Clinical characteristics of thyroid hormone resistance syndrome in two cases with different subtypes / 中华儿科杂志

ABSTRACT

Objective@#To analyze the clinical characteristics of children with two types of thyroid hormone resistance (RTH) syndrome, and to detect the variants of thyroid hormone receptor alpha(TRα) and TRβ gene in children.@*Method@#Two children with RTH were reported in regard to clinical manifestation, laboratory examination and genetic variants. Some related reports in literature were reviewed.@*Result@#Case 1 was a girl, 10 years old, with thyroid enlargement for several days and without thyrotoxicosis. Laboratory work-up revealed that free thyroxine (FT4) was 65.77 pmol/L (reference 12-22) , free triiodothyronine (FT3) was 15.36 pmol/L (reference 3.1-6.8) and thyroid stimulating hormone (TSH) level was normal. There was a likely pathogenic missense variant detected in TRβ gene and this patient was diagnosed with RTHβ. Case 2 was a boy, 3 years old, with classic features of hypothyroidism(growth retardation, developmental retardation, skeletal dysplasia) but had only borderline-abnormal thyroid hormone levels. Targeted sequencing showed a de novo heterozygous nonsense variant in TRα gene which is a pathogenic variant and this patient been diagnosed with RTHα.@*Conclusion@#Thyroid enlargement is a common clinical manifestation of RTHβ, with laboratory work-up reveals elevated FT4 and FT3 levels but TSH level is normal. The clinical manifestations of RTHα are similar to those of hypothyroidism, but the thyroid hormone levels are almost normal. The gene sequence and the pathogenicity analysis for TRα and TRβ will help to make a definitive diagnosis.