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Levothyroxine Overused for Less Severe Hypothyroidism

— Few new prescriptions were for patients with overt hypothryoidism, researchers found

MedpageToday
A photo of a bottle of levothyroxine.

Levothyroxine was overprescribed for patients with subclinical hypothyroidism during the past decade, a new study found.

Of patients in an insurance database with available data on thyrotropin and FT4 or T4 levels available from 2008 to 2018, the majority who were newly prescribed levothyroxine had subclinical hypothyroidism (61%), largely mild subclinical hypothyroidism, while far fewer had overt hypothyroidism (8.4%), Juan Brito, MD, MSc, of the Mayo Clinic in Rochester, Minnesota, and colleagues wrote in a research letter appearing in .

Interestingly, 30.5% of patients with these labs available were started on levothyroxine with normal thyroid levels.

During this time, the median thyrotropin level that prompted prescribing clinicians to write a script for levothyroxine remained generally the same, holding around 5.8 mIU/L in 2008 and 5.3 mIU/L in 2018 (P=0.79).

However, there was no significant change in the proportion of patients with subclinical hypothyroidism from 2008 to 2018 (59.3% to 65.7%, P=0.36).

Of note, 60% of patients in this study newly initiated on levothyroxine were given the prescription from a primary care provider, while only 11% were started on this treatment by an endocrinologist.

"Frequent initiation of levothyroxine in these patients 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," Brito's group pointed out.

Current recommend against initiating levothyroxine treatment for nonpregnant adults with subclinical hypothyroidism, defined as a thyrotropin level elevated but 10 mIU/L or less and normal free thyroxine (FT4) levels, due to a lack of quality of life benefit.

A retrospective analysis of Medicare Advantage and commercial insurance claims data found a total of 110,842 adults ages 18 and older filled new levothyroxine prescriptions from 2008 to 2018.

The number of people with normal thyroid functioning didn't significantly change (32.9% to 26.2%, P=0.84), though there was a significant difference in the number of adults with overt hypothyroidism (7.6% to 8.4%, P=0.02).

As for other changes, the number of patients with severe subclinical hypothyroidism significantly decreased from 2008 to 2018 (2.5% to 1.3%, P=0.02). On the other hand though, the number of patients with mild subclinical hypothyroidism (48.2% to 57.9%, P=0.73) and those with moderate subclinical hypothyroidism (8.5% to 6.4%, P=0.16) didn't see any significant changes during this decade.

"[This study] highlights enormous overuse of levothyroxine," wrote authors William Silverstein, MD, of the University of Toronto in Canada, and Deborah Grady, MD, MPH, of the University of California, San Francisco.

"While it is unclear as to why a significant proportion of patients with normal thyrotropin values were prescribed levothyroxine, much of the impetus to treat subclinical hypothyroidism comes from observational studies suggesting an association between subclinical hypothyroidism and cardiac complications, including coronary events and congestive heart failure," they suggested.

Continuing, they echoed what Brito's group pointed out in their study, saying that current randomized clinical trial data continue to show no real symptom benefit for levothyroxine treatment in subclinical hypothyroidism.

"While treating subclinical hypothyroidism has no benefit, it can predispose to harm," the editorialists warned, stating that long-term levothyroxine therapy has been linked to an increased risk for cardiovascular disease, cardiac dysrhythmias, osteoporosis, and fractures, not to mention also higher healthcare costs and pill burden on the patient.

They suggested implementing "decision aids" into electronic health records based on thyroid lab values, as well as blocking prescriptions in inappropriate cases. Silverstein and Grady also suggested changing the thyrotropin reference range to make only values greater than 10 mIU/L read as "abnormal."

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    Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures

The study was supported by the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota.

Brito reported no disclosures.

Other co-authors reported support from the NIH, as well as various ties to industry.

Silverstein and Grady reported no disclosures.

Primary Source

JAMA Internal Medicine

Brito JP, et al "Levothyroxine Use in the United States, 2008-2018" JAMA Intern Med 2021l; DOI: 10.1001/jamainternmed.2021.2686.

Secondary Source

JAMA Internal Medicine

Silverstein WK & Grady D "Overuse of Levothyroxine in Patients With Subclinical Hypothyroidism Time to "Leve"-Out-Thyroxine" JAMA Intern Med 2021; DOI: 10.1001/jamainternmed.2021.2690.