2nd Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Thyroid. 2010 Mar;20(3):327-32. doi: 10.1089/thy.2009.0182.
Germline activating mutations of the thyrotropin receptor (TSHR) gene have been considered as the only known cause of sporadic nonautoimmune hyperthyroidism in the pediatric population. Here we describe the long-term follow-up and evaluation of a patient with sporadic nonautoimmune primary hyperthyroidism who was found to have a de novo germline activating mutation of the TSHR gene.
The patient was an infant who presented at the age of 10 months in an unconscious state with exsiccation, wet skin, fever, and tachycardia. Nonautoimmune primary hyperthyroidism was diagnosed, and brain magnetic resonance imaging and computed tomography showed also Arnold-Chiari malformation type I. Continuous propylthiouracil treatment resulted in a prolonged clinical cure lasting for 10 years. At the age of 11 years and 5 months the patient underwent subtotal thyroidectomy because of symptoms of trachea compression caused by a progressive multinodular goiter. However, 2 months after surgery, hormonal evaluation indicated recurrent hyperthyroidism and the patient was treated with propylthiouracil during the next 4 years. At the age of 15 years the patient again developed symptoms of trachea compression. Radioiodine treatment resulted in a regression of the recurrent goiter and a permanent cure of hyperthyroidism without relapse during the last 3 years of his follow-up. Sequencing of exon 10 of the TSHR gene showed a de novo heterozygous germline I630L mutation, which has been previously described as activating mutation at somatic level in toxic thyroid nodules.
The I630L mutation of the TSHR gene occurs not only at somatic level in toxic thyroid nodules, but also its presence in germline is associated with nonautoimmune primary hyperthyroidism. Our case report demonstrates that in this disorder a continuous growth of the thyroid occurs without any evidence of elevated TSH due to antithyroid drug overdosing. This may justify previous recommendations for early treatment of affected patients with removal of as much thyroid tissue as possible.
促甲状腺素受体（TSHR）基因的种系激活突变被认为是儿科散发性非自身免疫性甲亢的唯一已知原因。在这里，我们描述了一位患有散发性非自身免疫性原发性甲亢的患者的长期随访和评估，该患者发现 TSHR 基因存在新生种系激活突变。
患者为 10 月龄婴儿，表现为昏迷状态，伴有干燥、皮肤湿润、发热和心动过速。诊断为非自身免疫性原发性甲亢，脑磁共振成像和计算机断层扫描也显示为第一型 Arnold-Chiari 畸形。连续丙硫氧嘧啶治疗导致长达 10 年的临床治愈。11 岁零 5 个月时，由于进行性多结节性甲状腺肿引起的气管压迫症状，患者接受了甲状腺次全切除术。然而，手术后 2 个月，激素评估表明出现复发性甲亢，患者在接下来的 4 年中接受丙硫氧嘧啶治疗。15 岁时，患者再次出现气管压迫症状。放射性碘治疗导致复发性甲状腺肿消退，甲亢永久性治愈，在过去 3 年的随访中无复发。TSHR 基因外显子 10 的测序显示存在新生杂合 I630L 突变，该突变以前在毒性甲状腺结节的体细胞水平被描述为激活突变。
TSHR 基因的 I630L 突变不仅发生在毒性甲状腺结节的体细胞水平，而且其在种系中的存在也与非自身免疫性原发性甲亢有关。我们的病例报告表明，在这种疾病中，甲状腺持续生长，而由于抗甲状腺药物过量，没有任何证据表明 TSH 升高。这可能证明了之前的建议，即对于患有这种疾病的患者，应尽早进行治疗，尽可能切除更多的甲状腺组织。
