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)].
Furthermore, when several clinical parameters of THR were compared in several affected members from two kindreds with GRTH, we found that two cases in one kindred exhibited a high mutant-to-normal hTR beta ratio and had considerably more bone resistance during their development.
Conclusions Fluctuating thyroid function tests in addition to thyroid peroxidase antibody (TPO Ab) positivity complicated the diagnosis of RTH, initially diagnosed as Hashimoto's thyroiditis.
Resistance to thyrotropin (TSH) (RTSH; defined by elevated TSH and a normal or hypoplastic thyroid gland) can be caused by mutations in genes encoding the TSH receptor and PAX8, and it has been linked to a locus on chromosome 15.
His normal α-subunit and sex hormone binding globulin, partially suppressed TSH by high dose triiodothyronine (T3), and positive TSH response to thyrotropin-releasing hormone stimulation were consistent with resistance to thyroid hormone syndrome.
These data suggest an iodide organification defect in 17 cases; an iodide transport defect (NIS defect) in three, probable TSH resistance in 10, and a TG synthesis defect in two cases.
The present study suggests that therapies aimed at the TR-NCOR1 interaction or its downstream actions could be tested as potential targets in treating RTH.
It has been reported that serum of patients with RTHlacks autoantibodies against thyroglobulin (Tg) and thyroid peroxidase (TPO), except in rare cases where there is co-occurrence of coincidental autoimmune thyroiditis.
It has been reported that serum of patients with RTHlacks autoantibodies against thyroglobulin (Tg) and thyroid peroxidase (TPO), except in rare cases where there is co-occurrence of coincidental autoimmune thyroiditis.
The shared clinical picture caused by these defects is a variable degree of thyrotropin resistance (RTSH [MIM 275200]), accompanied in its severe form by thyroid gland hypoplasia.
To determine the mechanism of RTH caused by these mutants, the interaction of wild type (wt) and mutant TRs with the corepressor, NCoR, and the coactivator, SRC-1, was tested in gel-shift assays.
Periodically hyperthyroid phenotype in thyroid hormone resistance is associated with mutation D322N in the thyroid hormone receptor beta gene: transcriptional properties of the mutant and the role of retinoid X receptor.
This study was undertaken to test the usefulness of SHBG determinations to define the thyroid status in two hyperthyroxinemic states: thyroid hormone resistance (THR) and familial dysalbuminemic hyperthyroxinemia (FDH).
In vitro effects of the mutations on cAMP production and TSH binding were investigated in COS7 cells. cAMP production was evaluated by transfecting a cAMP response element (CRE)-luciferase reporter with pSVL-TSHR and pSVK3-GNAS vectors.
A genetic and functional GNAS study was undertaken in a boy with morbid obesity (body mass index Z-score of 5 at the age of 3 yr, with a body fat fraction of 40%, which is more than twice normal), TSH resistance, pseudohypoparathyroidism, and a prothrombotic state.
Candidate genes were then evaluated for their possible involvement in the RTH phenotype in these 4 families: 2 coactivators [NCoA-1 (SRC-1) and NCoA-3 (AIB-1)], 2 corepressors (NCoR and SMRT), and a coregulator (RXRgamma).
To determine the mechanism of RTH caused by these mutants, the interaction of wild type (wt) and mutant TRs with the corepressor, NCoR, and the coactivator, SRC-1, was tested in gel-shift assays.
Therefore, genetic testing of the candidate genes THRB and SLC16A2 should be performed for diagnosis of RTH and AHDS in patients with the suggestive clinical phenotype.
In particular, the application of 3,3',5-triiodothyroacetic acid (Triac) in RTH due to defective TRβ and the role of 3,5-diiodothyropropionic acid (DITPA), 3,3',5,5'-tetraiodothyroacetic acid (Tetrac) and Triac in MCT8 deficiency will be highlighted.