Longitudinal Evaluation of Patients with a Homozygous R450H Mutation of the TSH Receptor Gene
Longitudinal Evaluation of Patients with a Homozygous R450H Mutation of the TSH Receptor Gene
复制标题
TSH 受体基因纯合 R450H 突变患者的纵向评估
DOI：
10.1159/000223415
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发表时间：
2009
影响因子：
3.2
通讯作者：
K. Onigata
中科院分区：
文献类型：
--
作者：
H. Mizuno;Keisuke Kanda;Yukari Sugiyama;Hiroki Imamine;Tetsuya Ito;I. Kato;H. Togari;T. Kamoda;K. Onigata
背景/目的：TSH受体（TSHR）基因的R450 H突变在日本TSH耐药患者中经常观察到。本研究的目的是澄清TSHR基因纯合R450 H突变患者的表型;突变型受体先前已在体外表现出中度功能受损。研究方法：我们进行了一项临床调查的5名日本患者谁有高促甲状腺素血症的新生儿，其中TSHR基因的纯合R450 H突变已被证明通过基因测序分析。结果：婴儿早期甲状腺激素水平正常，血清TSH轻度升高。在开始用左旋甲状腺素钠（L-T4）补充治疗后，我们不得不增加剂量以维持所有患者的TSH水平在正常范围内。1例停服L-T4 1个月后复查时甲状腺功能明显异常。4例患者进行了智商检查，其得分均正常。结论：对于TSHR基因纯合子R450 H突变的高促甲状腺素血症患者，即使他们在婴儿期未表现出明显的甲状腺功能减退，也应根据其生物学数据考虑甲状腺激素替代治疗。
Background/Aim: The R450H mutation of the TSH receptor (TSHR) gene has been frequently observed in Japanese patients with resistance to TSH. The purpose of this study was to clarify the phenotype of patients with a homozygous R450H mutation of the TSHR gene; the mutant receptor has previously demonstrated moderately impaired function in vitro. Methods: We performed a clinical investigation of 5 Japanese patients who had hyperthyrotropinemia as neonates, in whom a homozygous R450H mutation of the TSHR gene had been demonstrated by genetic sequencing analysis. Results: The thyroid hormone levels of the patients were normal in early infancy, although their serum levels of TSH were mildly elevated. After supplemental treatment with levothyroxine sodium (L-T4) was started, we had to increase the dose to maintain the level of TSH within the normal range in all patients. Thyroid dysfunction became obvious in one patient at reexamination during adolescence when L-T4 treatment was stopped for 1 month. Four patients were examined for intelligence quotient and their scores were normal. Conclusions: Thyroid hormone replacement therapy should be considered based on biological data in patients with hyperthyrotropinemia who have a homozygous R450H mutation of the TSHR gene even if they do not exhibit obvious hypothyroidism in infancy.