Endocrine Abstracts

Disorders of thyroid hormone action are classified broadly, to encompass conditions with defective cellular uptake, metabolism or nuclear action of thyroid hormones. Mutations in SECISBP2 cause a multisystem disorder of defective selenoprotein synthesis, with features due to tissue-specific selenoprotein deficiencies (e.g. male infertility, muscular dystrophy), raised cellular reactive oxygen species due to lack of antioxidant selenoenzymes (e.g. photosensitivity, increased adipose mass and function), associated with a biochemical signature due to impaired conversion of T₄ to T₃ via selenium-containing deiodinases. Genomic thyroid hormone action is mediated via receptor subtypes (TRα, TRβ) with differing tissue distributions. TRβ-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, TRα1-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 TRα1 and β- mediated RTH exemplify the differing importance of receptor subtypes in tissues, providing a rational basis for receptor-specific drug development.

Generously supported by Clinical Endocrinology Trust