BACKGROUND
Hypothyroidism is common and is diagnosed by elevated levels of TSH and low levels of thyroxine (T4). T4 is the main hormone secreted from the thyroid gland. T4 is converted to the active thyroid hormone, T3, mostly in peripheral tissues. Most, if not all, of the actions of the thyroid are mediated by T3. Symptoms of hypothyroidism are also very common and nonspecific, including fatigue/ decreased energy, difficulty concentrating, weight gain, feeling cold and constipation. The standard of care for the treatment of hypothyroidism is synthetic thyroxine (L-T4) administered at doses to normalize TSH levels. The expectation is that T3 levels will also be returned to normal by the conversion of L-T4 to T3.

While L-T4 monotherapy is effective in relieving symptoms in most hypothyroid patients, ~10% of patients continue to have symptoms that they attribute to hypothyroidism. Because of this, alternative treatment options are proposed, including combining levothyroxine with T3 (combination T4/T3 therapy) and desiccated thyroid extract (DTE), produced from animal thyroid gland that also contain T4 and T3. DTE was the only treatment for hypothyroidism until thyroxine was isolated and able to be mass produced. Some studies have reported better outcomes with T4/ T3 combination therapy as comparted to levothyroxine monotherapy, although this has been inconsistently demonstrated and thus remains controversial.

The goal of this study was to review and analyze the results of clinical trials that evaluated patient preference in adults with hypothyroidism comparing treatments using L-T4 monotherapy with those using T4 and T3 in the form of either T4/T3 combination therapy or DTE.

THE FULL ARTICLE TITLE
de Lima Beltrão FE et al Treatment preferences in patients with hypothyroidism: an analysis of eleven randomized controlled trials. J Clin Endocrinol Metab. Epub 2024 Sep 18:dgae651; doi: 10.1210/clinem/dgae651. PMID: 39290156.

SUMMARY OF THE STUDY
A total of 11 clinical trials were included, with a total of 1135 patients (543 on L-T4 and 592 on combination therapy). Overall, the majority of these studies (6 of 11) showed no difference between the treatment groups while 5/11 showed a preference for combination therapy. Combining all of the studies together (call a meta-analysis) suggested there was an overall preference for combination therapy over L-T4 monotherapy. Overall, 52% of patients preferred combination therapy (T4/T3 or DTE), 24% preferred L-T4 monotherapy, and 24% had no preference.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This meta-analysis of 11 clinical trials of treatment options for hypothyroidism suggests that a slight majority of patients preferred combination therapy that included some form of T4 and T3. This is valuable insight as we continue to try to provide the best options for treating patients with hypothyroidism. This also provides options to address the continued symptoms of ~10% of hypothyroid patients who do not feel completely well on L-T4 monotherapy.

— Alan P. Farwell, MD

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