BACKGROUND
The thyroid gland produces 2 thyroid hormones: thyroxine (T4) and triiodothyronine (T3). T4 is the main hormone secreted by the thyroid gland. T4 is converted outside of the thyroid to T3, which is the active hormone. The thyroid also secretes small amounts of T3 under normal conditions. Hypothyroidism, or underactive thyroid, is common and is typically treated with levothyroxine (L-T4) a synthetic form of T4. Most patients with hypothyroidism do fine with L-T4 alone and their symptoms are resolved. However, some patients report persistent symptoms on T4 alone even though their thyroid levels may be back in the normal range. This led to considering adding liothyronine (L-T3) to replace the small amounts of T3 that the thyroid used to secrete in combination with L-T4 in hypothyroid patients. Although the studies comparing the use of combined L-T4 and L-T3 as compared to L-T4 alone in hypothyroid patients have not shown clinically measurable differences, some patients prefer the combination therapy.

A concern with using L-T3 is that it does not last 24 hours in the blood. Also, it may not be safe for the heart and bones. This study tries to answer the question about the safety of the use of L-T3 in hypothyroid patients.

THE FULL ARTICLE TITLE
Bahl S, et al. Risk of death and adverse effects in patients on liothyronine: a multisource systematic review and meta-analysis. The Journal of Clinical Endocrinology & Metabolism, Volume 110, Issue 11, November 2025, 3278–3288, PMID: 40795305.

SUMMARY OF THE STUDY
The authors looked at 25 published studies and 27 reports of cases using L-T3 for the treatment of hypothyroidism. Among the reports, there were serious cases of thyrotoxicosis (high thyroid hormone levels) including 2 deaths. A total of 14 of those cases were due to unapproved use of L-T3 for weight loss or fatigue and 10 cases were due to dispensing errors including by compounding pharmacies. Some of the compounding errors involved dispensing as much as 1000 times the usual treatment doses of L-T3. Among the studies comparing L-T4/L-T3 with L-T4 alone, although difficult to compare due to the varied population looked at, there were no ill effects or increased risk of abnormal heart rhythms. Adverse effects of L-T3 to the bone were not studied.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The results of this study appear reassuring in that the use of L-T3 at the usual doses for the treatment of hypothyroid patients is safe. This study also points out that treatment with high amounts of L-T3, due to dispensing errors from compounding pharmacies or from off-label and unapproved uses, like weight loss and fatigue, can cause harm and should be avoided.

— Susana Ebner, MD

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