Highlights From the 76th Annual Meeting of the American Thyroid Association

Kenneth D. Burman, MD

Disclosures

January 05, 2005

In This Article

Advances in Thyroid Cancer Treatment

The cornerstones of therapy for differentiated thyroid cancer (ie, papillary or follicular) include total thyroidectomy followed by 131-I remnant ablation. Patients are then given thyroid hormone suppression therapy and monitored by periodic neck examinations, serum thyroid function tests and thyroglobulin levels, and radiologic studies of the neck. Follow-up radioiodine scans are also performed periodically. Following thyroidectomy, elevations in serum TSH are required to perform a radioiodine scan and then also to treat the patient with radioiodine. TSH elevations can be achieved by withdrawal of thyroid hormone therapy or by injections of recombinant human TSH. Withdrawal of thyroid hormones is the standard, time-honored method but it causes hypothyroidism, whereas recombinant human TSH injections can be performed while a patient continues thyroid medication, thus avoiding the possible adverse effects of hypothyroidism.

In addition to making it possible to perform an isotope scan, recombinant human TSH injections (and withdrawal scans as well) stimulate residual thyroid cells to secrete thyroglobulin, which can be measured and helps assess the presence of residual thyroid cancer. Thyroid hormone withdrawal has been utilized for many years, but it does have the associated adverse effect of causing hypothyroidism with its attendant signs and symptoms. Many studies are being performed to assess whether the ability to detect residual thyroid tissue by using recombinant human TSH is comparable to the thyroid hormone withdrawal method.

During the American Thyroid Association Symposium "Recent Advances in the Treatment of Thyroid Cancer,"[1] Furio Pacini, MD, University of Pisa, Italy, reviewed important new information about the use of recombinant human TSH for thyroid remnant ablation in patients with differentiated thyroid cancer. This use of recombinant human TSH is not simply for diagnostic purposes; Dr. Pisa's group is extending its application to 131-I treatment.

Remnant ablation refers to the initial radioiodine scan and treatment following thyroidectomy, when it is expected that there will be uptake (albeit minimal) by residual thyroid tissue, the majority of which is expected to be benign. Currently, recombinant human TSH is approved by the US Food and Drug Administration (FDA) for use in radioiodine scans but not for treatment purposes. The use of recombinant human TSH stimulation to perform thyroid scans (and treatment) is theoretically preferable to the alternative, time-honored option of rendering patients hypothyroid for this purpose, because hypothyroidism may be associated with symptoms. The question that remains is whether the results of administering radioiodine under the influence of recombinant human TSH stimulation are equivalent to those of giving radioiodine while a patient is hypothyroid.

Dr. Pacini presented information from an international, randomized, controlled trial comparing the use of recombinant human TSH with thyroid hormone withdrawal as preparation for thyroid gland remnant ablation in differentiated thyroid cancer. All patients were treated with 100 mCi (3.7 GBq) of 131-I. Sixty-three eligible patients were randomized to participate, and 60 completed the study; 28 in the hypothyroid group and 32 in the euthyroid (recombinant human TSH) group. When studied about 8 months after 131-I therapy, the results indicated that there were no significant differences in the 2 groups with regard to thyroid remnant ablation, whether defined as no visible uptake or less than 0.1% uptake or by finding a serum thyroglobulin level less than 1 ng/mL 8 months after treatment. In fact, over 98% of patients in each group had ablation of thyroid tissue as determined by isotope scan, and about 85% of patients in each group had a stimulated thyroglobulin level less than 1 ng/mL. Dr. Pacini concluded that radioiodine effectiveness was comparable using either method of recombinant human TSH stimulation or thyroid hormone withdrawal and that quality of life was better preserved with the use of recombinant human TSH and avoidance of hypothyroidism after thyroid hormone withdrawal.

This study was well conducted and gives us important new information. However, additional studies need to be performed, and it should be noted that the FDA has not yet approved the use of recombinant human TSH stimulation for treatment purposes with radioiodine.

Professor Martin Schlumberger, Institute Gustave-Roussy, Villejuif, France, analyzed various methods of following patients with differentiated thyroid cancer who had previously received a total thyroidectomy and 131-I therapy. Possible methods of monitoring include any combination of radioiodine scans, baseline or stimulated thyroglobulin levels, and radiologic studies such as neck sonogram and MRI. Different institutions have varying practices. In Professor Schlumberger's analysis, periodic 131-I scans had the poorest ability to detect neck recurrences, with sensitivity ranging from 21% and 45%. Neck sonograms had a sensitivity of 70% to 100%, and recombinant human TSH stimulation with thyroglobulin determinations had a sensitivity of 57% to 82%.

Dr. Schlumberger also reported results from a French multicenter study that analyzed the outcome and sensitivity of different methods of following low-risk patients who did not have evidence of residual disease after their initial radioiodine therapy. One hundred twenty-six of 968 patients had a detectable serum thyroglobulin (assay sensitivity 0.7 ng/mL); of these, only 32 had evidence of disease by other studies. It seems that the stimulated serum thyroglobulin level (during thyroid hormone withdrawal or with recombinant human TSH stimulation) was an excellent indicator of recurrent disease. It appears that if the stimulated thyroglobulin level is less than 1 ng/mL, the likelihood of a recurrence is less than 1% over about 10 years. If the stimulated serum thyroglobulin level is greater than 1 ng/mL, 6 of 26 patients had a recurrence by the sixth year of follow-up. As a result of this information, Dr. Schlumberger suggests a monitoring method for low-risk patients that stresses the utility of neck sonograms and recombinant human TSH-stimulated thyroglobulin levels. It is emphasized that this algorithm applies only to low-risk patients.

Stephanie Lee, MD, PhD, Boston University Medical Center, Massachusetts, reviewed the possible complications of radioiodine therapy. This form of therapy is generally safe, but potential complications include sialoadenitis with swelling and/or tenderness, taste distortion, and, rarely, xerostomia. These complications cannot be completely prevented, but the use of sialogogues, such as sour candies, and parotid massage given for several days following radioiodine therapy may be beneficial. Usually these complications are transient. Nausea and vomiting can occur but can be decreased with the prophylactic use of antiemetics. Neck discomfort related to the uptake of radioiodine by remnant thyroid tissue may also occur. Although it has not been well studied, testicular and gonadal function seems to be normal, especially when studied 6 to 12 months following radioactive iodine. The most serious potential adverse effects are pulmonary fibrosis, bone marrow suppression, and anaplastic transformation of a previously well-differentiated tumor. Pulmonary fibrosis may occur, most notably when there is widespread metastatic tumor in the lung with resultant trapping of isotope in the pulmonary tissue and resultant radiation exposure.

Leeper proposed in 1980 that a limit of less than 80 mCi 131-I retained at 48 hours in the presence of pulmonary tumor and less than 120 mCi 131-I retained without pulmonary metastases would decrease the risk of radiation fibrosis.[2] His subsequent 20-year experience seems to have confirmed this hypothesis. If the total-body exposure is limited to less than 200 cGy (rad) following 131-I exposure, the likelihood of bone marrow suppression is very low. It is controversial whether radioactive iodine causes leukemia to develop. It seems that this event, if it occurs, is extremely unusual and is limited mainly to patients who have received a cumulative 131-I dose of greater than 1000 mCi. Bone, colon, bladder, and salivary tumors have been discussed in relation to 131-I therapy administration, but there is no consensus that they occur in increased frequency, and further studies in this area are required.

In summary, radioactive iodine therapy is considered safe and effective for the treatment of patients with differentiated thyroid cancer. We tend to treat all patients with follicular cancer with 131-I, and also all patients with papillary thyroid cancer greater than 1 cm in maximum diameter. There are many variations to this approach, especially when a papillary thyroid cancer is small (less than 1 cm) but multifocal. We believe it is important for the patient to be an integral part of the entire coordinated multidisciplinary healthcare team, and that the patient should be as knowledgeable as possible about this process. Further, it seems prudent to have the patient use sialogogues such as lemon candy frequently for several days following 131-I therapy. The routine use of antiemetics and laxatives and the maintenance of adequate hydration also seem reasonable to try to decrease the gastrointestinal tract and bladder exposure to 131-I to the greatest extent possible.

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