Takahashi Sawako, Nishihara Eijun, Fukata Shuji, Miyauchi Akira, Akamizu Takashi
Center for Excellence in Thyroid Care, Kuma Hospital, Kobe 650-0011, Japan.
JCEM Case Rep. 2024 Sep 18;2(10):luae167. doi: 10.1210/jcemcr/luae167. eCollection 2024 Oct.
Familial nonautoimmune hyperthyroidism (NAH) is a rare type of autosomal dominant hyperthyroidism caused by constitutively active pathogenic variants of the thyrotropin receptor () gene. Although affected family members present with varied levels of hyperthyroid features, even when the same pathogenic variant is present, total thyroidectomy followed by radioiodine therapy is recommended for long-term management. Herein, we present the case of an 18-year-old proband and her family members with NAH (TSHR-I640V), who presented with diverse thyroid dysfunctions: fluctuations between euthyroid and subclinical hyperthyroidism, mild hyperthyroidism, and overt hyperthyroidism. Almost all affected adult family members, except the proband, showed no progression of hyperthyroidism or thyroid enlargement. A family history of thyrotropin receptor antibodies (TRAb)-negative hyperthyroidism is important for the identification of NAH in adults before genetic testing can be performed. Ablative therapy is not necessary when familial NAH presents with late-onset mild hyperthyroidism without coexisting diseases.
家族性非自身免疫性甲状腺功能亢进症（NAH）是一种罕见的常染色体显性甲状腺功能亢进症，由促甲状腺激素受体（TSHR）基因的组成型活性致病变体引起。尽管受影响的家庭成员表现出不同程度的甲状腺功能亢进特征，即使存在相同的致病变体，仍建议进行全甲状腺切除术后再行放射性碘治疗以进行长期管理。在此，我们报告了一例18岁的先证者及其患有NAH（TSHR-I640V）的家庭成员，他们表现出多种甲状腺功能障碍：甲状腺功能正常与亚临床甲状腺功能亢进、轻度甲状腺功能亢进和显性甲状腺功能亢进之间的波动。几乎所有受影响的成年家庭成员，除了先证者，均未出现甲状腺功能亢进进展或甲状腺肿大。在进行基因检测之前，促甲状腺激素受体抗体（TRAb）阴性的甲状腺功能亢进家族史对于成人NAH的识别很重要。当家族性NAH表现为迟发性轻度甲状腺功能亢进且无合并症时，无需进行消融治疗。
