Abstract
ContextThe 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.ObjectiveTo assess the clinical relevance of transient increase of T3 levels on cardiovascular system and energy metabolism.SettingDouble-blind, three arms, placebo controlled, cross-over study (ClinicalTrials.gov Identifier: NCT03098433).Study ParticipantsTwelve volunteers (3 females, 9 males), age 27.7 ± 5.1 years.InterventionOral 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 MeasuresChanges in cardiovascular function and energy expenditure.ResultsFollowing the administration of liothyronine, serum T3 reached a Cmax of 421 ± 57 ng/dL with an estimated Tmax of 120 ± 26 minutes. No differences between study arms were observed in heart rate, blood pressure, hemodynamics parameters, energy expenditure, and in echocardiogram parameters.ConclusionsThe 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.
Highlights
The goals of the treatment of hypothyroidism are “to achieve a state of euthyroidism and normalization of the circulating levels of TSH and thyroid hormones” [1], whereby TSH is used as a powerful and reliable proxy for euthyroidism owing to its robust correlation with free T4 concentration [2]
The accrual occurred between July, 2017 and June 2019, and twelve volunteers (3 females, 9 males, age 27.7 ± 5.1 years, weight 75.0 ± 12.9 Kg) completed the study
No adverse event was reported, and study volunteers did not report any subjective difference in well-being, anxiety, thermoregulation, or heart rate among the three interventions
Summary
The goals of the treatment of hypothyroidism are “to achieve a state of euthyroidism and normalization of the circulating levels of TSH and thyroid hormones” [1], whereby TSH is used as a powerful and reliable proxy for euthyroidism owing to its robust correlation with free T4 concentration [2] This is commonly achieved with levothyroxine (LT4) which is relatively inexpensive, available in multiple strengths and administered in single dose. A significant percentage of patients adequately treated with LT4 complain of residual symptoms which may be attributed to hypothyroidism [7] These observations have prompted interest in LT4/Liothyronine (synthetic T3, LT3) combination therapy or desiccated thyroid extracts as means to correct for the loss of endogenous T3, and improve symptomatology [8]
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