Resistance to Thyroid Hormone and Cardiovascular Risk

Abstract

Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of impaired tissue responsiveness to thyroid hormones (TH) characterized by high circulating TH in the presence of unsuppressed thyroid-stimulating hormone (TSH). TH achieve their action on the heart chiefly via thyroid hormone receptor alpha 1 (TR〈1), which is the TH receptor (TR) isoform predominantly expressed in such an organ. Data derived from animal models suggest that in RTH the overstimulation of the TR〈1 pathway by the high TH levels could explain the cardiovascular abnormalities seen in these animals, although the discordant cardiac gene expression profile between wild-type (wt) and transgenic mice treated with triiodothyronine (T3) imply that the effects of RTH on the heart are complex and not completely explicable by the heightened T3/TR〈1 signaling. To date, only a few studies have evaluated cardiovascular risk in RTH, with conflicting results, confirming the large variability of the RTH phenotype. In particular, some reports show that several cardiovascular parameters seem to move toward hyperthyroidism, while others show a pattern that resembles thyroid hormone deficiency. Finally, recent data suggest that in addition to reduced vascular compliance and echocardiographic abnormalities, RTH subjects may exhibit some features of metabolic syndrome, suggesting an overall increased cardiometabolic risk in this disorder.