Although levothyroxine (LT4) is recommended as the first-line treatment for hypothyroidism, a trial of combination therapy with LT4 and liothyronine (LT3) may be used for patients who have not benefited from LT4 alone, according to the findings of a review published in Thyroid.
The treatment of hypothyroidism is based on LT4, as multiple tissues are capable of thyroxine deiodination to triiodothyronine (T3), which is the active form of thyroid hormone. However, there is evidence that T3 is not fully restored in LT4-treated patients, but studies comparing therapy with LT4 vs a combination of LT4 and LT3 did not show clear differences between these modalities on mood, cognition, or quality of life. Desiccated thyroid extract is another form of combination therapy in which the LT4 to LT3 ratio is approximately 4:1.
The British Thyroid Association and the European Thyroid Association do suggest attempting combination of LT4 and LT3 in patients who have not benefited from LT4, and the American Thyroid Association and the UK National Institute for Health and Care Excellence guidelines accept this option as long as it is not used as a routine approach to treat hypothyroidism. The general suggestion for combination therapy is to reduce the LT4 dose by 25 µg/day and add 2.5 to 7.5 µg LT3 once or twice a day.
Treatment with LT3 rapidly restores euthyroidism and normalizes serum thyrotropin (TSH) in patients with hypothyroidism, but there is no clear reason as to why a patient with hypothyroidism should be treated with LT3 alone. Transient episodes of hypertriiodothyroninemia are unlikely to be common and the incidence of adverse drug reactions with LT3 treatment is not different compared with LT4 use alone.
With the use of desiccated thyroid extract, in which the LT3 to LT4 ratio is relatively higher, transiently elevated serum T3 levels above the normal reference range are more common, but there are no data from clinical trials on the occurrence of adverse drug reactions. Desiccated thyroid extract is marketed outside of formal oversight from the US Food and Drug Administration.
There are limited data on the long-term safety of combination therapy, but data collected from all published clinical trials do not suggest increased morbidity or mortality risk secondary to cardiovascular disease, atrial fibrillation, or fractures compared with LT4 treatment alone.
Treatment with LT3 alone is not common, as the doses required to normalize the TSH range are significantly higher when used alone and bring T3 levels well above the upper limit of the normal range for several hours. Data on the long-term use of LT3 alone for hypothyroidism is lacking.
“Persistent symptoms by some hypothyroid patients on [LT4] monotherapy are not uncommon and should prompt an investigation of other conditions that may present with similar symptoms,” wrote the review authors, concluding that combination therapy with LT4 and LT3 may be an option for patients who have unambiguously not benefited from LT4.
Disclosure: Two study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Idrees T, Palmer S, Maciel RMB, Bianco AC. Liothyronine and desiccated thyroid extract in the treatment of hypothyroidism [published online May 12, 2020]. Thyroid. doi:10.1089/thy.2020.0153