1 in 3 on Levothyroxine Take Meds That Interfere With Thyroid Tests

Nancy A. Melville

March 21, 2021

Approximately a third of older patients treated with thyroid hormones report the concurrent use of medications that can interfere with the accuracy of thyroid function tests, potentially compromising treatment decisions, new research shows.

"We know from previous studies that thyroid hormone use is common in older adults and that there are a multitude of medications that can interfere with thyroid function tests in different ways," senior author Maria Papaleontiou, MD, told Medscape Medical News.

"However, to our knowledge, the extent of concurrent use of thyroid hormone and interfering medications in older adults, age 65 years and older, has not been previously explored," added Papaleontiou, of the Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor.

The findings were presented as a poster during virtual ENDO 2021, the Endocrine Society's annual meeting.

Commenting on the study, Thanh Duc Hoang, DO, an endocrinologist with the Walter Reed National Military Medical Center, in Bethesda, Maryland, said: "It is important for clinicians to be aware of various interactions and interferences of medications affecting the accuracy of thyroid function tests."

"If patients are not able to discontinue the medications shortly before the bloodwork, the clinicians may consider ordering different thyroid tests or assays that avoid the interferences," he told Medscape Medical News.

32% of Patients Taking Meds That Could Interfere With Tests

In evaluating data on 538,137 patients treated with thyroid hormones from the Corporate Data Warehouse of the Veterans Health Administration, spanning 2004-2017, first author Rachel Beeson, MD, and colleagues with the University of Michigan found most patients in the study were men (96.5%), White (77.1%), and had two or more comorbidities (62.6%).

Of this total, 170,261 (31.6%) patients treated with thyroid hormones, over a median follow-up of 56 months, were taking at least one drug that could potentially interfere with thyroid function tests

Among the drugs with potential thyroid test interference, about 28% of patients were taking prednisone or prednisolone, 8% were taking amiodarone, and 1.42% were taking phenytoin. Other reported drugs that could potentially interfere included carbamazepine (0.91%), phenobarbital (0.15%), lithium (0.40%), and tamoxifen (0.11%).

Multivariate analysis showed that characteristics associated with those most likely to have concurrent medication use included non-Whites (OR, 1.18 vs Whites), Hispanic ethnicity (OR 1.11 vs non-Hispanic), female sex (OR 1.12 vs males), and presence of comorbidities (eg, Charlson-Deyo comorbidity score ≥ 2, OR,  2.47 vs score of 0).

Meanwhile, older patients age 85 years and over had a lower likelihood of concurrent medications interfering with thyroid tests (OR, 0.47 vs age 65-74 years).

The findings are concerning given the wide use of levothyroxine to treat hypothyroidism, which is the most widely prescribed drug in the United States.

"Our findings not only highlight the complexity of thyroid hormone management in older adults in the context of polypharmacy and multimorbidity, but they also draw attention to vulnerable groups for this practice, which included female patients, non-Whites, patients of Hispanic ethnicity, and patients with comorbidities," Papaleontiou said.

Heparin, Biotin of Notable Concern

In a separate presentation during the ENDO meeting, Mark Gurnell, MBBS, PhD, of the University of Cambridge, Wellcome Trust, UK, described some commonly used agents that might interfere with thyroid function tests, including heparin and biotin.

"When you think about how much heparin is used in routine day-to-day clinical practice, this is an important potential problem to be aware of," Gurnell told Medscape Medical News.

The key issue with heparin is its ability to cause displacement of thyroid hormones from transport proteins, he explained. "This can be exacerbated if the sample is not processed quickly in the laboratory," he said. "It is certainly something that clinicians should be aware of, as it can occur with any form of heparin therapy."

Additionally, biotin has emerged as a concern, especially with its higher rates of use for nonmedicinal purposes.

"It is important to be aware if biotin is a potential problem for your local assays," Gurnell said. "Some platforms may be susceptible to interference in both free thyroid hormone and TSH measurements, and this can be very challenging because you may be faced with a biochemical picture of apparent elevated free thyroid hormones and suppressed TSH, which for all intents and purposes is a perfect mimic for classical primary hyperthyroidism."

Furthermore, if the TSH receptor antibody assay is triggered by biotin, you could wind up with what looks like autoimmune Graves' disease, he explained.

"My advice is to first determine which platforms your laboratory uses and what the likely vulnerabilities are," he noted. "If you work with assays that are not susceptible, then you probably don't need to worry about this, but if biotin could confound analyses, then you should think about asking patients about it."

"And you really do need to ask because, while some patients are taking biotin as a therapeutic, others may be taking it as a supplement and they likely won't mention it unless you directly ask the question."

Papaleontiou, too, explained that medications or supplements can interfere with thyroid function tests in a variety of ways, including decreasing the absorption of levothyroxine or affecting how well the pill dissolves.

And in contrast, "What is even more challenging is that some medications or supplements may appear to affect thyroid function based on lab tests when in reality they don't actually affect thyroid function and may lead to dose adjustments unnecessarily," she cautioned.

Recommendations to Counter Interference

Current recommendations to try to counter the effects of polypharmacy on thyroid treatment include advising patients to take thyroid hormones on an empty stomach at least 30-60 minutes prior to eating for optimal absorption.

If the patient is taking medications known to interfere with absorption of thyroid hormones, the recommendation is to space those out by at least 4 hours.

"The big challenge in older adults is that many of them do experience polypharmacy, being at risk for multiple drug-drug interactions," Papaleontiou said.

"Physicians and patients should be vigilant and communicate closely every time there is initiation of a new medication or supplement to consider whether there may be interference."

The authors have reported no relevant financial relationships. Hoang has reported being a speaker for Acella Pharmaceuticals.

ENDO 2021. Abstract P51-1. Presented March 20, 2021.

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