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

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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.