- Under physician supervision, 26% of older adults successfully stopped levothyroxine while maintaining stable thyrotropin and free thyroxine levels for a year.
- Discontinuation was more common in patients taking lower levothyroxine doses at baseline.
- Researchers urged clinicians to reassess thyroid therapy in older adults to avoid overtreatment and its associated risks.
A quarter of older adults on hypothyroidism medication were able to wean off of it while maintaining adequate thyroid function, an open-label prospective study showed.
In patients 60 and up, a protocol for stepwise reduction in levothyroxine led to 25.7% successfully discontinuing the medication while maintaining a thyrotropin (TSH) level under 10 mIU/L and a free thyroxine level within the reference range, reported Rosalinde Poortvliet, MD, PhD, of Leiden University Medical Center in the Netherlands, and colleagues.
These patients maintained a median TSH level of 5.03 mIU/L and a mean free thyroxine level of 1.01 ng/dL after 1 year. Nearly half (48.4%) maintained a thyrotropin level under 4.8 mIU/L, the team detailed in JAMA.
A lower levothyroxine dose at baseline predicted successful discontinuation, with nearly two-thirds (63.6%) of patients on a daily dose of 50 µg or less able to stop treatment.
Levothyroxine is often continued indefinitely because current guidelines lack deprescribing protocols, according to the study authors. This persists even though hypothyroidism can be transient, with subclinical cases often reverting to normal thyroid function in older adults.
The new findings show that "carefully selected patients aged 60 years or older may not require lifelong levothyroxine treatment and could benefit from a supervised trial of discontinuation, particularly in those taking a dose of 50 µg/d or lower," Poortvliet told MedPage Today.
Levothyroxine ranks in the top three most commonly dispensed medications in the U.S., and older age is a predictor of initiation, noted Maria Papaleontiou, MD, of the University of Michigan in Ann Arbor, and Anne Cappola, MD, of the University of Pennsylvania in Philadelphia.
"Up to 60% of adults are prescribed levothyroxine for subclinical hypothyroidism ... or for non-evidence-based indications," the duo wrote in an accompanying editorial.
Overtreatment with levothyroxine is a growing concern, with past research linking longer-term use to increased risks for fractures, atrial fibrillation, and cognitive disorders, as well as all-cause and cardiovascular mortality.
"Clinicians should reassess the necessity of thyroid hormone therapy to minimize overtreatment and its associated risks, embracing a strategy of patient-centered, evidence-based deprescribing," advised Papaleontiou and Cappola.
"In parallel, clinicians need clear, straightforward guidance on when to prescribe levothyroxine. Prevention of inappropriate levothyroxine prescribing would significantly reduce the need to consider deprescribing. When an initial thyrotropin test is elevated in a nonpregnant adult, the first step is to repeat the test," they added.
The open-label, prospective study followed 370 community-dwelling adults at primary care practices in the Netherlands from January 2020 to December 2023.
Inclusion required a stable levothyroxine dose (≤150 µg per day) for at least 1 year with TSH levels under 10 mIU/L. Exclusion criteria included a history of thyroidectomy, radioactive iodine treatment, neck irradiation, and congenital or secondary hypothyroidism.
The study cohort had a median age of 70, and 80% were women. At baseline, the median TSH level was 2.20 mIU/L, and free thyroxine averaged 1.21 ng/dL. The average levothyroxine dose was 84 µg per day.
The protocol called for general practitioners to review TSH and free thyroxine levels at each visit and reduce the levothyroxine dose if the TSH level was less than 10 mIU/L and free thyroxine level was greater than or equal to the lower limit of the reference range. When those criteria were met, the doctor cut the dose by 12.5 μg to 50 μg per day at baseline, 25 μg to 38 μg per day after 6 and 12 weeks, and 25 μg per day after 18, 24, and 30 weeks. Thyroid function testing was performed at least 6 weeks after each dose reduction.
Among the participants who remained on the medication, most ceased dose reductions because their TSH levels rose to 10 mIU/L or above.
While a TSH threshold of 10 mIU/L "may be reasonable" after levothyroxine discontinuation, Papaleontiou and Cappola pointed out that some clinicians and patients may not be comfortable with TSH levels exceeding the reference range to that extent.
"It has been suggested that treatment with levothyroxine may be considered in patients aged 65 years or older with subclinical hypothyroidism (TSH range 7.0-9.9 mIU/L) based on observational data supporting an increased risk of mortality from coronary heart disease in this TSH range," they noted.
Thyroid-related quality of life didn't differ significantly between those who successfully discontinued the drug and those who didn't.
A total of 17 serious adverse events occurred (15 unplanned hospitalizations and two deaths), but none were considered related to the study intervention.
There was a lack of data regarding the indication for levothyroxine treatment and measurement of thyroid peroxidase antibodies, Poortvliet's group noted, which limits the translation of the results to specific subgroups.
Disclosures
The RELEASE trial was supported by research grant from ZonMw for the Primary Care and Elderly Care program.
Poortvliet and co-authors reported no disclosures.
Papaleontiou and Cappola reported no disclosures.
