Resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) or thyroid hormone action defect (THAD) is the most frequent form of syndromes of reduced sensitivity to thyroid hormone. It is characterized by variable tissue hyposensitivity to thyroid hormone. RTHβ (formerly only RTH) is caused by mutations in the thyroid hormone receptor β gene (THRB). The clinical phenotype reflects the dysbalance between resistance of tissues predominantly expressing the thyroid hormone receptor β-isoforms 1 and 2 and the overstimulation of tissues mainly expressing the thyroid hormone receptor α-isoform to thyroid hormones. The hallmark of RTHβ is goiter, sinus tachycardia, attention deficit hyperactivity disorder in the context of increased levels of triiodothyronine/free thyroxine and nonsuppressed thyroid-stimulating hormone. Only recently have mutations in the thyroid hormone receptor α gene (THRA) been identified causing a new form of RTH, RTHα. The few patients described so far suffered from mental retardation of variable degree, short stature with decreased subischial leg length, chronic constipation and bradycardia. This review provides an overview of clinical, biochemical and genetic aspects of RTHα and RTHβ relevant for diagnosis, treatment and counseling of affected patients and families.