l-Thyroxine in an Oral Liquid or Softgel Formulation Ensures More Normal Serum Levels of Free T4 in Patients with Central Hypothyroidism

CONTEXT: l-Thyroxine (l-T4) therapy of central hypothyroidism (CH) is guided by measurements of serum free thyroxine (FT4), which should be above the midnormal range value (MNRV). In some countries, novel formulations of oral l-T4 (liquid or softgel) are available further to the classic tablets. The intestinal absorption of either novel formulation is greater than tablets in patients with primary hypothyroidism. OBJECTIVE: To evaluate whether new oral formulations of l-T4 could be considered optimal in patients with CH who do not reach the FT4 target using tablet l-T4. DESIGN: Our observation of six patients with isolated CH and serum FT4 below MNRV under stable adequate doses of tablet l-T4 (median 1.51 μg/kg bw/day), prompted us to switch them to liquid (n = 4) or softgel (n = 3) l-T4 at the same dose, and verify whether FT4 increased above MNRV. A seventh patient with FT4 above MNRV was enrolled because she wanted a “more modern formulation.” Postswitch FT4 was measured at least twice with the same kit as preswitch FT4. RESULTS: In the first six patients, postswitch FT4 averaged 13.0 ± 1.6 pg/ml compared to 10.4 ± 1.8 preswitch FT4 (P = 0.00026), with 11/13 (85%) measurements above MNRV compared to 0/20. In the liquid or softgel l-T4 group, postswitch FT4 averaged 13.1 ± 1.6 vs. 10.6 ± 0.9 pg/ml preswitch (P = 0.0004) or 12.9 ± 2.1 vs. 10.3 ± 2.4 (P = 0.048), respectively. In the seventh patient (switched to liquid l-T4), averages were 18.3 vs. 15.2 pg/ml, and proportions 4/4 vs. 2/2. CONCLUSION: In CH patients, oral liquid or softgel l-T4 administered at the same doses as tablet l-T4 ensures target serum FT4 levels above MNRV that tablet l-T4 may miss. In turn, this performance suggests the more favorable pharmacokinetics profile of either novel formulation compared with the tablet formulation.