Congenital nonautoimmune hyperthyroidism in a nonidentical twin caused by a sporadic germline mutation in the thyrotropin receptor gene.
Congenital nonautoimmune hyperthyroidism in a nonidentical twin caused by a sporadic germline mutation in the thyrotropin receptor gene.
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异卵双胞胎中的先天性非自身免疫性甲状腺功能亢进症是由促甲状腺激素受体基因的偶发性种系突变引起的。
DOI：
10.1089/thy.1997.7.765
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Roe,TF
中科院分区：
文献类型：
--
作者：
Kopp,P;Jameson,JL;Roe,TF
先天性甲状腺功能亢进症通常是由患有自身免疫性甲状腺疾病的母亲的甲状腺刺激抗体转移到胎儿引起的。最近，在少数散发性非自身免疫性先天性甲状腺功能亢进症患者以及家族性非自身免疫性甲状腺功能亢进症患者中检测到促甲状腺激素（TSH）受体的生殖细胞突变，从而定义了一种新的甲状腺功能亢进症的病理生理学实体。在这份报告中，我们描述了一个异卵双胞胎女孩与严重的先天性甲状腺功能亢进症。双胞胎兄弟和母亲甲状腺功能正常。头颅X线片显示矢状缝过早骨性结合。甲状腺功能亢进症不能充分控制抗甲状腺药物和放射性碘治疗。在3岁时进行了几乎全甲状腺切除术后，患者出现甲状腺功能减退，需要甲状腺激素替代治疗。14岁时，甲状腺功能亢进症复发。手术切除了右上叶的增生残留物，导致甲状腺功能正常。在接下来的几年里，甲状腺激素水平逐渐升高，在19岁时，她再次甲状腺功能亢进。没有自身免疫过程的临床或生化证据。患者的神经发育受损，智力低于正常。TSH受体基因的直接测序揭示了一个杂合突变，导致第六跨膜段中苏氨酸632被异亮氨酸取代，这种氨基酸变化已知会导致环磷酸腺苷（cAMP）途径的组成性激活。该突变在父母和双胞胎兄弟中均不存在，表明为新种系突变。早期识别这种疾病是重要的，因为标准治疗的阻力，特殊的治疗意义，和家庭传播的可能性。
Congenital hyperthyroidism is usually caused by maternal-to-fetal transfer of thyroid-stimulating antibodies from a mother with autoimmune thyroid disease. Very recently, activating thyrotropin (TSH) receptor germline mutations were detected in a few patients with sporadic nonautoimmune congenital hyperthyroidism, as well as in familial forms of nonautoimmune hyperthyroidism defining a new pathophysiological entity of hyperthyroidism. In this report, we describe a nonidentical twin girl with severe congenital hyperthyroidism. The twin brother and the mother were euthyroid. Skull radiographs revealed premature synostosis of the sagittal sutures. Hyperthyroidism was inadequately controlled with antithyroid drugs and radioiodine therapy. After a near-total thyroidectomy performed at age 3, the patient became hypothyroid and required thyroid hormone replacement. At age 14, hyperthyroidism recurred. A hyperplastic remnant of the right upper lobe was removed surgically, resulting in euthyroidism. Over the following years, thyroid hormone levels increased gradually and at age 19 she was again hyperthyroid. There was no clinical or biochemical evidence of an autoimmune process. The patient's neurologic development was impaired and her intelligence is subnormal. Direct sequencing of the TSH receptor gene revealed a heterozygous mutation resulting in a substitution of threonine632by isoleucine in the sixth transmembrane segment, an amino acid change known to result in constitutive activation of the cyclic adenosine monophosphate (cAMP) pathway. The mutation was absent in the parents and the twin brother, indicating ade novogermline mutation. Early recognition of this disorder is important because of the resistance to standard treatment, special therapeutic implications, and the possibility of familial transmission.