AUTHOR=Phan Giao Q. , Yavuz Sahzene , Stamatouli Angeliki M. , Madan Ritu , Chen Shanshan , Grover Amelia C. , Nilubol Naris , Bedoya Pablo , Trankle Cory , Markley Roshanak , Abbate Antonio , Celi Francesco S. 

TITLE=A feasibility double-blind trial of levothyroxine vs. levothyroxine-liothyronine in postsurgical hypothyroidism

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1522753

DOI=10.3389/fendo.2025.1522753

ISSN=1664-2392

ABSTRACT=ContextDespite normalization of Thyrotropin (TSH), some patients with hypothyroidism treated with Levothyroxine (LT4) report residual symptoms which may be attributable to loss of endogenous triiodothyronine (T3).ObjectiveFeasibility trial LT4/liothyronine (LT3) combination vs. LT4/placebo in post-surgical hypothyroidism.DesignDouble-blind, placebo-controlled, 24-week study.SettingAcademic medical centerPatientsIndividuals with indications for total thyroidectomy and replacement therapy.InterventionsLT4/LT3 5 mcg (twice daily) vs. LT4/placebo (twice daily). LT4 was adjusted at 6- and 12-weeks with the goal of baseline TSH ± 0.5 mcIU/ml.Main Outcome MeasuresChanges in body weight, cholesterol, TSH, total T3, free tetraiodothyronine (T4). Cardiovascular function, energy expenditure, and quality of life (ThyPRO-39) were assessed in patients who completed at least the 3-month visit, last measure carried-forward.ResultsTwelve patients (10 women and 2 men), age 51 ± 13.8 years (7 LT4/placebo, 5 LT4/LT3), were analyzed. No significant differences were observed in TSH. Following thyroidectomy, LT4/placebo resulted in higher free T4 + 0.26 ± 0.15 p<0.005 and lower total T3 -18 ± 9.6 ng/dl p<0.003, respectively, not observed in the LT4/LT3 group. The LT4/placebo group had a non-significant increase in body weight, +1.7 ± 3.8 Kg, total- and LDL-cholesterol +43.1 ± 72.8 and +32.0 ± 64.4 mg/dl. Conversely the LT4/LT3 group changes were -0.6 ± 1.9 Kg, -28.8 ± 49.0 and -19.0 ± 28.3 mg/dl, respectively, all non-significant. Non-significant improvement were observed in ThyPRO-39 measures in both groups, while energy expenditure, and diastolic function increased in the LT4/LT3 group.ConclusionsIn this group of patients with post-surgical hypothyroidism LT4 replacement alone does not normalize free T4 and total T3 levels and is associated with non-significant increase in weight and cholesterol. LT4/LT3 combination therapy appears to prevent these changes.Clinical Trial RegistrationClinicatrials.gov, identifier NCT05682482.