摘要
Background Resistance to thyroid hormone （RTH） is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor β（TRβ）. We report the clinical and laboratory characteristics and the genetic analysis of a patient with this rare disorder and his family members. Methods The clinical presentations and changes of thyroid function tests （TFTs） including magnetic resonance imaging （MRI） of pituitary and other laboratory tests were analysed. TFTs of his family＇s members were detected as well. Direct DNA sequencing of the TRβ gene was done for those with abnormal TFTs. Results The RTH child had goiter, irritability, aggressiveness, and sudoresis. His TFTs showed high levels of circulating free thyroid hormones （FT4 and FT3） and normal thyroid-stimulating hormone （TSH） concentrations. He felt worse when treated as hyperthyroidism （Grave disease） with thiamazole and his clinical presentations got improved obviously when treated as RTH with bromocriptine without obvious advert effect. We identified a novel missense mutation, A317D, located in exon 9 of the gene of this boy and his mother. His mother had not any clinical presentation, but having abnormal TFTs results. Conclusions This patient reported here was concordant with the criteria of RTH. The feature is dysfunction of hypothalamus-pituitary-thyroid axis. A novel mutation was found in the TRβ, A317D, of this family. This research verified the phenomena that there is a clinical heterogeneity within the same mutation of different RTH patients.
Background Resistance to thyroid hormone （RTH） is a dominant inherited syndrome of reduced tissue responsiveness to thyroid hormone. It is usually due to mutations located at the ligand-binding domain and adjacent hinge region of the thyroid hormone receptor β（TRβ）. We report the clinical and laboratory characteristics and the genetic analysis of a patient with this rare disorder and his family members. Methods The clinical presentations and changes of thyroid function tests （TFTs） including magnetic resonance imaging （MRI） of pituitary and other laboratory tests were analysed. TFTs of his family＇s members were detected as well. Direct DNA sequencing of the TRβ gene was done for those with abnormal TFTs. Results The RTH child had goiter, irritability, aggressiveness, and sudoresis. His TFTs showed high levels of circulating free thyroid hormones （FT4 and FT3） and normal thyroid-stimulating hormone （TSH） concentrations. He felt worse when treated as hyperthyroidism （Grave disease） with thiamazole and his clinical presentations got improved obviously when treated as RTH with bromocriptine without obvious advert effect. We identified a novel missense mutation, A317D, located in exon 9 of the gene of this boy and his mother. His mother had not any clinical presentation, but having abnormal TFTs results. Conclusions This patient reported here was concordant with the criteria of RTH. The feature is dysfunction of hypothalamus-pituitary-thyroid axis. A novel mutation was found in the TRβ, A317D, of this family. This research verified the phenomena that there is a clinical heterogeneity within the same mutation of different RTH patients.
