The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized, double blind, cross-over study in thyroidectomized patients

Abstract

Context: The substitution of liothyronine (L-T3) for levothyroxine (L-T4) is commonly employed during thyroid hormone (TH) withdrawal in preparation for diagnostic and therapeutic interventions on thyroid cancer patients. Presently, only limited data are available on the L-T3 for L-T4 therapeutic substitution. Objective To characterize the pharmcodynamic equivalence of L-T3 and L-T4.

Design: Randomized, double-blind, cross-over intervention study.

Setting: NIH clinical center.

Patients: Ten thyroidectomized patients.

Interventions: Study participants were treated with L-T3 or L-T4 with a target TSH >or= 0.5 <or= 1.5 mU/l for at least 30 days before undergoing inpatient testing. Following testing, subjects crossed-over according to the same scheme.

Main outcome measures: Area under the serum concentration-time curve of TSH from 0 to 60 min (AUC(0-60)) and peak TSH serum concentration (C(max)) following thyrotropin-releasing hormone (TRH) stimulation test, total L-T4 and L-T3 dose (mcg/kg), and L-T4/L-T3 ratio.

Results: No difference was observed for time 0 TSH values between L-T3 and L-T4 replacement phases (1.48 +/- 0.77 vs. 1.21 +/- 0.62 mU/l, P = 0.293) at average daily doses of 40.3 +/- 11.3 mcg L-T3 and 115.2 +/- 38.5 mcg L-T4, L-T3: L-T4 ratio 0.36 +/- 0.06. TRH stimulation test resulted in similar L-T3 vs. L-T4 TSH responses with AUC(0-60) of 326.1 (95% CI 232.6-457.1) and 247.1 (95% CI 153.8-397.1) mU* min/l (P = 0.285); and C(max) of 6.83 (95% CI 4.88-9.55) and 5.23 (95% CI 3.31-8.3) mU/l (P = 0.383).

Conclusions: This is the first study addressing the equivalency between L-T3 and L-T4 therapy measured by baseline and TRH-stimulated TSH. The therapeutic substitution of L-T3 for L-T4 was achieved at approximately 1:3 ratio.

Trial registration: ClinicalTrials.gov NCT00106119.

Figures

Figure 1

CONSORT flow-chart: research protocol recruiting, screening, drop out, and completion rate.

Figure 2

Equivalency for thyroid hormone replacement therapy. A: individual l-T3 l-T4 equivalency at steady state. B: box-plot indicating median and distribution of the daily doses of l-T3 and l-T4 replacement therapy. Data are expressed as mcg/kg daily dose on a thrice daily administration scheme.

Figure 2

Equivalency for thyroid hormone replacement therapy. A: individual l-T3 l-T4 equivalency at steady state. B: box-plot indicating median and distribution of the daily doses of l-T3 and l-T4 replacement therapy. Data are expressed as mcg/kg daily dose on a thrice daily administration scheme.

Figure 3

24-hour profile of total T3 levels (panel A) and TSH (panel B) on ◆ lT-3 and (●) l-T4 thyroid hormone replacement therapy. Samples were obtained at 4-hour intervals, except for the second TSH time-point where the time 0 TRH stimulation test (08:00) was substituted for the 10:00 time-point to avoid the artifact of the TRH-stimulated rise in TSH.

Figure 3

24-hour profile of total T3 levels (panel A) and TSH (panel B) on ◆ lT-3 and (●) l-T4 thyroid hormone replacement therapy. Samples were obtained at 4-hour intervals, except for the second TSH time-point where the time 0 TRH stimulation test (08:00) was substituted for the 10:00 time-point to avoid the artifact of the TRH-stimulated rise in TSH.

Figure 4

Results of the TRH stimulation test. Study volunteers (n=8) received a 200 mcg intravenous injection of TRH while on ◆ lT-3 and ● l-T4 thyroid hormone replacement therapy at 08:00. Time 0 indicates the average of times -15 and 0 min. Data expressed as geometric means and associated 95% confidence limits.