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December 1, 1998

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New Monitoring Technique Checks Thyroid Cancer Without Misery

The good news about thyroid cancer is that treatment for it is relatively easy. Surgeons remove the thyroid gland and follow with a dose of radioactive iodine designed to destroy lingering cells. The bad news is that sometimes not all the cells are caught and the subsequent yearly monitoring that must follow causes patient anxiety and physical illness. Current monitoring methods also carry a slight risk of accelerating tumor growth.

Now a study at Johns Hopkins suggests a new way to safely and effectively detect left-over thyroid cells.

The test relies on the researchers' discovery that stray human thyroid cells can circulate in the bloodstream. It also extends the use of PCR (polymerase chain reaction) from a technique important in gene discovery and cancer diagnosis to one for patient monitoring -- a use "that will likely become standard in the near future," says endocrinologist Michael Levine, M.D., who led the research team. The study was published in this month's Journal of Clinical Endocrinology and Metabolism.

Historically, physicians look for remaining thyroid cells either by having patients take radioactive iodine, which concentrates in the thyroid gland and can be detected by scanners; or by analyzing blood for thyroglobulin, a protein made by thyroid cells. The more thyroglobulin in the bloodstream, the reasoning goes, the more thyroid cells. Physicians need both methods to pick up leftover thyroid cells that could be cancerous.

But because both tests deliver false results if patients' blood contains thyroid hormone, those under treatment and scheduled for monitoring must stop taking the thyroid hormone pills they've used daily since their thyroid gland removal. The resulting low levels of the hormone, says Levine, "quickly bring on the symptoms of hypothyroidism: People are easily tired and often depressed, their skin becomes dry, they get forgetful, their heart rate decreases, they can't tolerate cold and they become generally miserable for two to three weeks."

With the new test, patients can stay on their thyroid medicine. Based on the presence of genes for thyroglobulin, rather than on thyroglobulin itself, the test uses PCR to amplify very low level gene activity -- the sort you'd find with stray cells -- to the point where it can be detected. "The technique is extremely sensitive. It can tell, indirectly, if just one or two thyroid cells exist in a teaspoonful of blood," says Levine.

"What makes the test workable is that it needs only patients' blood. We didn't realize until now that everyone's blood contains circulating thyroid cells."

The test additionally avoids a rise in another hormone, thyroid stimulating hormone, which may encourage the growth of malignant thyroid cells. Some risk of this exists with present tests.

With an eye to widespread clinical use of the test, the research team is now clarifying whether stray cells are malignant or benign. They're also quantifying test results. "We should be able to follow levels of thyroglobulin gene activity in cancer patients -- the way you can follow HIV levels in AIDS patients -- to see how people respond to treatment. Ultimately," says Levine, "we hope assays like this will avoid the need to stop taking thyroid hormone and make monitoring faster, easier and more sensitive."

A similar assay using PCR to monitor prostate cancer treatment is being tested elsewhere.

Other researchers on the project were Matthew D. Ringel, M.D., and Paul W. Ladenson, M.D., both of Johns Hopkins. Funding for the project was from a United States Public Health Service grant and by Johns Hopkins.


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