Surge in Desiccated Thyroid Extract Use for Hypothyroidism

CHICAGO –Prescriptions for desiccated thyroid extract (DTE) to treat newly diagnosed hypothyroidism nearly doubled between 2010 and 2020 in the United States, while prescribing of first-line levothyroxine monotherapy dropped, new research has found.

Nationwide MarketScan claims data reveals that among first-time thyroid hormone prescriptions, those for DTE rose from 5.4% in 2010 to 10.2% in 2020. At the same time, prescriptions for first-line levothyroxine dropped from 91.8% to 87.2%. Prescriptions for liothyronine (LT3), primarily in combination with levothyroxine, remained at about 2% throughout the decade.

The nonlevothyroxine therapies were more commonly prescribed in the west and southwestern United States, while levothyroxine monotherapy was more frequent in the northwest and upper midwest, and also in states with higher densities of primary care physicians and endocrinologists.

The magnitude of this shift in first-line treatment was unexpected.

"We were frankly quite surprised to see that difference in just 10 years," lead author Matthew Ettleson, MD, of the University of Chicago, Illinois, told Medscape Medical News.

Asked to comment, session moderator Elizabeth N. Pearce, MD, professor of medicine at Boston University Medical Center, Massachusetts, said she also found the dramatic shift to DTE surprising.

"It's unclear why since there hasn't been a shift in the science or in the guidelines over the last decade…I think we need to understand better what is driving this, who the patients are who are seeking it out, and which providers are the primary drivers of these prescriptions," she said.

Ettleson presented the findings at ENDO 2023: The Endocrine Society Annual Meeting. The results were simultaneously published in the Journal of Clinical Endocrinology and Metabolism.

Why the Increase in Desiccated Thyroid Extract?

Current guidelines by the American Thyroid Association (ATA) recommend levothyroxine, a synthetic form of thyroxine (T4) monotherapy, as the standard of care for treating hypothyroidism. However, approximately 10% to 20% of levothyroxine-treated patients report bothersome symptoms despite normalization of thyroid-stimulating hormone (TSH) levels.

In 2021, the ATA, along with European and British thyroid societies, issued a consensus statement noting that new trials of triiodothyronine (T3)/T4 combination therapy were "justified."

However, the MarketScan data were gathered before that statement came out, which doesn't mention desiccated thyroid extract, "so that's a bit of a head-scratcher," Ettleson said.

He said one possibility may be the existence of online materials saying negative things about levothyroxine, so that "people who are just learning about hypothyroidism might already be primed to think about alternative treatments." Moreover, some patients may view DTE as more "natural" than levothyroxine.

Ettleson also noted that the distinct geographic variation "didn't seem random…So not only was there a doubling overall but there's a variation in practice patterns across the country. I don't have an explanation for that, but I think it's important to recognize in the medical community that there are these big differences."

Endocrinologists Not as Keen to Prescribe DTE or T3

Residence in a state with higher endocrinologist density (3.0/100,000 population) was associated with a decreased likelihood of receiving T3 (adjusted odds ratio [aOR], 0.33; P < .001) or DTE therapy (aOR, 0.18; P < .001).

Residence in large central metro zones was associated with an increased likelihood of receiving T3 (aOR, 1.32; P < .001) or DTE therapy (aOR, 1.05; P < .008, respectively).

Pearce observed: "I don't see DTE in Boston. It's mostly in the south and southwest."

She said she doubted that endocrinologists were the primary prescribers of DTE, as many endocrinologists are "wary" of the pig thyroid-derived product because its T4 to T3 ratio is about 4:1, in contrast to the ratio in humans of 13-14:1.

Thus, DTE contains a much higher proportion of the active hormone T3. It is also much shorter acting, with a half-life of a few hours, compared to a few days for T4, she explained.

"We don't really know what long-term safety effects are but it's probably a less physiologic way of dosing thyroid hormone than...either levothyroxine or levothyroxine in combination with a lower T3 proportion," she said.

Just Trying to Understand

Ettleson emphasized that the goal of his research wasn't to reverse the trend but to better understand it.

Nonetheless, he also noted, "Now that we know there are more patients taking DTE, we need to start looking at rates of atrial fibrillation, fracture, heart failure, and other possible outcomes in this population and compare them with levothyroxine and nonthyroid populations to make sure that it is as safe as levothyroxine."

"There are no data to suggest increased risk, especially if TSH is monitored and stays in the normal range, but there's very little data for over 5 or 10 years on DTE-treated patients. We need the data," he emphasized.

Meanwhile, he's working on a survey of endocrinologists and non-endocrinologists to ask if they've prescribed DTE, and if so, why, and whether it's because patients asked for it.

"There's a lot more work to be done, but I think it's exciting. It's important to see how patients are being treated in the real world...and understand why it's happening and what the outcomes are."

Ettleson and Pearce have reported no relevant financial relationships.

ENDO 2023. Presented June 16, 2023.

J Clin Endocrinol. Published online June 16, 2023. Abstract

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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