Resistance to thyroid hormone (RTH) is usually dominantly inherited and is 
characterized by elevated free thyroid hormones in the serum and failure to 
suppress pituitary thyroid stimulating hormone (TSH) secretion with variable 
refractoriness to hormone action in peripheral tissues. Two major forms of the 
disorder are recognized: asymptomatic individuals with generalized resistance 
(GRTH) and patients with thyrotoxic features, suggesting predominant pituitary 
resistance (PRTH). Molecular genetic analyses indicate that both GRTH and PRTH 
are associated with diverse mutations in the thyroid hormone receptor beta gene, 
which localize to three regions in the hormone binding domain of the receptor. 
In addition to being functionally impaired, the mutant receptors are also able 
to inhibit their wild-type counterparts in a dominant negative manner. 
Recognized features of RTH include failure to thrive, growth retardation and 
attention-deficit hyperactivity disorder in childhood, and goitre and thyrotoxic 
cardiac symptoms in adults. The pathogenesis of variable tissue resistance is 
not fully understood but may be related to the differing tissue distributions of 
a and b thyroid hormone receptors and variable dominant negative activity of 
mutant receptors on different target genes.