Disorders of thyroid hormone action: diagnosis, pathophysiology and therapy

We will study disorders that are characterised by defects in genes that control the entry of thyroid hormones into cells, their conversion to the active hormone and action via two types of receptor. Defective hormone entry causes failure of brain development.

Defects in SECISBP2 causes deficiency of selenium-containing proteins which leads to multisystem disease with impaired thyroid hormone conversion and degeneration of the aorta. We will find out how aortic degeneration occurs using selenoprotein-deficient aortic cells from mice and patients and we will test whether antioxidants can prevent this process. Defects in thyroid receptor α, cause a disorder with features of thyroid underactivity although blood thyroid hormone levels remain near normal. We will find out its genetic basis and features and develop a diagnostic test that will enable us to identify patients who may benefit from thyroid hormone treatment. We will trial whether treatment with a thyroid hormone-like drug can be used to treat this disorder.

Our findings will add to our knowledge about the pathophysiology of disorders of thyroid hormone action and form the basis for improved diagnostics and therapy.