Igarashi Kouhei, Takita Chie, Matsumoto Masako, Kitagawa Wataru, Ota Atsuko, Miyazaki Naoko, Ito Koichi, Ikeda Kazutaka
Laboratory of Biomolecule Analysis, Department of Applied Genomics, Kazusa DNA Research Institute, 2-6-7 Kazusa Kamatari, Kisarazu 292-0818, Japan.
R&D Office, Aderans Co., Ltd., 1-26-6 Shinjuku, Shinjuku-ku, Tokyo 160-0022, Japan.
Biomolecules. 2025 Feb 28;15(3):353. doi: 10.3390/biom15030353.
Graves' disease (GD) is an autoimmune disorder that can be difficult to distinguish from other diseases due to symptom similarity. The exacerbation of GD owing to delayed diagnosis is a serious issue, and a novel accessible health screening system is needed. Therefore, this study investigated the association between GD and thyroid hormone levels in women's hair and evaluated the prediction accuracy of this non-invasive type of sample. By optimizing pretreatment and analysis techniques using liquid chromatography-mass spectrometry (LC-MS), free triiodothyronine (FT3) and thyroxine (FT4) could be detected in only 2 mg of hair with high sensitivity. Compared with healthy controls, the thyroid hormone levels in the hair of GD patients were significantly higher in correlation with blood levels. The predictive ability of hair thyroid hormones was analyzed using a receiver operating characteristic (ROC) curve, and the optimal cut-off value was determined via the Youden index. As a result, the area under the curve (AUC) was 0.974 (95% confidence interval (CI): 0.935-1.000) for FT3 and 0.900 (95% CI: 0.807-0.993) for FT4. The cut-off value was 0.133 pg/mg (sensitivity: 91.2%; specificity: 100%; positive predictive value (PPV): 100%; negative predictive value (NPV): 76.9%) for FT3 and 0.067 pg/mg (sensitivity: 70.6%; specificity: 100%; PPV: 100%; NPV: 50.0%) for FT4. Collectively, our new approach offers the possibility of accurately and non-invasively detecting GD using hair samples. Since hair can be stored and transported at room temperature, this system facilitates large-scale screening at locations including hair salons and homes, potentially enabling the early determination of GD outside of medical facilities.
格雷夫斯病（GD）是一种自身免疫性疾病，由于症状相似，可能难以与其他疾病区分开来。因诊断延迟导致的GD病情加重是一个严重问题，因此需要一种新型的便捷健康筛查系统。因此，本研究调查了女性头发中GD与甲状腺激素水平之间的关联，并评估了这种非侵入性样本的预测准确性。通过使用液相色谱-质谱联用（LC-MS）优化预处理和分析技术，仅2毫克头发就能以高灵敏度检测到游离三碘甲状腺原氨酸（FT3）和甲状腺素（FT4）。与健康对照相比，GD患者头发中的甲状腺激素水平与血液水平显著相关且更高。使用受试者工作特征（ROC）曲线分析头发甲状腺激素的预测能力，并通过约登指数确定最佳截断值。结果，FT3的曲线下面积（AUC）为0.974（95%置信区间（CI）：0.935 - 1.000），FT4的AUC为0.900（95%CI：0.807 - 0.993）。FT3的截断值为0.133 pg/mg（灵敏度：91.2%；特异性：100%；阳性预测值（PPV）：100%；阴性预测值（NPV）：76.9%），FT4的截断值为0.067 pg/mg（灵敏度：70.6%；特异性：100%；PPV：100%；NPV：50.0%）。总体而言，我们的新方法提供了使用头发样本准确、非侵入性检测GD的可能性。由于头发可以在室温下储存和运输，该系统便于在包括理发店和家庭在内的场所进行大规模筛查，有可能在医疗机构之外实现GD的早期诊断。
