Liothyronine Improved Persistent Hypothyroidism Symptoms Despite Optimum Levothyroxine Therapy

Doctor showing thyroid gland models at table in hospital, closeup
Investigators evaluated the effect of treatment with liothyronine on quality of life in female patients with hypothyroidism and thyroid-stimulating hormone levels within reference ranges.

Liothyronine (LT3) monotherapy was found to improve hypothyroid symptoms and quality of life (QOL) among women who experienced residual symptoms while undergoing treatment with levothyroxine (LT4) monotherapy or LT3/LT4 combination therapy, according to the results of a study published in Frontiers in Endocrinology.

This study was conducted between 2018 and 2020 at the Oslo University Hospital. Women (N=59) with hypothyroidism and residual disease symptoms despite optimal LT4 treatment were randomly assigned to receive LT4 and LT3 monotherapy in a nonblinded, crossover design for 12 weeks each. Patients who were on LT3/LT4 combination therapy had a 4-week LT4 monotherapy run-in period. Thyroid-stimulating hormone (TSH) levels were assessed every 4 weeks, and dosing was adjusted, if necessary. The ThyPRO, 36-item short form (SF-36), and Fatigue Questionnaire instruments were used to assess QOL.

The mean age of the population was 42.9±9.7 years at baseline and 30.6±10.2 years at diagnosis of hypothyroidism. Patients had been receiving treatment with LT4 monotherapy for 10.6±7.0 years, 94.9% had idiopathic hypothyroidism, body mass index (BMI) was 28.1±5.6 kg/m2, median TSH level was 0.64 (interquartile range [IQR], 0.26-1.60) mU/L, free thyroxine level was 16.8 (IQR, 14.7-19.0) pmol/L, free triiodothyronine level was 4.4 (IQR, 3.8-4.9) pmol/L, and testing for thyroid peroxidase antibodies was positive in 52.% of study participants.

During LT3 monotherapy treatment, physical (mean difference [MD], -4.0 points; P <.001) mental (MD, -1.8 points; P <.001), and total (MD, -5.8 points; P <.001) fatigue scores decreased significantly from baseline. No changes were observed while the patients were on LT4 monotherapy. Physical, mental, and total fatigue scores decreased by 3.2, 1.2, and 4.4 points after switching from LT4 monotherapy to LT3 monotherapy (all P ≤.004), respectively.

Similarly, during LT3 monotherapy, patients reported improved physical functioning, role-physical, general health, vitality, social functioning, role-emotional, and mental health scores (all P ≤.018). No changes were reported during LT4 monotherapy. Switching from LT4 monotherapy to LT3 monotherapy was found to be associated with significant changes to vitality (MD, 11 points; P =.001), social functioning (MD, 11 points; P =.004), and mental health (MD, 8 points; P <.001) scores.

Symptoms of goiter, hyperthyroidism, hypothyroidism, eye, tiredness, cognitive complaints, anxiety, depression, emotional susceptibility, impaired social life, impaired daily life, and overall QOL significantly improved on LT3 monotherapy (all P ≤.017). Monotherapy with LT4 was associated with significant improvements in cognitive complaints, impaired daily life, and cosmetic complaints (all P ≤.022).

No significant trends were observed for the safety parameters of resting heart rate or systolic and diastolic blood pressures.

This study was limited by not blinding patients to their therapy. Also, as all patients had previously undergone treatment with LT4, they may have been biased toward the LT4 monotherapy treatment.

These data indicated that LT3 monotherapy improved QOL and hypothyroidism symptoms without causing adverse cardiovascular effects. Additional, long-term studies are needed to evaluate LT3 monotherapy as a potential treatment for women with hypothyroidism.


Bjerkreim BA, Hammerstad SS, Gulseth HL, et al. Effect of liothyronine treatment on quality of life in female hypothyroid patients with residual symptoms on levothyroxine therapy: a randomized crossover study. Front Endocrinol. 2022;13:816566. doi:10.3389/fendo.2022.816566