Heterophile Antibodies Can Cause False Thyroid Test Results

Heterophile antibodies can cause falsely elevated TSH levels in some patients. Istockphoto

In a study presented at the 81st annual meeting of the American Thyroid Association (ATA) in 2011, researchers reported that interference from heterophile antibodies can pose a risk of erroneous results on the Thyroid Stimulating Hormone (TSH) test. The TSH test is considered by mainstream endocrinology to be the so-called "gold standard" test for evaluating thyroid function.

It's believed that heterophile antibodies -- also known as human antianimal antibodies -- are developed after exposure to animal-derived pharmaceuticals and antibody therapies.

That means that these heterophile antibodies are more common if you have received blood transfusions or vaccinations, or you have been exposed to certain animals -- but not household pets.

According to Nikola A. Baumann, PhD, director of clinical chemistry at the Mayo Clinic in Rochester, Minnesota, it's estimated that the prevalence of people with heterophile antibodies ranges from one percent to 80 percent of the population.

According to Dr. Baumann, the antibodies can interfere with the test to cause false-positive or false-negative results. In a Medscape meeting summary, she said, "The wide discrepancy is related to how the antibody is identified."

Dr. Baumann said that Mayo's Endocrinology Clinic receives some 30 requests per year from clinicians suspecting heterophile antibody interference on TSH tests, and that interference was confirmed in a third of the samples. But in 2010, there was a marked increase in the prevalence of antibody interference.

"In the latter half of 2010, something changed," Dr. Baumann said. "We noticed a significant increase, not only in physician requests for investigations; the number of positive-confirmed heterophile antibody interferences tripled."

Dr. Baumann and her colleagues found that 4.4 percent of the hundreds of samples she tested were affected by heterophile antibodies.

Despite TSH test results that came back at 10.0 or higher -- typically indicative of hypothyroidism -- the accurate TSH levels were below 0.10 mIU/L in 18% of the patients; between 0.3 and 5.0 mIU/L in 53% of the patients, and between 5.0 and 10.0 in 29% of the patients.

Dr. Baumann emphasized that although an abnormal TSH result should lead to further testing, it doesn't always, so the interference can have serious implications.

According to Dr. Baumann:

"The clinical impact of this change has the potential to be severe because TSH is, for better or worse, often the primary test of thyroid function, and treatment decisions are made based on this. It definitely highlights the importance of communication between laboratories and the importance of follow-up testing."

The ATA session where this research was presented was moderated by Francesco Celi, MD, an endocrinologist at the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health in Bethesda, Maryland. Dr. Celi acknowledged that the heterophile antibody interference, although uncommon, is one that doctors need to be on the lookout for when ordering tests of their patients' thyroid levels.

A red flag for clinicians, he pointed out, is when the tests come back with discrepancies.

In his presentation, Dr. Celi said:

"The hallmark of this condition is a discrepancy between TSH value and free T4 value, and most important between laboratory values and patient's conditions. Endocrinologists, in particular, should be on alert for this."

What This Means for Patients

These findings are clinically significant, because if you are being treated for hypothyroidism, and you have a TSH test result that comes back elevated, it's likely that your physician would increase your dose of thyroid hormone replacement.

If your elevated TSH levels are, however, due to the heterophile antibodies, this dosage increase could cause overdosage and medication-induced hyperthyroidism.

If you are feeling well on your replacement dosage, and you have a high TSH test result like this, you should ask your physician to also run Free T4 and Free T3 tests, to double-check whether they correlate to the elevated TSH level.

If you are not yet diagnosed with a thyroid condition, and have a TSH test that comes back elevated, you should also ask your physician to run Free T4 and Free T3 tests to confirm the hypothyroidism. Otherwise, hypothyroidism could be erroneously diagnosed, and treatment started -- based on the elevated TSH test -- even if you are not clinically hypothyroid. This then puts you at risk of developing medication-induced hyperthyroidism.


Melville, Nancy, "Antibody Interference Can Taint TSH Assays," Nov 03, 2011 Medscape , Online.

Krishnan, S. et. al. "Falsely raised TSH levels due to human anti-mouse antibody interfering with thyrotropin assay," Postgraduate Medical Journal , 2006 November; 82(973): Online

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