Abstract
BACKGROUND: Thyroid hormones influence the function of essentially every system of the body, including the cardiovascular and metabolic system. Thyroid hormone replacement with levothyroxine (LT4) is the mainstay of pharmacological management for people with (especially clinically overt) hypothyroidism, and it is important to ensure the cardiovascular and metabolic safety of this treatment. This is especially so as in hypothyroidism, cardiometabolic risk factors and cardiovascular disease are highly prevalent conditions and will often coexist in an individual patient. Accordingly, we have reviewed the cardiometabolic consequences of hypothyroidism and intervention with thyroid hormone replacement. MAIN BODY: Numerous observational studies and meta-analyses have described multiple potentially adverse cardiometabolic consequences of hypothyroidism, including exacerbation of cardiovascular and metabolic risk factors (especially dyslipidaemia), functional impairment of the heart and vasculature (including accelerated atherosclerosis) and increased risk of advanced cardiovascular outcomes. LT4 usually improves cardiometabolic risk factors in people with hypothyroidism and some (but not all) studies have reported improved vascular and cardiac function in LT4-treated populations. Observational data have suggested the possibility of improved cardiometabolic outcomes with LT4 treatment, particularly in younger people with hypothyroidism, although data from randomised, controlled trials are needed here. Importantly, LT4 (with or without additional triiodothyronine) appears to be safe from a cardiovascular perspective, as long as overtreatment and iatrogenic thyrotoxicosis are avoided. CONCLUSIONS: Overall, the current evidence base supports intervention with LT4 to protect the cardiometabolic health of people with hypothyroidism who require thyroid hormone replacement, although more data on long-term clinical outcomes are needed.