Maternal Resistance to Thyroid Hormone β and Pregnancy Outcomes
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Resistance to thyroid hormone (RTH), a dominantly-inherited disorder, typically due to heterozygous mutations (over 230 different mutations described hitherto) in the thyroid hormone receptor (TR) which mediates negative feedback by thyroid hormones (TH) within the hypothalamo pituitary-thyroid axis, is characterised by raised circulating TH (free T4 and free T3) and non suppressed TSH. The clinical phenotype of RTH is variable, encompassing both hyperthyroid (e.g. failure to thrive in infancy; anxiety, tachycardia, low body weight in adults) and hypothyroid (e.g.dyslipidemia, steatosis) features, attributable to the actions of elevated TH on either hormone sensitive, TR-expressing tissues or hormone-resistant, TR-expressing organs respectively (1). Knowledge that conventional maternal hyperthyroidism (e.g. due to Graves’ disease) has deleterious consequences in pregnancy prompts consideration of what the outcomes of pregnancies in which a hyperthyroxinemic mother with RTH carries a fetus of either concordant (TR mutant), or discordant (wild type or normal TR) genotype, might be.
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1945-7197