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Context  The pharmacokinetics of liothyronine causes concerns for cardiovascular toxicity. While the effects of sustained increase in serum T3 concentrations are well described, little is known on the effects of acute changes in T3 concentrations due to rapid action of thyroid hormone.    Objective  To assess the clinical relevance of transient increase of T3 levels on cardiovascular system and energy metabolism.    Setting  Double-blind, three arms, placebo controlled, cross-over study (ClinicalTrials.gov Identifier: NCT03098433).    Study Participants  Twelve volunteers (3 females, 9 males), age 27.7 ± 5.1 years.    Intervention  Oral administration of liothyronine 0.7 mcg/kg, equimolar dose of levothyroxine (0.86 mcg/kg), or placebo in three identical study visits. Blood samples for total T3, free T4 were collected at times 0’, 60’ 120’ 180’ 240’. Continuous recording of heart rate, blood pressure, and hemodynamic data was performed using the volume clamp method. Resting energy expenditure was measured by indirect calorimetry. An echocardiogram was performed on each study visit at baseline and after the last blood sampling.    Main Outcome Measures  Changes in cardiovascular function and energy expenditure.    Results  Following the administration of liothyronine, serum T3 reached a C max  of 421 ± 57 ng/dL with an estimated T max  of 120 ± 26 minutes. No differences between study arms were observed in heart rate, blood pressure, hemodynamics parameters, energy expenditure, and in echocardiogram parameters.    Conclusions  The absence of measurable rapid effects on the cardiovascular system following a high dose of liothyronine supports the rationale to perform long-term studies to assess its safety and effectiveness in patients affected by hypothyroidism.

Acute Effects of Liothyronine Administration on Cardiovascular System and Energy Metabolism in Healthy Volunteers