The thyroid hormones Thyroxine (T4) and Triiodothyronine (T3) can be measured directly in serum by radioimmunoassay. Most serum T4 and T3 circulates bound to specific serum-binding proteins but the small unbound fraction, free T4, correlates best with hormonal activity. The free T4 concentration can be measured directly and also can be estimated from the T3-resin uptake as the free T4 index (FT4-I). In hypothyroidism, T4 and FT4-I are decreased and when the disorder results from thyroid gland failure, serum TSH will be elevated as well. Indeed, an increase in serum TSH is the most sensitive index of thyroid gland failure. Hyperthyroidism is associated with increased serum T4, T3, and free T4. About 5% of patients have a selective increase in T3 secretion: T3 thyrotoxicosis. In these, serum T4 is normal but serum T3 is elevated. An absent TSH response to thyrotropin-releasing hormone (TRH) is the hallmark of hyperthyroidism due to suppression of anterior pituitary TSH secretion.