(A)–(C) Changes in markers of thyroid status over the course of the study (mean ± standard error). (D) Changes in treatment preference.

L-T3 has proven to be 4-5 times more biologically active and to take effect more quickly than L-thyroxine (L-T4).

Following this observation, the same group conducted a cross-sectional analysis to assess the association among 140 patients with EE and TH replacement hypothyroid treated with LT4. In this study population, REE did not differ significantly between patients achieving low-normal (TSH ≤ 2.5 μIU/mL) vs high normal TSH (TSH >2.5 μIU/mL). Conversely, free T3 level showed a direct correlation with EE, but also with indices of adiposity including body mass index (BMI), body composition, and fat free mass [49]. This latter observation is consistent with other cross-sectional studies that have clearly defined the positive association between circulating levels of T3 and adiposity [50, 51].

The authors demonstrated an inverse correlation between TSH and REE with a change of 15% for a TSH ranging from 0.1 to 10 μIU/mL. Of interest, free T4 remained within the normal range in all of the study volunteers. Nonetheless, the changes in REE with different LT4 doses were demonstrated in every patient [46].

There was a boy who was born with congenital hypothyroidism and was raised on traditional T3 (Cytomel). He was never treated with a T4-containing medicine, and so essentially never had a molecule of T4 in his body. By age 26 he had developed normally with no problems.