Endocrine Abstracts

Disorders of thyroid hormone action are classified broadly, to encompass conditions with defective cellular uptake, metabolism or nuclear action of thyroid hormones. We describe recent insights into two rare disorders of thyroid hormone action. Impaired conversion of T₄ to T₃ enables recognition of a multisystem disorder due to mutations in SECISBP2 – a factor directing synthesis of 25 different human, selenocysteine-containing proteins that include deiodinase enzymes. We have discovered that progressive, aneurysmal, aortic dilatation is a life-threatening manifestation of this disorder. Cystic medial degeneration of the aorta, similar to that seen in other aortopathy syndromes (e.g. Marfan’s, Loeys-Dietz), is associated with raised reactive oxygen species, oxidative damage and apoptosis in patient-derived aortic smooth muscle cells. Secisbp2 knockdown in zebrafish or vessel wall selenoprotein depletion in mice, recapitulate the human phenotype. How selenoprotein deficiency mediates vascular degeneration and whether antioxidants can inhibit this process, remains to be elucidated.