A Third Discontinuing Levothyroxine Have Normal Thyroid Levels

Nancy A. Melville

February 04, 2021

Approximately a third of patients treated for hypothyroidism continue to maintain normal thyroid levels after discontinuing thyroid hormone replacement therapy.

Those who were treated for overt hypothyroidism were less likely to maintain normal hormone levels than those with subclinical disease, the new meta-analysis shows.

"This analysis is the first to summarize the limited evidence regarding successful thyroid hormone discontinuation, but unfortunately more research is needed to develop an evidenced-based strategy for deprescribing thyroid hormone replacement," Nydia Burgos, MD, and colleagues write in their article published online in Thyroid.

Nevertheless, the main findings were somewhat surprising, Burgos, of the School of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Puerto Rico, told Medscape Medical News.

"I expected that a considerable portion of patients would remain euthyroid, but up to a third of patients was an impressive number," she said.

The finding could be an indicator of people who may not have had much benefit from the treatment in the first place, she noted.

"The truth of the matter is that levothyroxine (LT4) is among the top prescribed drugs in the United States, and every day in clinics we encounter patients that were started on thyroid hormone replacement therapy for unclear reasons, as a therapeutic trial that was never reassessed, or as treatment for subclinical hypothyroidism without having convincing criteria for treatment," she observed.

Meta-Analysis of 17 Studies Examining LT4 Discontinuation 

Known to be highly effective in the treatment of overt hypothyroidism, LT4 is often prescribed long term; however, it is also commonly prescribed for patients with subclinical hypothyroidism, despite research suggesting no benefits in these patients.   

With a guideline panel underscoring the lack of evidence and issuing a "strong recommendation" in May 2019 against treatment with thyroid hormones in adults with subclinical hypothyroidism (elevated thyroid-stimulating hormone [TSH] levels and normal free T4 levels), clinicians may increasingly be considering discontinuation strategies.

To examine the evidence to date on the clinical outcomes of discontinuing LT4, Burgos and colleagues conducted their meta-analysis in which they identified 17 observational studies that met the inclusion criteria. Of a total of 1103 patients in the studies, 86% were women. Most studies only included adults.

With a median follow-up of 5 years, the pooled estimate of patients maintaining euthyroidism after treatment discontinuation was 37.2%.

The estimated rate of remaining euthyroid was significantly lower among those with overt hypothyroidism (11.8%) compared to those with subclinical hypothyroidism (35.6%).

Meanwhile, as many as 65.8% of patients ended up restarting thyroid hormone treatment during the follow-up period, according to pooled estimates, and the rate was as high as 87.2% in patients with overt hypothyroidism. The mean increase in TSH from time of LT4 discontinuation to follow-up was 9.4 mIU/L.

Among specific factors shown to be linked to a lower likelihood of euthyroidism at follow-up were inconsistent echogenicity on thyroid ultrasound, elevated TSH (8-9 mIU/L), and the presence of thyroid antibodies.

Only a few of the studies evaluated thyroid hormones other than synthetic LT4 (such as the commonly used desiccated thyroid), and so the analysis did not compare differences between therapies, Burgos noted.

Despite the lack of evidence of benefits of LT4 treatment for subclinical hypothyroidism, the finding that even among those patients approximately two thirds were not euthyroid at follow-up was not unexpected, she added.

"I am not surprised that even in the subclinical hypothyroidism group about two thirds of participants were not euthyroid, because when looking at the natural history of subclinical hypothyroidism in other studies, only a fifth had normalized thyroid hormone tests, while the majority continue with mild subclinical hypothyroidism and a fifth progress to overt hypothyroidism," she explained.

More Work Needed to Determine Best Way to Taper Down LT4

The specific regimens for discontinuing LT4 were detailed in only three studies and reflected varying approaches, ranging from tapering down the dose over 2 weeks to reducing the dose over several more weeks, or even months, Burgos noted

"We need more studies to figure out which tapering regimen will promote a more favorable outcome," she said.

"The ideal regimen will be one in which patients can comply with follow-up visits and have thyroid function testing done before symptoms of hypothyroidism develop."

In addition to likely offering no benefit to people with subclinical hypothyroidism, other reasons for discontinuing LT4 in patients who are considered appropriate candidates include concerns about side effects in older patients.

The authors say there is evidence indicating that as many as 50% of patients older than 65 who take thyroid hormones develop iatrogenic hyperthyroidism, which can have detrimental effects including an increased risk for cardiac arrhythmias, angina pectoris, bone loss, and fractures.

Collaborative Approach to "Deprescribing" Suggested

To get patients off LT4, the authors suggest a collaborative approach of "deprescribing," whereby the healthcare professional supervises with a goal of managing polypharmacy and improving outcomes.

"This systematic process starts with an accurate evaluation of the medication list, followed by identification of potentially inappropriate medications, collaboration between patients and clinicians to decide whether deprescribing would be appropriate, and establishing a supportive plan to safely deprescribe the medication," they write.

When decision-making is shared, patients are more likely to consider discontinuation if they understand why the medication is inappropriate, have their concerns related to the discontinuation addressed, understand the process, and feel that they have the support of the clinical team, the authors conclude.

The authors have reported no relevant financial relationships.

Thyroid. Published online December 29, 2020. Abstract

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