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- W2003446532 abstract "Resistance to thyroid hormone (RTH) is a rare genetic disorder associated with diverse mutations in the thyroid hormone receptor beta-gene. TSH-dependent thyroid hyperstimulation, leading to goiter and elevated thyroid hormone levels, is a characteristic feature of RTH. However, about 60% of untreated resistance patients have circulating TSH levels within the normal range, raising the possibility that the biological activity of TSH is altered. We, therefore, assayed the bioactivity of circulating TSH in 11 patients from 8 different kindreds with RTH, measuring cAMP production in Chinese hamster ovary cells transfected with the recombinant human TSH receptor as well as in FRTL-5 cells. The ratio of biologically active vs. immunoreactive TSH (B/I) was significantly higher in RTH patients than in 8 normal controls [TSH B/I, 4.2 +/- 0.9 (range, 2.2-11.9) vs. 1.3 +/- 0.2 (range, 0.6-2.1)]. TSH released in response to TRH had a bioactivity similar to that of circulating TSH under basal conditions. On the contrary, supraphysiological doses of T3 normalized the B/I ratio of circulating TSH. Concanavalin-A chromatography of TSH from RTH patients showed the presence of circulating forms with altered carbohydrate branching. Our data indicate that the bioactivity of circulating TSH in thyroid hormone resistance syndromes is enhanced and can be normalized after T3 administration. These findings may account for the occurrence of goiter and elevated thyroid hormone levels in RTH patients despite normal serum TSH concentrations." @default.
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- W2003446532 date "1994-05-01" @default.
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- W2003446532 title "Evidence for the secretion of thyrotropin with enhanced bioactivity in syndromes of thyroid hormone resistance." @default.
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- W2003446532 doi "https://doi.org/10.1210/jcem.78.5.8175956" @default.
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