Management of Patients with Thyroid Nodules and Differentiated Thyroid Cancer: A summary

by Dr. David S. Cooper

Chair, American Thyroid Association Thyroid Nodule and Thyroid Cancer Guidelines Task Force

In november, the American Thyroid Association published a revision of its "Guidelines for the Management of Thyroid Nodules and Thyroid Cancer" in its journal, Thyroid. The guidelines are available free to the public at the American Thyroid Association web site (www.thyroid.org). The revised guidelines represent two years of work and modernize the original "thyroid nodule and thyroid cancer guidelines" that were published in 2006. The impetus for the revision was the large number of new clinical research findings that had been published on this topic over the last three years. Also, thyroid cancer is an important topic because of its increasing incidence in the United States and around the world. Furthermore, thyroid nodules, or “lumps on the thyroid,” continue to be diagnosed with great frequency, possibly because of the widespread use of various imaging procedures (CAT scans, MRIs, carotid ultrasound) that detect thyroid nodules "incidentally" or "by accident" with increasing frequency. The guidelines are "evidence-based" which means that the various research studies that were reviewed by the task force were rated according to whether the study provided "good" or "fair" evidence that a particular test or treatment would be effective. For those interventions where there is very little good research, the task force made recommendations based on “expert opinion.” Diagnosing Thyroid Cancer

For the management of thyroid nodules (See Dr. Duick’s piece and the thyroid nodules information), the guidelines focus on how physicians should evaluate patients with thyroid nodules using laboratory tests, thyroid ultrasound, and other imaging tools such as thyroid scans. It is recommended that all patients with one or more suspected thyroid nodules have thyroid ultrasound performed for three reasons: to precisely measure the nodule’s size; to see whether other nodules may be present within the thyroid that can't be felt; and, importantly, to look at the ultrasound appearance of the nodule or nodules, since it is now known that the ultrasound characteristics of a nodule is very helpful in establishing the likelihood it may be benign or malignant. The guidelines then make recommendations, based on the size of the nodule, the ultrasound appearance of the nodule, and other criteria, for which patients should have their nodule biopsied or aspirated, using a fine needle under ultrasound guidance. The guideline task force believes that the revised guidelines may lead to fewer biopsies being performed in the future, since the appearance of the nodule on ultrasound rather than its size should play a greater role in deciding whether a biopsy is performed.

Treating Thyroid Cancer

The extent of surgery that is necessary for patients with thyroid cancer is another major topic discussed in the revised guidelines. The guidelines review criteria to help decide which patients require a total thyroidectomy versus a simple lobectomy removing only half of the thyroid, and which patients should have removal of potentially involved lymph nodes in the neck near the thyroid at the time of surgery. Following surgery, many patients will receive radioactive iodine to destroy the small amount of thyroid tissue that was left behind, known as remnant thyroid tissue. The new guidelines review which patients should receive this form of therapy, and which patients can be followed without additional treatment. Recent studies suggest that radioactive iodine therapy is not necessary in many low risk patients, and the guidelines task force believes that the new recommendations will lead to fewer patients receiving radioactive iodine in the future.

The guidelines also discuss how patients with thyroid cancer should be treated with thyroid hormone following thyroidectomy. Many patients benefit from relatively high doses of thyroid hormone, which will lower their serum TSH levels. The purpose of this relates to the fact that TSH, a hormone that normally appears in the blood stream, can be a growth factor for thyroid cancer. On the other hand, too much thyroid hormone may have side effects, especially in elderly patients (e.g., osteoporosis in postmenopausal women, heart rhythm disturbances, symptoms of nervousness and anxiety). The guidelines discuss how to maximize the beneficial effects of thyroid hormone and to minimize the potential complications of thyroid hormone therapy.

Following Patients with Thyroid Cancer

The new guidelines review the use of serum thyroglobulin measurements in thyroid cancer patients. Thyroglobulin is a thyroid protein made by either normal thyroid tissue or thyroid cancer. Therefore, after all thyroid tissue is removed or destroyed by surgery and radioactive iodine therapy, serum thyroglobulin serves as an important tumor marker that is used to monitor patients to detect persistent or recurrent disease. The interpretation of thyroglobulin levels requires a certain degree of expertise on the part of the physician. The revised guidelines also discuss the management of patients with advanced thyroid cancer, and recommend that radioactive iodine therapy be used in some patients, while other patients may be suitable candidates for newer therapies that are still not yet approved for thyroid cancer management by the U.S. Food and Drug Administration (For more information, please see section by Steven Sherman). On the other hand, even patients with widespread disease may do well without any treatment at all, since thyroid cancer often progresses very slowly and may have few symptoms.

Future Thyroid Cancer Research

Finally, the guidelines present a number of areas for future research that the task force felt were especially important. These include more information on how to manage widespread metastatic disease using newer chemotherapy agents, better understanding of the long-term outcome of patients with very minimal disease that is detectable only because their serum thyroglobulin levels are slightly elevated, and better ways of measuring serum thyroglobulin in patients who have anti-thyroglobulin antibodies. This last issue is a particularly vexing one for approximately 20% of thyroid cancer patients, in whom serum thyroglobulin cannot be measured accurately.

The revised "thyroid nodule and thyroid cancer guidelines" is a "living document", and will be revised again in another 2-3 years. The field is moving rapidly, and the American Thyroid Association is dedicated to providing clinicians with the best and most up to date evidence to help them manage their patients who have thyroid nodules and thyroid cancer.

David S. Cooper, MD, is a graduate of Johns Hopkins University. He received his medical degree from Tufts University School of Medicine where he was elected to Alpha Omega Alpha, and completed his Internal Medicine residency at Barnes Hospital/Washington University School of Medicine. He completed his Endocrinology Fellowship training at the Massachusetts General Hospital/Harvard Medical School. He is Professor of Medicine and International Health at the Johns Hopkins University School of Medicine and the Bloomberg Johns Hopkins School of Public Health, and Director of the Johns Hopkins Thyroid Clinic. He is a Contributing Editor of the Journal of the American Medical Association (JAMA), and is the Deputy Editor of the Journal of Clinical Endocrinology and Metabolism. He also serves as Editor-in-Chief for Endocrinology at Up-to-Date. He is the current Chair of the Subspecialty Board for Endocrinology, Diabetes, and Metabolism of the American Board of Internal Medicine. Dr. Cooper is the past Treasurer and the past President of the American Thyroid Association, and is also the recipient of the American Thyroid Association’s Distinguished Service Award.