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The effects of combination treatment with LT4 and LT3 on diastolic functions and atrial conduction time in LT4-treated women with low T3: a short term follow-up study

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Abstract

Purpose

To investigate the effects of combination treatment with levothyroxine (LT4) and l- triiodothyronine (LT3) on left atrial volume (LAV), diastolic functions, and atrial electro-mechanical delays in LT4-treated women with low triiodothyronine (T3) levels.

Methods

This prospective study consisted of 47 female patients between 18 and 65 years old treated at an Endocrinology and Metabolism outpatient clinic between February and April 2022 due to primary hypothyroidism. The study included patients with persistently low T3 levels in at least three measurements, despite LT4 treatment (1.6–1.8 mcg/kg/m2) for 23.13 ± 6.28 months with normal thyrotropin (TSH) and free tetraiodothyronine (fT4) levels. The combination therapy dose was as follows: the fixed LT4 dose (25 mcg) was removed from patients’ usual LT4 treatment [100 mcg (min–max, 75–150)], and a fixed LT3 dose (12.5 mcg) was added. Biochemical samples were taken, and an echocardiographic assessment was performed for patients upon their first admission, and after 195.5 ± 12.8 days of receiving LT3 (12.5 mcg) treatment.

Results

There was a statistically significant reduction at left ventricle (LV) end-systolic diameter (27.69 ± 3.14, 27.13 ± 2.89, p = 0.035), left atrial (LA) maximum volume (14.73 ± 3.22, 13.94 ± 3.15, p = 0.009), LA minimum volume (7.84 ± 2.45, 6.84 ± 2.30, p < 0.001), LA vertical diameter (44.08 ± 6.92, 34.60 ± 4.31, <0.001), LA horizontal diameter (45.65 ± 6.88, 33.43 ± 4.51, p < 0.001), LAVI (50.73 ± 18.62, 41.0 ± 13.02, p < 0.001), total conduction time (103.69 ± 12.70, 79.82 ± 18.40, p < 0.001) after LT3 replacement (respectively pre-post- treatment and p value).

Conclusion

In conclusion, the findings of this study suggest that the addition of LT3 to LT4 treatment may lead to improvements in LAVI and atrial conduction times in patients with low T3. However, further research with larger patient groups and exploration of different LT4 + LT3 dose combinations is needed to better understand the effects of combined hypothyroidism treatment on cardiac functions.

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References

  1. C.G. Roberts, P.W. Ladenson, Hypothyroidism. Lancet 363, 793–803 (2004). https://doi.org/10.1016/S0140-6736(04)15696-1

    Article  CAS  PubMed  Google Scholar 

  2. J. Jonklaas, A.C. Bianco, A.J. Bauer, K.D. Burman, A.R. Cappola, F.S. Celi et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid 24, 1670–1751 (2014). https://doi.org/10.1089/thy.2014.0028

    Article  PubMed  PubMed Central  Google Scholar 

  3. W.M. Wiersinga, L. Duntas, V. Fadeyev, B. Nygaard, M.P.J. Vanderpump, 2012 ETA guidelines: the use of L-T4 + L-T3 in the treatment of hypothyroidism. Eur. Thyroid J. 1, 55–71 (2012). https://doi.org/10.1159/000339444

    Article  PubMed  PubMed Central  Google Scholar 

  4. C. Dayan, V. Panicker, Management of hypothyroidism with combination thyroxine (T4) and triiodothyronine (T3) hormone replacement in clinical practice: a review of suggested guidance. Thyroid Res 11, 1 (2018). https://doi.org/10.1186/s13044-018-0045-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. S.J. Lee, J.G. Kang, O.H. Ryu, C.S. Kim, S. Ihm, M.G. Choi et al. The relationship of thyroid hormone status with myocardial function in stress cardiomyopathy. Eur. J. Endocrinol. 160(5), 799–806 (2009). https://doi.org/10.1530/EJE-08-0808

    Article  CAS  PubMed  Google Scholar 

  6. K. Otani, M. Takeuchi, K. Kaku, N. Haruki, H. Yoshitani, M. Tamura et al. Impact of diastolic dysfunction grade on left atrial mechanics assessed by two-dimensional speckle tracking echocardiography. J. Am. Soc. Echocardiogr. 23, 961–967 (2010). https://doi.org/10.1016/j.echo.2010.06.023

    Article  PubMed  Google Scholar 

  7. T.S.M. Tsang, M.E. Barnes, B.J. Gersh, K.R. Bailey, J.B. Seward et al. Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden. Am. J. Cardiol. 90, 1284–1289 (2002). https://doi.org/10.1016/s0002-9149(02)02864-3

    Article  PubMed  Google Scholar 

  8. A. Hosseinsabet, Assessment of atrial conduction times in patients with mild diastolic dysfunction and normal atrial size. Anatol. J. Cardiol. 15, 925–931 (2015). https://doi.org/10.5152/akd.2014.5816

    Article  PubMed  Google Scholar 

  9. M. Tadic, S. Ilic, B. Ivanovic, V. Celic, Left atrial phasic function and mechanics in women with subclinical hypothyroidism: the effects of levothyroxine therapy. Echocardiography 31, 1221–1229 (2014). https://doi.org/10.1111/echo.12554

    Article  PubMed  Google Scholar 

  10. F. Kosar, I. Sahin, N. Turan, E. Topal, Y. Aksoy, C. Taskapan et al. Evaluation of right and left ventricular function using pulsed-wave tissue Doppler echocardiography in patients with subclinical hypothyroidism. J. Endocrinol. Invest 28, 704–710 (2005). https://doi.org/10.1007/BF03347553

    Article  CAS  PubMed  Google Scholar 

  11. S. Ozturk, O. Dikbas, M. Ozyasar, S. Ayhan, F. Ozlu, D. Baltaci et al. Evaluation of left atrial mechanical functions and atrial conduction abnormalities in patients with clinical hypothyroid. Cardiol. J. 19, 287–294 (2012). https://doi.org/10.5603/cj.2012.0051

    Article  PubMed  Google Scholar 

  12. P.W. Cylde, A.E. Harari, E.J. Getka, K.M.M. Shakir, Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. JAMA 290(22), 2952–2958 (2003). https://doi.org/10.1001/jama.290.22.2952

    Article  Google Scholar 

  13. H.F. Escobar-Morreale, J. Botella-Carretero, M. Gomez-Bueno, J.M. Galan, V. Barrios, J. Sancho, Thyroid hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone. Ann. Intern Med 142, 412–424 (2005). https://doi.org/10.7326/0003-4819-142-6-200503150-00007

    Article  CAS  PubMed  Google Scholar 

  14. B. Biondi, L. Wartofsky, Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism? J. Clin. Endocrinol. Metab. 97(7), 2256–2271 (2012). https://doi.org/10.1210/jc.2011-3399

    Article  CAS  PubMed  Google Scholar 

  15. T. Rodriguez, V.R. Lavis, J.C. Meininger, A.S. Kapadia, L.F. Stafford, Substitution of liothyronine at a 1:5 ratio for a portion of levothyroxine: effect on fatigue, symptoms of depression, and working memory versus treatment with thyroxine alone. Endocr. Pr. 11(4), 223–233 (2005). https://doi.org/10.4158/EP.11.4.223

    Article  Google Scholar 

  16. P. Saravanan, H. Siddique, D.J. Simmons, R. Greenwood, C.M. Dayan, Twenty-four hour hormone profiles of TSH, Free T3 and free T4 in hypothyroid patients on combined T3/T4 therapy. Exp. Clin. Endocrinol. Diabetes 115(4), 261–267 (2007). https://doi.org/10.1055/s-2007-973071

    Article  CAS  PubMed  Google Scholar 

  17. J. Jonklaas, K.D. Burman, Daily administration of short acting liothyronine is associated with significant triiodothyronine excursions and fails to alter thyroid responsive parameters. Thyroid.: Off. J. Am. Thyroid. Assoc. 26(6), 770–778 (2016). https://doi.org/10.1089/thy.2015.0629

    Article  CAS  Google Scholar 

  18. B. Van Tassell, G.F. Wohlford, J.D. Linderman, S. Smith, S. Yavuz, Pucino et al. Pharmacokinetics of L-Triiodothyronine in patients undergoing thyroid hormone therapy withdrawal. Thyroid 29(10), 1371–1379 (2019). https://doi.org/10.1089/thy.2019.0101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. P.J.D. Owen, R. Sabit, J.H. Lazarus, Thyroid disease and vascular function. Thyroid 17, 519–524 (2007). https://doi.org/10.1089/thy.2007.0051

    Article  CAS  PubMed  Google Scholar 

  20. S.F. Nagueh, C.P. Appleton, T.C. Gillebert, P.N. Marino, J.K. Oh, O.A. Smiseth et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur. J. Echocardiogr. 10, 165–193 (2009). https://doi.org/10.1093/ejechocard/jep007

    Article  PubMed  Google Scholar 

  21. G. Acar, A. Akcay, A. Sokmen, M. Ozkaya, E. Guler, G. Sokmen et al. Assessment of atrial electromechanical delay, diastolic functions, and left atrial mechanical functions in patients with type 1 diabetes mellitus. J. Am. Soc. Echocardiogr. 22, 732–738 (2009). https://doi.org/10.1016/j.echo.2009.03.028

    Article  PubMed  Google Scholar 

  22. A.R. Cappola, L.P. Fried, A.M. Arnold, M.D. Danese, L.H. Kuller, G.L. Burke et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA 295, 1033–1041 (2006). https://doi.org/10.1001/jama.295.9.1033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. D.S. Cooper, B. Biondi, Subclinical thyroid disease. Lancet 379, 1142–1154 (2012). https://doi.org/10.1016/S0140-6736(11)60276-6

    Article  PubMed  Google Scholar 

  24. Y. Meng, T. Zhao, Z. Zhang, S. Zhang, Association between sub-clinical hypothyroidism and heart failure with preserved ejection fraction. Chin. Med J. (Engl.) 133, 364–366 (2020). https://doi.org/10.1097/CM9.0000000000000631

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, Faculty of Medicine, Pamukkale University, Denizli, Turkey

    Ipek Buber, Isik Tekin & Ismail Dogu Kilic

  2. Department of Endocrinology and Metabolism, Faculty of Medicine, Pamukkale University, Denizli, Turkey

    Ayten Eraydin & Semin Melahat Fenkci

  3. Denizli Saglik Hospital, Denizli, Turkey

    Cihan Ilyas Sevgican

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  1. Ipek Buber
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  4. Isik Tekin
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Contributions

İ.B. and A.E. were responsible for the design, management, data collection, analysis, and writing of the study. S.F. was involved in the design of the study and data collection. C.İ.S. was responsible for methodology, analysis. I.D.K. and I.T. were involved in formal analysis, supervision, writing - review, and editing. All authors read and approved the final paper.

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Correspondence to Ayten Eraydin.

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The authors declare no competing interests.

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Written informed consent was obtained from all individual participants included in the study.

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This study was conducted according to the principles of the Helsinki Declaration after it was approved by the ethical committee of Medical Faculty of Pamukkale University, Denizli, Turkiye (25.01.22/02).

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Buber, I., Eraydin, A., Sevgican, C.I. et al. The effects of combination treatment with LT4 and LT3 on diastolic functions and atrial conduction time in LT4-treated women with low T3: a short term follow-up study. Endocrine 81, 316–321 (2023). https://doi.org/10.1007/s12020-023-03363-1

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