Role of Liothyronine and Desiccated Thyroid Extract in Hypothyroidism

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.

Reference

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