Resistance to thyroid hormone α, revelation of basic study to clinical consequences

In the past 3 years, 15 patients with resistance to thyroid hormone alpha (RTH alpha), nine THRA gene mutations have been reported, reforming classification of RTH. RTH alpha exhibits distinguished clinical manifestations from RTH beta, including growth retardation, skeletal dysplasia, impaired neurodevelopment, cardiovascular dysfunction, constipation and specific thyroid axis type. This review focuses on possible pathogenesis by revelatory basic science of RTHa animal models in vivo, and patients' mutant thyroid hormone receptor alpha (TR alpha) in vitro. Clinical manifestations and L-T4 effects are summarized, showing strong correlation to the severity of mutation mostly within the domain which dominated TR interaction with T3 and its corepressors/coactivators. In particular, we propose the diagnosis clues and promising treatment for clinicians.