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 ≥ 0·5 ≤ 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.