Endocrine Abstracts

Resistance to Thyroid hormone (RTH) encompasses various disorders of Thyroid Hormone (TH) Action, including defective signalling through TH Receptors (RTH alpha, RTH Beta), abnormal TH metabolism (Selenoprotein deficiency) and altered cellular entry of TH (MCT8 defects). In this talk, I will focus on RTH alpha and beta. RTH beta is usually associated with mutations in the THRB gene and is often readily identified, due to the associated typical biochemical pattern of raised TH levels and non-suppressed TSH. Resistance to the action of TH occurs in tissues expressing the beta form of the TH receptor (hypothalamus, pituitary, liver), but TR alpha expressing tissues are exposed to elevated TH levels. Patients with Resistance to Thyroid Hormone alpha (RTH alpha; due to mutations in the THRA gene) are highly challenging to identify because many patients only have mildly abnormal (or even normal) thyroid hormone levels. Resistance to the action of TH occurs in tissues expressing the alpha form of the TH receptor (bone, skeletal muscle, brain and heart). The clinical features/phenotype of both RTHalpha and RTHbeta are highly variable; from mild developmental delay to severe learning impairment and disability in RTHalpha, and asymptomatic states to significant tissue specific thyrotoxicosis in RTHbeta. Treatment for RTHbeta is not always required, but beta-blockade and tri-iodothyroacetic acid (TRIAC) can be considered. Many patients with RTHalpha respond to thyroxine therapy, but optimal dosing schedules and treatment targets are not known.