Click here for Frequently Asked Questions on Recombinant TSH.
Recombinant Thyroid Stimulating Hormone (TSH), known by the trade name of Thyrogen, produced by genetic engineering in bacteria and a product of Genzyme Therapeutics, has been administered, in controlled clinical trials, to patients with thyroid cancer requiring diagnostic radioactive iodine scans and thyroglobulin determinations. In the majority of cases, recombinant TSH produces acceptable iodine uptake comparable to that observed following withdrawal of thyroid hormone and stimulation of iodine uptake by endogenous pituitary TSH.
The advantage of recombinant TSH is the elimination of the need to stop thyroid hormone to make patients hypothyroid in order to carry out the diagnostic scan. Since withdrawal and subsequent restarting of thyroid hormone can be mildly to moderately unpleasant, and may be associated with hypothyroid symptoms for 4-8 weeks, use of recombinant TSH can improve quality of life for these patients who can remain on their normal levels of thyroid hormone at the same time as they receive recombinant
TSH as studied in Cost-effectiveness
of using recombinant human TSH prior to radioiodine ablation for thyroid
cancer, compared with treating patients in a hypothyroid state: the German
J Endocrinol. 2006 Sep;155(3):405-14. For an overview of recombinant TSH, see Recombinant human thyroid-stimulating hormone: pharmacology, clinical applications and potential uses. BioDrugs. 2003;17(1):19-38.
A number of studies have demonstrated that quality of life may deteriorate
in patients withdrawn from thyroid hormone, relative to patients using
recombinant TSG as illustrated in A
Comparison of Short-term Changes in Health-related Quality of Life in
Thyroid Carcinoma Patients Undergoing Diagnostic Evaluation with rhTSH
Compared to Thyroid Hormone Withdrawal. J
Clin Endocrinol Metab. 2006 Jan 4; [Epub ahead of print]
A large study of over 200 patients with thyroid cancer compared the results of scan sensitivity and accuracy in patients receiving recombinant TSH, followed by thyroid hormone withdrawal. There were no major differences in scan sensitivity using the two different modalities, although thyroid hormone withdrawal was slightly better. Hence recombinant TSH is a reasonable alternative to thyroid hormone withdrawal for diagnostic scans in patients with thyroid cancer. For more information on these studies, see J Clin Endocrinol Metab 1999 Nov;84(11):3877-85 A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. For a review of the rationale underlying the use of Thyrogen, see Recombinant human thyrotropin in the management of thyroid cancer. Curr Opin Oncol 2001 Jan;13(1):39-43. To review an independent comparison of the sensitivity of thyroglobulin testing and whole body scanning for thyroxine withdrawal versus Thyrogen in 72 Italian patients with thyroid cancer, see Prediction of Disease Status by Recombinant Human TSH-Stimulated Serum Tg in the Postsurgical Follow-Up of Differentiated Thyroid Carcinoma. J Clin Endocrinol Metab. 2001 Dec 1;86(12):5686-5690. To review a larger series from Italy describing Thyrogen use, see The use of recombinant human TSH in the follow-up of differentiated thyroid cancer: experience from a large patient cohort in a single centre. Clin Endocrinol (Oxf). 2002 Feb;56(2):247-52.
Although there is less information on high risk patients treated with radioactive iodine using recombinant TSH in prospective studies, retrospective analyses do not appear to show significant differences in outcome in higher risk thyrid cancer patients administered radioactive iodine using withdrawal vs. recombinant TSH Recombinant human thyroid stimulating hormone-assisted radioactive iodine remnant ablation in thyroid cancer patients at intermediate to high risk of recurrence
It appears that while both the scan and the thyroglobulin blood test are both important components of the Recombinant TSH testing protocol, the thyroglobulin blood test is a more sensitive indicator of thyroid remnants or disease recurrence. See Clinical comparison of whole-body radioiodine scan and serum thyroglobulin after stimulation with recombinant human thyrotropin. Thyroid. 2002 Jan;12(1):37-43.
Indeed, some studies have shown that the sensitivity of the total body scan for picking up residual thyroid cancer after the initial radioactive treatment is extremely low, whereas ultrasound may be a better choice, as shown in Serum thyroglobulin and I whole body scan after recombinant human TSH stimulation in the follow-up of low-risk patients with differentiated thyroid cancer. Eur J Endocrinol. 2003 Jan;148(1):19-24.
Although there is less information about the use of recombinant TSH in children or teenagers, there do not appear to be significant differences in the kinetics of the TSH rise following recombinant TSH administration in this age group. See SERUM TSH LEVELS FOLLOWING RECOMBINANT HUMAN TSH INJECTIONS IN CHILDREN AND TEENAGERS WITH PAPILLARY THYROID CANCER. J Clin Endocrinol Metab. 2005 Sep 20; [Epub ahead of print].
There is limited information on long term follow up of "low risk" patients who received Thyrogen, vs. withdrawal from thyroid hormone, for thyroid remnant ablation and radioactive iodine therapy. Analysis, after a follow up period of ~3.7 years, of 48 patients who received Thyrogen or withdrawal, demonstrated that of 43 patients studied with both a scan and thyroglobulin testing, all 43 patients demonstrated continued evidence for successful ablation and lack of a thyroid remnant. Hence there continues to be no evidence, in this small group of patients, for any difference in efficacy for Thyrogen vs. withdrawal in regard to efficacy of remnant ablation. See Follow-up of low-risk differentiated thyroid cancer patients who underwent radioiodine ablation of postsurgical thyroid remnants after either recombinant human thyrotropin or thyroid hormone withdrawal. J Clin Endocrinol Metab. 2009 Nov;94(11):4171-9. Epub 2009 Oct 22. Nevertheless, there remains some uncertainty about the precise length of time required for withdrawal from thyroid hormone (generally 3-4 weeks), as well as the optimal TSH elevation (usually at least 30 or greater) required for maximal sensitivity for detection of increases in thyroglobulin, as outlined in In Thyroidectomized Patients with Thyroid Cancer, a Serum TSH of 30 µU/ml after Thyroxine Withdrawal is not always Adequate for Detecting an Elevated Stimulated Serum Thyroglobulin Thyroid. 2012 Sep 14
Download a brief summary sheet of Instructions for Thyrogen testing. To arrange either Thyrogen or Withdrawal testing with a Thyroglobulin blood test and a total body scan, download Testing Information, complete the form and Fax to Dr. Drucker's office.
Thyrogen is supplied as a lyophilized powder in a vial that contains 1.1 mg of recombinant TSH, mannitol, sodium phosphate, and sodium chloride. The following information is taken directly from the Genzyme Thyrogen Web site.
Administration and Dosage
After reconstitution with 1.2 mL Sterile Water for Injection, USP, 1.0 mL solution (0.9 mg thyrotropin alfa) is administered by intramuscular (IM) injection to the buttock. THYROGEN 0.9 mg IM may be administered every 24 hours for two doses or every 72 hours for three doses.
Thyroglobulin Testing Protocol
For serum thyroglobulin testing, the serum sample should be obtained 72 hours after the final injection of THYROGEN.
Whole Body Scanning (WBS) Protocol
For radioiodine imaging, radioiodine administration should be given 24 hours following the final THYROGEN injection. Scanning should be performed at 48 hours following radioiodine administration (72 hours after the final injection of THYROGEN).
The following parameters were utilized in the second phase III study for scanning with THYROGEN:
- A diagnostic activity of at least 4 mCi (148 MBq) 131I
- The use of THYROGEN allows for radioiodine imaging while patients are on T3 and/or T4. Data on radioiodine 131I kinetics indicate that the clearance of radioiodine is approximately 50 percent greater while euthyroid/hyperthyroid than during the hypothyroid state when renal function is decreased, resulting in less radioiodine retention in the body at the time of imaging. This should be considered when selecting the activity of radioiodine for use in radioiodine imaging
- Whole body images should be acquired for a minimum of 30 minutes and/or until a minimum of 140,000 counts is obtained. Scanning times for single (spot) images of body regions should be 10 to 15 minutes or less if the minimum number of counts is reached sooner (i.e. 60,000 counts if using a large field-of-view camera or 35,000 counts if using a small field-of-view camera)
Instructions for use:
THYROGEN® (thyrotropin alfa for injection) is for intramuscular (IM) injection to the buttock. The powder should be reconstituted immediately prior to use with 1.2 mL of the diluent provided. Each vial of THYROGEN and each vial of diluent (Sterile Water for Injection) is intended for a single use; discard any unused portion of diluent.
THYROGEN should be stored at 2°C to 8°C (36°F to 46°F). Just prior to injection, THYROGEN may be allowed to reach room temperature.
If necessary, the reconstituted THYROGEN solution can be stored for up to 24 hours at a temperature between 2°C and 8°C, while avoiding microbial contamination.
DO NOT USE THYROGEN AFTER THE EXPIRATION DATE ON THE VIAL.
Protect from light.
Safety and Tolerability
The most common adverse events reported in clinical trials with THYROGEN® (thyrotropin alfa for injection) were nausea (11 percent), headache (7 percent), asthenia (3 percent), and vomiting (2 percent). Mild reactions of hypersensitivity consisting of urticaria (<1 percent) and rash (<1 percent) have also been reported. In clinical trials, no patients have developed antibodies to thyrotropin alfa after either single or (in 27 cases) repeated use of the product.
Seven percent of patients in a special treatment protocol for treatment of patients with advanced cancer who had a high risk of brain metastases experienced acute hemiplegia, hemiparesis, or pain 1 to 3 days after THYROGEN administration. Pretreatment with corticosteroids may be considered in this setting. THYROGEN is known to cause a transient but significant rise in serum thyroid hormone concentration. Therefore, caution should be exercised in patients with a known history of heart disease and with significant residual thyroid tissue.
Recombinant TSH has not been approved in Canada for administering therapeutic doses of radioactive iodine for the treatment of thyroid cancer or for ablation of thyroid tissues, although these treatment modalities are currently undergoing examination in several clinical trials.
At present, withdrawal of thyroid hormone, which then results in the stimulation of endogenous pituitary TSH release is the only recommended procedure for therapeutic treatment with radioactive iodine for patients with thyroid cancer. For patients having a scan after withdrawal of thyroid hormone, it is also important to obtain a thyroglobulin blood test at the same time of the scan. As the results of the thyroglobulin test can take several days to a week to come back, it is advisable to stay off thyroid hormone completely or start back on T3 (Cytomel) while waiting for the results of the thyroglobulin, depending on your physicians recommendation.
Nevertheless, the results of clinical studies demonstrate that recombinant
TSH is safe and effective as an adjunct to ablate thyroid remnants in
patients with thyroid cancer as shown in Radioiodine Ablation
of Thyroid Remnants after Preparation with Recombinant Human Thyrotropin
in Differentiated Thyroid Carcinoma: Results of an International,
Randomized, Controlled Study. J
Clin Endocrinol Metab. 2005 Dec 29; [Epub ahead of print]
Is Thyrogen use common? What do other "thyroid experts" think about the use of Thyrogen?
Although Thyrogen is still a relatively new drug, it is gaining increasing acceptance as a useful tool for monitoring patients with thyroid cancer without significantly disrupting patients health (by avoiding hypothyroidism during scanning). For an overview of Thyrogen use see Using recombinant human TSH in the management of well-differentiated thyroid cancer: current strategies and future directions. Thyroid 2000 Sep;10(9):767-78.
Thyrogen seems to be a new drug with limited information about how it compares with the old way of doing things, namely withdrawal of thyroid hormone. How good is it?
We do not yet have long term follow-up data for thousands of patients who had Thyrogen scans. Nevertheless, as Thyrogen is a recombinant protein version of the protein normally produced in our bodies (TSH), it is expected to be safe. Other recombinant human proteins have been used as pharmaceuticals for many years without problems (insulin growth hormone, erythropoetin etc). To compare the diagnostic accuracy of Thyrogen testing versus withdrawal from thyroid hormone, see Analysis of the Results of Phase III Controlled Clinical Trials with Recombinant Human Thyrotropin: Developing a Clinical Guide. Endocr Pract. 2000 Oct;6(5):391-395. Although earlier studies suggested that Thyrogen scans were about 5-10% less accurate in detecting thyroid cancer recurrence compared to thyroid hormone withdrawal, some retrospective studies suggest that the results obtained with the 2 techniques may be comparable. See Preparation by Recombinant Human Thyrotropin or Thyroid Hormone Withdrawal Are Comparable for the Detection of Residual Differentiated Thyroid Carcinoma. J Clin Endocrinol Metab. 2001 Feb 1;86(2):619-625.
Nevertheless, there have been reports of instances where recombinant TSH was NOT as sensitive in picking up residual thyroid cancer compared to the more traditional method of withdrawing from thyroid hormone, as outlined in Two cases of thyroid carcinoma that were not stimulated by recombinant human thyrotropin. J Clin Endocrinol Metab. 2004 Feb;89(2):585-90.
How often should I have recombinant TSH testing for thyroid cancer follow-up?
The answer to this question is not yet clear, and will differ depending on the type of cancer, initial findings after treatment, years after initial treatment, and potential presence of other associated risk factors and medical conditions. For the opinion of one group of experts see Practical application of recombinant thyrotropin testing in clinical practice. Endocr Pract. 2001 May-Jun;7(3):195-201. For example, some analyses suggest that if a patients has a negative scan and ultrasound and undetectable thyroglobulin after an initial TSH-stimulated test, a second TSH-stimulated thyroglobulin is of limited value Predictive value of recombinant human TSH stimulation and neck ultrasonography in differentiated thyroid cancer patients Thyroid. 2008 Oct;18(10):1049-53.
Is there any risk to stimulating tumor growth or swelling after Thyrogen?
At present, there is little data to support a rapid change in tumor growth after two Thyrogen injections. A few patients with extensive thyroid cancer have developed local swelling, likely due to inflammation, at the site of recurrent tumor, that responded to treatment with steroid hormones. Hence, the risks of adverse events after Thyrogen administration are very low, but no medication, including Thyrogen, should be viewed as completely free of any potential side effects. See Sudden Enlargement of Local Recurrent Thyroid Tumor after Recombinant Human TSH Administration. J Clin Endocrinol Metab. 2001 Nov;86(11):5148-51 and Near-lethal respiratory failure after recombinant human thyroid-stimulating hormone use in a patient with metastatic thyroid carcinoma. Thyroid. 2003 Aug;13(8):827-30.
What is more sensitive in detecting residual thyroid cancer, the thyroglobulin blood test, or the whole body scan?
Although these tests give different and often complementary types of information, most studies show that the thyroglobulin blood test is slightly more sensitive at detecting small residual amounts of thyroid cancer, when the test is done in the hypothyroid state, or following administration of recombinant TSH. See Prediction of Disease Status by Recombinant Human TSH-Stimulated Serum Tg in the Postsurgical Follow-Up of Differentiated Thyroid Carcinoma. J Clin Endocrinol Metab. 2001 Dec 1;86(12):5686-5690. In general, even a modest rise in the level of thyroglobulin after recombinant TSH administration should prompt a search for the possibility of metastases Clinical value of different responses of serum thyroglobulin to recombinant human thyrotropin in the follow-up of patients with differentiated thyroid carcinoma. Thyroid. 2005 Mar;15(3):267-73
I have heart disease. Is Thyrogen a safe test for me?
Although this question cannot be answered with 100% certainty, the cardiac effects of Thyrogen has been studied in 11 patients, with no adverse effects noted on EKG parameters or on cardiac function as assessed by echocardiography. See Cardiovascular Safety of Acute Recombinant Human Thyrotropin Administration to Patients Monitored for Differentiated Thyroid Cancer.J Clin Endocrinol Metab. 2003 Jan 1;88(1):211-214.
Has Thyrogen been studied in children or adolescents?
Recombinant TSH safety and levels of TSH following Thyrogen administration have been examined in a retroespctive study of 100 patients 5-18 years of age in a multi-center study of young subjects with thyroid cancer. This was not a head to head analysis of rTSH vs. withdrawal. Most patients were administered the drug for diagnostic purposes (61%), some for therapeutic remnant ablation (18%) or treatment of more advanced disease (20%). Nausea and vomiting were the most common adverse events and occurred in less than 55 of subjects. The majority of patients achieved a peak TSH of more than 25 mU/L. The drug appears to be relatively well tolerated and useful in this patient population. J Clin Endocrinol Metab. 2009 Oct;94(10):3948-53. Recombinant thyrotropin use in children and adolescents with differentiated thyroid cancer: a multicenter retrospective study.