Gene sequencing should be considered together with clinical lab results, including somatostatin suppression testing, before approaching a diagnosis of RTH.
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.
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.
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.
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.
Thyroid Hormone Resistance (RTH) is characterized by the diminished response of thyroid hormone-responsive tissues in varying degrees in association with elevated serum levels of total and free T4 and T3 and inappropriately normal or elevated TSH levels.
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.
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.
Thyroid hormone resistance was found to be expressed at the level of TRH gene regulation, due to lowered inhibition by mutant TRbeta1-T3 complexes and by their dominant negative effects on wild-type TRbeta1-T3 inhibition.
These data demonstrate that thyroid hormone resistance at the level of TRH gene regulation, due to reduced inhibitory actions of mutant TR-T3 complexes, as well as dominant negative effects upon WT hTR beta 1 mediated inhibition, likely contribute to elevated TSH values observed in the syndrome of thyroid hormone resistance.
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.
Mutational analysis of the MCT8 gene revealed mutations or deletions in the MCT8 gene in unrelated male patients with severe psychomotor retardation and biochemical findings consistent with thyroid hormone resistance.
In contrast, pseudohypoparathyroidism type Ib (PHP1B) is characterized mostly by resistance to PTH and often mild TSH resistance, usually without AHO features.
Finally, besides PTH deficiency, hypocalcemia can be due to PTH resistance in pseudohypoparathyroidism; when hormone resistance is generalized, patients can suffer from hypothyroidism due to TSH resistance.