他没有非经典的TSH抗性。具有TSHRp.Arg109Gln复合杂合变体的患者表现出具有高TSH水平和正常或略低的fT4水平的永久性CH。在未来,基因型鉴定有助于预测长期预后,减少对详细检查的需求.需要更多的案例研究来确定CH的遗传变异与临床特征之间的关系。
