Shiwa Tsuguka, Oki Kenji, Awaya Tomokazu, Nakanishi Shuhei, Yamane Kiminori
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
Intern Med. 2011;50(18):1977-80. doi: 10.2169/internalmedicine.50.4904. Epub 2011 Sep 15.
Resistance to thyroid hormone (RTH) is characterized by elevated serum levels of thyroid hormones and normal or slightly increased serum thyrotropin (TSH) levels. Recently it has been suggested that chronic TSH stimulation in RTH activates intrathyroidal lymphocytes, leading to thyroid damage and autoimmune thyroid disease (AITD). Therefore, individuals with RTH have an increased likelihood of AITD compared to unaffected relatives. We here report a 33-year-old woman in whom we diagnosed Graves' disease and treated her with thiamazole (MMI). For two years, her TSH levels were suppressed when thyroid hormones were elevated and conversely they were increased when thyroid hormones levels were decreased. These findings were common for a clinical course during treatment for Graves' disease with anti-thyroid drug. However, three years after the initiation of MMI therapy, she had a normal or gradually elevated serum TSH level even though the level of thyroid hormones never decreased, indicating inappropriate secretion of TSH. We concluded she had RTH clinically, and we demonstrated by direct sequence analysis a mutation of the TRβ gene, causing replacement of a glycine (G) with arginine (R) at codon 251. The finding of an elevated TSH level without decreased thyroid hormones should suggest the presence of RTH during therapy of Graves' disease.
甲状腺激素抵抗（RTH）的特征是血清甲状腺激素水平升高，而血清促甲状腺激素（TSH）水平正常或略有升高。最近有人提出，RTH中的慢性TSH刺激会激活甲状腺内淋巴细胞，导致甲状腺损伤和自身免疫性甲状腺疾病（AITD）。因此，与未受影响的亲属相比，RTH患者患AITD的可能性增加。我们在此报告一名33岁女性，我们诊断其患有格雷夫斯病并用甲巯咪唑（MMI）对其进行治疗。两年来，当甲状腺激素升高时她的TSH水平受到抑制，反之，当甲状腺激素水平降低时TSH水平则升高。这些发现在用抗甲状腺药物治疗格雷夫斯病的临床过程中很常见。然而，在开始MMI治疗三年后，即使甲状腺激素水平从未降低，但她的血清TSH水平正常或逐渐升高，表明TSH分泌异常。我们临床诊断她患有RTH，并通过直接序列分析证实TRβ基因发生突变，导致第251密码子处的甘氨酸（G）被精氨酸（R）取代。在格雷夫斯病治疗期间，TSH水平升高而甲状腺激素水平未降低的情况应提示存在RTH。
