Rochester, MN—More than half of patients initiating levothyroxine therapy in a 10-year period failed to meet the threshold for benefit, according to a new study.

The research, published in JAMA Internal Medicine, is significant because levothyroxine is one of the most commonly prescribed drugs in the United States. In fact, about 7% of the population is estimated to have an active prescription.

Yet, point out researchers from the Mayo Clinic, Yale School of Medicine, and colleagues, no clinically relevant benefits have been established for levothyroxine replacement in terms of quality of life or thyroid-related symptoms for nonpregnant adults with subclinical hypothyroidism—thyrotropin level elevated but ≤10 mIU/L and normal free thyroxine (FT4) levels.

The authors advise that their results “suggest substantial overuse of levothyroxine during the entire duration of the study, suggesting opportunities to improve care.”

A study team sought to better understand the use of levothyroxine in the U.S. by analyzing national data for commercially insured and Medicare Advantage beneficiaries.

To do that, researchers conducted a retrospective analysis of de-identified administrative claims data linked with laboratory results from OptumLabs Data Warehouse. Included were adults with new levothyroxine prescriptions that they filled between January 1, 2008, and December 31, 2018, and who had a thyrotropin level measured within 3 months prior to levothyroxine initiation. Ultimately, the study focused on 110,842 patients who started on levothyroxine treatment between 2008 and 2018.

Using a subsample with thyrotropin and thyroxine levels available, the study team defined thyroid function as:
• Overt hypothyroidism (elevated thyrotropin and low free or total thyroxine [FT4 or T4] levels)
• Subclinical hypothyroidism (elevated thyrotropin and normal FT4 or T4 levels)
• Normal thyroid function (normal thyrotropin and FT4 or T4 levels)

Also analyzed were mild subclinical hypothyroidism (thyrotropin level of 4.5 mIU/L to <10 mIU/L with normal FT4 or T4), moderate subclinical hypothyroidism (thyrotropin level of 10-19.9 mIU/L), and severe subclinical hypothyroidism (thyrotropin level >19.9 mIU/L).

Median thyrotropin level at treatment initiation did not significantly change: 5.8 mIU/L in 2008 to 5.3 mIU/L in 2018, the authors note, adding that, in the subset of 58,706 patients with thyrotropin and FT4 or T4 levels available, levothyroxine was initiated for overt hypothyroidism (4,948 [8.4%]), subclinical hypothyroidism (35,814 [61.0%]), and normal thyroid levels (17,944 [30.5%]).

Results indicate that, during the 10-year period, the proportion of adults with overt hypothyroidism increased (7.6% to 8.4%; P = .02); the proportion with subclinical hypothyroidism did not change (59.3% to 65.7%; P = .36); and the proportion with normal thyroid function did not change (32.9% to 26.2%; P = .84).

Among patients with subclinical hypothyroidism, meanwhile, no significant change was documented in patients with mild subclinical hypothyroidism (48.2% to 57.9%; P = .73) and moderate subclinical hypothyroidism (8.5% to 6.4%; P = .16), while the proportion with severe subclinical hypothyroidism decreased (2.5% to 1.3%; P = .02).

“We found that levothyroxine treatment was commonly initiated for mildly increased thyrotropin levels, and this did not change significantly over time,” the researchers write. “Among patients for whom full thyroid function test results were available, 60% initiated levothyroxine for treatment of subclinical hypothyroidism (mostly for mild subclinical hypothyroidism) and 30% for normal thyroid function, without significant change in these patterns over time.”

The authors emphasize that the practice “is at odds with evidence demonstrating no significant association of levothyroxine replacement with measures of health-related quality of life, thyroid-related symptoms, depressive symptoms, fatigue, or cognitive function.”

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