Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 23:40:100395.
doi: 10.1016/j.jcte.2025.100395. eCollection 2025 Jun.

Treatment of hypothyroidism with the combination of levothyroxine and slow-release triiodothyronine: a randomized clinical trial

F Azizi  1 , A S Moeini  1 , L Mehran  1 , S Masoumi  1 , H Abdi  1 , S M Foroutan  2 , A E Saghafinia  3 , A Amouzegar  1
Affiliations

Treatment of hypothyroidism with the combination of levothyroxine and slow-release triiodothyronine: a randomized clinical trial

F Azizi et al. J Clin Transl Endocrinol. .

Abstract

Background: Some patients with hypothyroidism lack satisfaction with levothyroxine (LT4) monotherapy, which may be related to lower serum triiodothyronine (T3) and T3/T4 ratios compared to control individuals. This study aimed to evaluate the efficacy and safety of a combination therapy of slow-release T3 (SRT3) and LT4 in patients with primary hypothyroidism compared with LT4 monotherapy.

Methods: Thirty-two hypothyroid women were randomized into two groups of SRT3 + LT4 combination and LT4 monotherapy. Group one received a combination of 15 µg SRT3 and 75 µg LT4, and group two received 100 µg LT4 daily for 8 weeks. Clinical and biochemical measurements were performed at baseline and 4 to 8 weeks after intervention.

Results: There were no significant changes in serum levels of fT4, T3, TSH, and T3/fT4 ratio in the LT4 group at the end of 4 to 8 weeks of study. A statistically significant decrease in fT4 and TSH, and an increase in serum T3 and the T3/fT4 ratio, were observed in the SRT3 + LT4 group. The T3/fT4 ratio reached comparable values to those in normal subjects, 93.63 ± 23.25 vs 95.06 ± 19.44 ng/ng, respectively. The rise in the T3/fT4 ratio 8 weeks after SRT3 + LT4 treatment was between 21 % and 90 % in 10 patients and 1 % and 13 % in 5 patients, with no change in one patient.

Conclusion: The novel combination of SRT3 + LT4 therapy resulted in a significant increase in serum T3 and the T3/fT4 ratio in hypothyroid patients compared to those receiving LT4 monotherapy. The rise in the T3/fT4 ratio was ≥ 21 % in two-thirds of patients; the lack of a significant increase in the T3/fT4 ratio in some patients during SRT3-LT4 combination therapy demands further investigation.

Keywords: Hypothyroidism; Levothyroxine; Slow-release; Triiodothyronine.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Mean changes in serum concentrations of T3, fT4, TSH, and T3/fT4 ratio in SRT3 + LT4 and LT4 monotherapy groups before, and 4 and 8 weeks after intervention; P < 0.001, compared to LT4 monotherapy.
Fig. 2
Fig. 2
Mean T3/fT4 ratio in patients treated with SRT3 + LT4 combination or LT4 monotherapy at baseline and 4 and 8 weeks after the intervention. The right end column shows the mean T3/fT4 ratio in normal subjects.
Fig. 3
Fig. 3
Change in T3/fT4 ratio at week 8 in patients treated with SRT3 + LT4 combination (A and C) and after T4 monotherapy (B and D). Each bar represents an individual patient. Panels A and B show changes in the T3/fT4 ratio (ng/ng) and panels C and D demonstrate a percent change of the T3/fT4 ratio from the baseline. SRT3: slow release triiodothyronine; LT4: levothyroxine.
See this image and copyright information in PMC

References

    1. Braverman L.E., Ingbar S.H., Sterling K. Conversion of thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects. J Clin Invest. 1970;49(5):855–864. - PMC - PubMed
    1. McAninch E.A., Bianco A.C. The History and Future of Treatment of Hypothyroidism. Ann Intern Med. 2016;164(1):50–56. - PMC - PubMed
    1. Jonklaas J., Bianco A.C., Bauer A.J., Burman K.D., Cappola A.R., Celi F.S., et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid : official journal of the American Thyroid Association. 2014;24(12):1670–1751. - PMC - PubMed
    1. Saravanan P., Chau W.-F., Roberts N., Vedhara K., Greenwood R., Dayan C.M. Psychological well-being in patients on ‘adequate’ doses of l-thyroxine: results of a large, controlled community-based questionnaire study. Clin Endocrinol. 2002;57(5):577–585. - PubMed
    1. Wekking E.M., Appelhof B.C., Fliers E., Schene A.H., Huyser J., Tijssen J.G., et al. Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism. Eur J Endocrinol. 2005;153(6):747–753. - PubMed

LinkOut - more resources