Disorders of thyroid hormone action are classified broadly, to encompass conditions with defective cellular uptake, metabolism or nuclear action of thyroid hormones. Genomic thyroid hormone action is mediated via receptor subtypes (TRalpha, TRbeta) with differing tissue distributions. TRbeta-mediated Resistance to Thyroid Hormone (RTH) is characterised by elevated thyroid hormones, raised metabolic rate and cardiac hyperthyroidism but hepatic resistance (dyslipidaemia, steatosis). In contrast, TRalpha1-mediated RTH patients exhibit growth retardation, skeletal dysplasia and constipation together with reduced metabolic rate and cardiac hypothyroidism, with near-normal thyroid hormone levels. The contrasting phenotypes of TRalpha1 and beta- mediated RTH exemplify the differing importance of receptor subtypes in tissues, providing a rational basis for receptor-specific drug development. Mutations in SECISBP2 and TRU-TCA1-1 cause a multisystem disorder of defective selenoprotein synthesis, with features attributable both to tissue-specific selenoprotein deficiencies (e.g. male infertility, muscular dystrophy) and raised cellular reactive oxygen species due to lack of antioxidant selenoenzymes (e.g. photosensitivity, increased adipose mass and function). Additionally, patients have a characteristic biochemical signature resulting from impaired conversion of T4 to T3 via selenium-containing deiodinases. This presentation will describe clinical features of these conditions, which increase our understanding of thyroid hormone action and inform potential future therapeutic developments.
20 - 23 May 2017
European Society of Endocrinology