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Randomized Controlled Trial
. 2025 Mar 10:16:1522753.
doi: 10.3389/fendo.2025.1522753. eCollection 2025.

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

Giao Q Phan  1 , Sahzene Yavuz  2 , Angeliki M Stamatouli  3 , Ritu Madan  3 , Shanshan Chen  3 , Amelia C Grover  4 , Naris Nilubol  5 , Pablo Bedoya  6 , Cory Trankle  7 , Roshanak Markley  7 , Antonio Abbate  8 , Francesco S Celi  9
Affiliations
Randomized Controlled Trial

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

Giao Q Phan et al. Front Endocrinol (Lausanne). .

Abstract

Context: Despite 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).

Objective: Feasibility trial LT4/liothyronine (LT3) combination vs. LT4/placebo in post-surgical hypothyroidism.

Design: Double-blind, placebo-controlled, 24-week study.

Setting: Academic medical center.

Patients: Individuals with indications for total thyroidectomy and replacement therapy.

Interventions: LT4/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 measures: Changes 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.

Results: Twelve 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.

Conclusions: In 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 registration: Clinicatrials.gov, identifier NCT05682482.

Keywords: clinical trial; combination therapy; hypothyroidism; levothyroxine; liothyronine; post-surgical hypothyroidism.

PubMed Disclaimer

Conflict of interest statement

FSC has served as consultant for IBSA Institut Biochimique and Alora pharmaceuticals. Both companies produce thyroid medication. None of these companies nor their products have been involved in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Study scheme and procedures.
Figure 2
Figure 2
CONSORT chart. The analysis was conducted (last measure carried forward) on study participants who completed the three-month visit.
See this image and copyright information in PMC

References

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