July 29, 2007 Researchers at Georgetown University Medical Center have developed a fast and accurate way to measure a major hormone released by the thyroid gland -- an advance they say may help in the treatment of many women who have overactive or underactive thyroid glands.
According to the American Association of Clinical Endocrinologists, approximately 27 million Americans have thyroid glands that produce too little of the hormone, thyroxine, a condition known as hypothyroidism, or else the gland produces too much, known as hyperthyroidism. Thyroxine regulates the body’s metabolism, and hypothyroidism, associated with fatigue and weight gain, is much more common than hyperthyroidism, characterized by weight loss. More than eight out of 10 patients with thyroid disease are women, and nearly one out of 50 women in the United States is diagnosed with hypothyroidism during pregnancy.
In order to treat these conditions, physicians need to know how much synthetic thyroxine to either give patients or how much natural hormone should be blocked, and there have long been concerns that the common “immunoassay” test now in use worldwide is neither specific nor very accurate. To date, the immunoassay test has been used to measure those levels in women known to have abnormal levels of thyroid function based on a screening test.
In this study, published in the April issue of the journal Thyroid, the researchers tested the method they had developed and found that it was far superior to the immunoassay, and just as good as a very expensive, time-consuming, but very accurate laboratory analysis that is less commonly used.
“This is a very specific test and is not plagued by the false readings that make the currently used immunoassay test notoriously inaccurate,” said one of the study’s investigators, Jacqueline Jonklaas, M.D., Ph.D., assistant professor in the Department of Medicine. “After further confirming studies, we believe this new assay will become the test of choice in most clinical situations.”
The test to measure thyroid hormones, which uses tandem mass spectrometry, was developed by Steven Soldin, Ph.D. FACB, a professor at Georgetown University Medical Center in the Departments of Medicine, Pharmacology and Oncology and Director of both the Georgetown Bioanalytical Core Laboratory and Children’s National Medical Center Chemistry Laboratory. Soldin came to GUMC in 2002 to design such state-of-the-art tests, and now, versions of the same tandem mass spectrometry technology that can measure free thyroxine (FT4) levels in blood are already in use at a number of medical centers, says Dr. Soldin, a co-author.
In this study, researchers tested the ability of their new test to measure thyroxine in blood by enrolling 98 pregnant women as well as 29 women who were not pregnant. Measuring the hormone in pregnant women can be tricky, the researchers say, because some conditions that may be present (high levels of binding proteins and certain antibodies) can affect immunoassay performance.
Thyroxine output dramatically changes during pregnancy in order to support development of the fetus. Thyroxine helps control metabolism and physical development, and because a fetus does not develop its own supply until the second trimester, it is crucial that pregnant women have adequate supplies in the first trimester, investigators say.
The investigators used three different tests -- immunoassay, the Georgetown tandem mass spectrometry, and the “gold standard” laboratory test known as equilibrium dialysis -- to measure the hormone in blood samples donated by the volunteers. They found that, across all stages of pregnancy, there was almost total agreement between mass spectrometry and equilibrium dialysis, but immunoassay results differed significantly.
“Pregnancy is the most difficult situation in which to measure thyroxine, and if this test can perform so well in these conditions, it can likely be used for all other clinical needs,” Jonklaas said.
One major use of such a test would be to help guide treatment of people with hypothyroidism or hyperthyroidism, Jonklaas said. Physicians diagnose these conditions using a test that measures thyroid-stimulating hormone (TSH), a hormone released by the pituitary gland which stimulates the thyroid gland to secrete thyroxine. When TSH is high, levels of thyroxine are low, and vice versa.
But after the condition is diagnosed, doctors have used the immunoassay to determine what level of thyroxine should be supplemented or repressed. “We think our treatment of hyperthyroidism and hypothyroidism would be much more accurate if we combined TSH testing with tandem mass spectrometry instead of with the immunoassay,” Jonklaas said.
The reason the mass spectrometry test is so accurate is because it measures the thyroxine molecule specifically and uses a filtering system to separate out the “free” thyroxine --the form that is active--from deactivated thyroxine that is bound to proteins, Soldin said. The direct/analogue immunoassay test, on the other hand, doesn’t separate the two forms, but uses a mathematical formula to come up with a result, he said. “It is so cheap and quick to use, but it provides a number that can be wrong almost half the time.”
The study was funded by the National Center for Research Resources, the National Institutes of Health, and by the Office of Research on Women’s Health. Dr. Soldin is the inventor of the described technology for which Georgetown University has filed a patent application. Dr. Soldin is also partially supported by a grant from Applied Biosystems, to which the technology has been licensed for commercial development. He is neither a paid consultant nor an owner of the company.
The first author of the study is assistant professor Natasa Kahric-Janicic, M.D., PhD., assistant professor of medicine, and other authors include associate professor Offie Soldin, Ph.D.,M.BA, associate professor of oncology, Threvia West, M.D., and Jianghong Gu, Ph.D.
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