ESPE Abstracts

The standard of care for the treatment of hypothyroidism is the administration of daily tablets of levothyroxine (LT4) at doses that normalize serum TSH levels. In most patients, this approach elevates serum thyroid hormone (TH) levels and eliminates symptoms of overt hypothyroidism. Nonetheless, treatment with LT4 in adults does not fully normalize the TH economy. Despite normal TSH levels, many patients exhibit a reduction in the serum T3/T4 ratio due to a relative excess of T4 and a relative deficiency of T3; in approximately 15% of the patients, serum T3 is below the normal reference range. New studies have shown that these residual abnormalities in TH homeostasis are due to an unbalance in T4 to T3 deiodination between the hypothalamus/pituitary gland and the other tissues involved in extrathyroidal T3 production. This could be clinically relevant as lower T3 levels could explain the residual hypercholesterolemia, increased utilization of statins, subnormal energy expenditure, and difficulty managing body weight frequently observed in LT4-treated patients. In addition, many adult patients prefer combination therapy with T4+T3; this is also observed in randomized clinical trials. In fact, the number of patients started in combination therapy, synthetic LT4+LT3 or desiccated thyroid extract (DTE) has doubled in the last 10 years. In LT4-treated children with congenital hypothyroidism, the serum T3/T4 ratio was found to be lower, but the utilization of therapy with LT4+LT3 has been limited to cases of consumptive hypothyroidism. Further studies in children with hypothyroidism could explore whether monotherapy with LT4 restores TH signaling in all forms of hypothyroidism.