What Is The Thyrogen Stimulation Test?

Last Editorial Review: 1/11/2018

Ask the experts

I was diagnosed with a follicular variant of papillary thyroid cancer (malignant). Treatment thus far has included total thyroidectomy and radioiodine treatment. I had been on Synthroid for 14 years prior to the diagnoses of the cancer. I am diabetic and am having a terrible time with elevated serum creatinine when they wean me off the Synthroid (using Cytomel) for cancer scans. It really seems to make daily difficulties in my health management seem exponential. I heard there is a recombinant TSH injection being studied. When will it be available? How does is work? What properties make it able to be continued in prep for future cancer scans?

Doctor's response

Thyroid cancer affects approximately 19,000 people in the United Sates annually. The cure rate is very high, but the risk for post treatment recurrence is a life long reality. In fact the recurrence rate may be up to 25%. The key to successful management is to monitor patients regularly. Iodine whole body scanning, along with measurement of thyroglobulin levels (a protein made solely by thyroid tissue) are standard methods of follow-up on thyroid cancer.

Since Iodine is absorbed by the thyroid gland and by certain thyroid cancer tissue, radio-actively labeled iodine (radioiodine) can be used to detect thyroid cancer recurrence or spread to other organs (metastasis). When the radio-active iodine is injected into a vein, the radio-activity is picked up by thyroid tissue and by certain thyroid cancer tissue. A nuclear camera can be used to detect areas with concentration of radio-activity.

In patients on Synthroid (or any other brand name of synthetic T4 hormone replacement), the radioiodine scan cannot be performed until after stopping replacement for 4-6 weeks. This is because synthetic thyroid hormone replacement suppresses the thyroid tissue's ability to pick up iodine. The concern then becomes having a falsely negative test result.

Stopping T4 therapy for weeks can, in fact, complicate glucose control in patients with diabetes mellitus. In addition, patients often feel "low" or " hypothyroid." Constipation, fatigue, bloating, cold intolerance and metabolic abnormalities associated with under-replacement of thyroid hormone are seen. Some patients find these 6 weeks of hormone withdrawal extremely difficult to tolerate. In fact, that's actually part of the point: to render the patient hypothyroid so the thyroid tissue is really " thirsty" for iodine. As a result, the likelihood of picking up any thyroid tissue on the scan is increased.

Recombinant TSH (thyrotropin alfa) was approved by the U.S. Food and Drug Administration in 1998 for use as a tool in monitoring patients who have been treated for well-differentiated thyroid cancers. Recombinant TSH is a synthetic form of thyroid stimulating hormone, and it does just that- stimulates the thyroid tissue. Recombinant TSH is indicated for use as an adjunctive diagnostic tool for serum thyroglobulin testing with or without whole body iodine scanning. It is given in the form of an intramuscular injection.

Since the goal of scanning patients and monitoring thyroglobulin levels in the post thyroid cancer state is to detect new, abnormal tissue, stimulating the thyroid tissue with recombinant TSH for a short period should theoretically provide a higher yield of true positives. In one study, compared with thyroid hormone withdrawal alone, the use of recombinant TSH had a sensitivity shown to be 90% overall, with a 100% in identifying disease outside of the thyroid gland area in earlier studies. This means that some cancers in the thyroid bed actually went undetected. In another study, metastatic disease was missed in 9 out of 38 patients. A recent retrospective study by Robbins et al (2001) compared the use of recombinant TSH with thyroid hormone withdrawal as preparation for iodine scanning and thyroglobulin testing in monitoring patients post cancer treatment for disease recurrence. In this analysis, patients choose either recombinant TSH or thyroid hormone withdrawal. No differences were found between groups (each of which numbered over 100 patients) in diagnostic accuracy.

As you can see by the variance in the literature, recombinant TSH does not carry a 100% guarantee of finding cancer recurrences. The gold standard is still thyroid hormone withdrawal for 4-6 weeks then thyroglobulin testing and iodine scanning. In patients not willing to stay off thyroid hormone replacement for 6 weeks, or in those in whom being off for that length of time is contraindicated for medical reasons, it may be an agreeable option. Recombinant TSH is administered at a dose of 0.9mg intramuscularly every 24 hours for 2 doses or every 72 hours for 3 doses.

Recombinant TSH has been generally well tolerated. Approximately 15% of patients experience mild reactions such as headache or nausea. Infrequently, administration of this stimulating substance has resulted in rapid expansion of lesions. This is especially important in metastatic disease in the spine, where growth could cause nerve compression, or in the neck where tracheal compression could occur. These events are exceedingly rare, but patients should be made aware of the risks. Pre-treatment with steroids may help to prevent these events.

Another alternative for patients who do not like being withdrawn from T4 replacement for over a month, is the option of using liothyronine sodium (Cytomel). Cytomel is a synthetic form of T3 (see thyroid replacement article) and the time that it functions in the body is much shorter than T4. As a result, a patient switched for T4 to T3 a month or so before iodine scanning/thyroglobulin measurements, and can be maintained on T3 replacement for up to 2 weeks before the procedures. This significantly shortens the time the patient is rendered off replacement.

All these methods are options for patients to discuss with their physicians. Many physicians have specific practice preferences, and a through discussion will help the patient and physician plan the ideal approach.

Medical Author: Ruchi Mathur, M.D.