The thyroid gland produces two primary hormones: thyroxine (T4) and triiodothyronine (T3). T4 is considered a prohormone and must be converted in peripheral tissues to the more biologically active T3. Most patients treated for hypothyroidism receive T4-only therapy, which relies on this conversion process. Some thyroid preparations, however, contain both T4 and T3.
A study published in the New England Journal of Medicine (1999; 340(6):424–429) compared the effects of thyroxine (T4) alone with a combination of thyroxine and triiodothyronine (T3) in 33 patients with hypothyroidism. Each participant completed two five-week treatment periods in a crossover design. During one phase, patients received their usual dose of T4 alone. During the other phase, 50 micrograms of T4 were replaced with 12.5 micrograms of T3, while the remainder of the T4 dose was maintained.
Participants underwent standardized testing of cognitive performance as well as mood and physical well-being assessments. In 6 of 17 cognitive tests, patients performed better—or closer to normal—during the combination T4/T3 treatment than during T4-only therapy. Similarly, on 10 of 15 visual-analogue scales evaluating mood and physical symptoms, scores were significantly improved during the combination therapy phase.
The authors concluded that partial substitution of T3 for T4 may improve neuropsychological function and mood in some patients with hypothyroidism. While the study was relatively small and short in duration, it raised important questions about whether T4-only therapy is optimal for all patients, particularly those who continue to experience symptoms despite having “normal” laboratory values.
