BACKGROUND
Thyrotoxicosis is a condition characterized by high levels thyroid hormone in the blood, specifically thyroxine (T4) and triiodothyronine (T3). It can occur when the thyroid gland is overactive and produces excess hormone, like in Graves’ disease or “toxic” nodules, or when the gland becomes inflamed and leaks excess thyroid hormone into the bloodstream, as in thyroiditis. Symptoms of thyrotoxicosis include tremors, a fast heartbeat (tachycardia), sweating, heat intolerance, weight loss, anxiety, and insomnia. In severe cases, it can lead to serious problems like heart failure, irregular heart rhythms, or liver failure or even a lifethreatening condition called thyroid storm.

Broadly speaking, treatment of thyrotoxicosis may include medications, surgery to remove the thyroid (thyroidectomy), or radioactive iodine therapy. Most people begin treatment with antithyroid drugs (ATDs) such as methimazole or PTU. These medications block the thyroid from making too much hormone, and they work especially well when the thyroid is overactive, as in Graves’ disease. But ATD drugs do not work when thyrotoxicosis is caused by inflammation, and sometimes they are not effective even when used correctly. When this happens, doctors may add other treatments to help lower thyroid hormone levels. One option is to use bile acid sequestrants, older drugs originally used to treat high cholesterol. Bile acid sequestrants bind bile acids in the intestine, removing them form the body and forcing the liver to convert cholesterol into new bile acids. Bile acid sequestrants also can bind other proteins, including thyroid hormones, and remove them from the body as well. They were shown in early studies to reduce T4 and T3 levels, and current guidelines recommend their use in certain situations. However, we still do not know how effective or well-tolerated this class of medication is when combined with standard antithyroid medications.

The purpose of the study is to determine whether adding bile acid sequestrants to standard hyperthyroidism treatment leads to a more rapid reduction in thyroid hormone levels than antithyroid drugs alone.

THE FULL ARTICLE TITLE
Moreno Watashi D et al. Efficacy and safety of adjunctive bile acid sequestrant therapy for thyrotoxicosis: a systematic review and meta-analysis of randomized controlled trials. Thyroid. Epub 2025 Dec 18; doi: 10.1177/10507256251409074.

SUMMARY OF THE STUDY
The researchers conducted a review of previously published clinical trials that examined whether adding a bile acid sequestrant to standard treatment for thyrotoxicosis results in a more rapid reduction in elevated thyroid hormone levels. Standard treatment included medications such as methimazole, PTU, and betablockers. After their initial literature search, they found five randomized controlled trials that met the inclusion criteria, involving 173 patients in total. Of these, 93 patients (54%) received bile acid sequestrants in addition to standard therapy, while 80 patients (46%) received standard therapy alone. Almost all patients—97 percent—had Graves’ disease. All studies were short, lasting only two to four weeks.

After the 2 week mark, there was no meaningful difference in thyroid hormone levels (between the two groups. However, in the three studies that continued for 4 weeks, the group receiving the bile acid sequestrant showed a larger, statistically significant reduction in total T3 and free T4 levels compared with the control group. Side effects were uncommon; only five patients reported mild digestive symptoms. The authors concluded that in patients with thyrotoxicosis, adding a bile acid sequestrant to standard antithyroid medication may help thyroid hormone levels return to normal more rapidly.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Although larger studies are still needed before this approach becomes widely accepted, bile acid sequestrants can be safely added to standard antithyroid medications to help lower elevated thyroid hormone levels in thyrotoxicosis, especially in Graves’ disease. Because the benefits generally appear after about four weeks, clinicians may want to start bile acid sequestrants earlier rather than later in a patient’s treatment, particularly for those with more severe thyrotoxicosis who require high doses of antithyroid drugs.

— Phillip Segal, MD

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