Thyroid Signaling Biomarkers in Female Symptomatic Hypothyroid Patients on Liothyronine versus Levothyroxine Monotherapy: A Randomized Crossover Trial

Betty Ann Bjerkreim; Sara Salehi Hammerstad; Hanne Løvdal Gulseth; Tore Julsrud Berg; Sindre Lee-Ødegård; Erik Fink Eriksen

doi:10.1155/2022/6423023

Thyroid Signaling Biomarkers in Female Symptomatic Hypothyroid Patients on Liothyronine versus Levothyroxine Monotherapy: A Randomized Crossover Trial

J Thyroid Res. 2022 May 4:2022:6423023. doi: 10.1155/2022/6423023. eCollection 2022.

Authors

Betty Ann Bjerkreim^{1

2}, Sara Salehi Hammerstad^{3

4}, Hanne Løvdal Gulseth⁵, Tore Julsrud Berg^{1

2}, Sindre Lee-Ødegård⁶, Erik Fink Eriksen^{3

7}

Affiliations

¹ Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
² Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Pilestredet Park Specialist Center, Oslo, Norway.
⁴ Department of Pediatrics, Oslo University Hospital, Oslo, Norway.
⁵ Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway.
⁶ Department of Transplantation, Oslo University Hospital, Oslo, Norway.
⁷ The Faculty of Dentistry, University of Oslo, Oslo, Norway.

Abstract

Background: Levels of thyroid-stimulating hormone (TSH) are believed to reflect degree of disease in patients with hypothyroidism, and normalization of levels is the treatment goal. However, despite adequate levels of TSH after starting levothyroxine (LT4) therapy, 5-10% of hypothyroid patients complain of persisting symptoms with a significant negative impact on quality of life. This indicates that TSH is not an optimal indicator of intracellular thyroid hormone effects in all patients. Our aim was to investigate different effects of LT3 and LT4 monotherapy on other biomarkers of the thyroid signaling pathway, in addition to adverse effects, in patients with residual hypothyroid symptoms.

Methods: Fifty-nine female hypothyroid patients, with residual symptoms on LT4 monotherapy or LT4/liothyronine (LT3) combination therapy, were randomly assigned in a non-blinded crossover study and received LT4 or LT3 monotherapy for 12 weeks each. Measurements, including serum analysis of a number of biochemical and hormonal parameters, were obtained at the baseline visit and after both treatment periods.

Results: Free thyroxine (FT4) was higher in the LT4 group, while free triiodothyronine (FT3) was higher in the LT3 group. The levels of reverse triiodothyronine (rT3) decreased after LT3 treatment compared with LT4 treatment. Both low-density lipoprotein (LDL) and total cholesterol levels were reduced, while sex hormone-binding globulin (SHBG) increased after LT3 treatment compared with LT4 treatment. The median TSH levels for both treatment groups were within the reference range, however, lower in the LT4 group than in the LT3 group. We did not find any differences in pro-B-type natriuretic peptide (NT pro-BNP), handgrip strength, bone turnover markers, or adverse events between the two treatment groups.

Conclusion: We have demonstrated that FT4, FT3, rT3, cholesterol, and SHBG show significantly different values on LT4 treatment compared with LT3 treatment in women with hypothyroidism and residual symptoms despite normal TSH levels. No differences in general or bone-specific adverse effects were demonstrated. This trial is registered with NCT03627611 in May 2018.

Associated data

ClinicalTrials.gov/NCT03627611