Selection and analysis of cases with atypical responses in the pituitary-thyroid axis from a large thyroid database.

TSH和游离T4指数（FT 41）之间的关系进行了分析，从一个大型的实验室数据库，以选择病例显示垂体甲状腺轴的非典型反应，其特点是高TSH，尽管高FT 41。从7700例资料中，筛选出67例TSH分泌异常者，分析其临床特点及激素水平的系列变化。其中27例为持续替代治疗的克汀病患儿。另外4例为因甲状腺癌行甲状腺全切除术的患者。尽管进行了充分的替代治疗，TSH水平仍然很高。在两组患者中，TSH水平均随FT_（41）的变化而反向波动，提示存在完整的负反馈机制，但设定值偏置。在另一系列研究中，TSH与游离T_4（FT_4）的关系也发现了相同的患者组。发现3例桥本甲状腺炎患者，他们没有明显的原因导致TSH分泌不当。对这些病例进行了生化分析，包括凝胶色谱法，对连续稀释的样品进行免疫反应性试验，寻找抗TSH或T4的自身抗体。近年来，TSH分子糖基化模式的改变导致其生物活性的改变的报道较多。因此，需要进一步的研究来确定我们病例中糖基化模式的这种变化。无论如何，我们寻找非典型病例的方法是如此有效，它将有助于发现涉及垂体-甲状腺轴的新疾病。

The relation between TSH and free T4 index (FT41) was analyzed from a large laboratory database in order to select cases showing atypical responses in the pituitary thyroid axis, characterized by high TSH despite high FT41. From among 7700 data, 67 cases with such inappropriate secretion of TSH were singled out and their clinical features and serial changes in the hormone levels were examined. Twenty-seven cases among them were children with cretinism under constant replacement therapy. Another four cases were those who underwent total thyroidectomy for thyroid cancer. The level of TSH remained high despite sufficient replacement therapy. In both groups of patients, the level of TSH, however, fluctuated inversely with variations of FT41 in response to the changing replacement dosage, thus, suggesting the presense of intact negative-feedback mechanism but with a skewed set point.In another serie of study, the relation between TSH and free T4 (FT4) were examined and identical groups of patients were found. In addition, three patients with Hashimoto's thyroiditis were found, who had no apparent reasons for the inappropriate secretion of TSH. Biochemical analyses of those cases were carried out, inclusing gel chromatography, a test for immunoreactivity for serially diluted samples, a search for autoantibodies against TSH or T4. None of them were positive.Recently, there have been many reports of changes in glycation patterns of TSH molecule resulting in altered bioactivity. Therefore, further study is required to identifiy such a change in the glycation pattern in our cases. Anyway, our approach to search for atypical cases is so efficient that it will facilitate discoveries of novel disorders involving the pituitary-thyroid axis.