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

P>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 >= 0 center dot 5 < 1 center dot 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 center dot 48 +/- 0 center dot 77 vs. 1 center dot 21 +/- 0 center dot 62 mU/l, P = 0 center dot 293) at average daily doses of 40 center dot 3 +/- 11 center dot 3 mcg L-T3 and 115 center dot 2 +/- 38 center dot 5 mcg L-T4, L-T3: L-T4 ratio 0 center dot 36 +/- 0 center dot 06. TRH stimulation test resulted in similar L-T3 vs. L-T4 TSH responses with AUC(0-60) of 326 center dot 1 (95% CI 232 center dot 6-457 center dot 1) and 247 center dot 1 (95% CI 153 center dot 8-397 center dot 1) mU* min/l (P = 0 center dot 285); and C-max of 6 center dot 83 (95% CI 4 center dot 88-9 center dot 55) and 5 center dot 23 (95% CI 3 center dot 31-8 center dot 3) mU/l (P = 0 center dot 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.