Examining T4/T3 Combination Therapy in Hypothyroidism

CHICAGO — Levothyroxine (LT4) monotherapy remains the standard treatment for hypothyroidism, although a subset of patients continue to have hypothyroidism despite normal thyroid-stimulating hormone (TSH) and serum-free thyroxine levels. LT4 and liothyronine (LT3) combination therapy to improve hypothyroidism remains a topic of interest.

A clinical session at the recent American Thyroid Association (ATA) 2024 Meeting explored LT4/LT3 combination therapy. Speakers addressed the biochemical and clinical differences between monotherapy and combination therapy. Take-home messages included that combination treatment is both safe and effective and is preferred by many patients. Additionally, attendees heard an update on the Joint British Thyroid Association guidelines on the use of LT3 in hypothyroidism.

The thyroid system is “wired” to defend serum T3 and in the absence of a fully functional thyroid gland, patients rely only on the deiodinases, Antonio C. Bianco, MD, PhD, of The University of Texas Medical Branch in Galveston, Texas, told attendees. 

Bianco referred attendees to his recent article in The Journal of Clinical Endocrinology & Metabolism, which examined data from the Longitudinal Study of Adult Health in Brazil (ELSA-Brazil) study. Bianco and his coauthors analyzed data from 186 participants who started treatment with LT4 during the study and 243 subjects continuously treated with LT4 therapy. The more recent LT4 participants experienced an 11%-19% decrease in TSH, an approximately 19% increase in free T4 (FT4), and a 7% reduction in free T3 (FT3) serum levels.

Approximately 40% of the recent LT4 patients had declines of FT3 > 10%, said Bianco. “This was associated with an increase in triglyceride levels and the use of hypolipidemic and antidiabetic medications,” he said. “Participants continuously treated with LT4 showed a stable elevation in serum FT4 and a reduction in serum FT3 and TSH levels.”