The protocol for follow-up of patients with well differentiated thyroid cancer will differ from center to center. In many centers, patients will be initially seen at 6 month intervals. Once it appears that the thyroid cancer has been successfully treated, with no evidence for residual disease on physical examination, scanning, or thyroglobulin testing, follow-up may be scheduled at yearly intervals for many patients. Routine follow-up assessment will include physical examination focused on the  and neck, and blood tests, including TSH and thyroglobulin. Periodic chest X rays may also be indicated. Although patients with thyroid cancer have traditionally been followed with periodic outpatient radioactive iodine scans, the low yield from this procedure has led to a reassessment of the need for regular thyroid hormone withdrawal and iodine scanning. A consensus-based review of available literature led to the recommendation that recombinant TSH-stimulated  (Thyrogen) thyroglobulin testing be the primary test for follow-up of patients, and the much lower sensitivity and specificity of the total body scan has led to the de-emphasis of this test on a routine basis, as recommended in A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma. J Clin Endocrinol Metab. 2003 Apr;88(4):1433-41.

The use of Recombinant TSH (Thyrogen) for TSH-stimulated thyroglobulin blood tests eliminates the need for withdrawal of thyroid hormone and the development of hypothyroidism.

In patients who have thyroid cancer confined to the thyroid, with no evidence of extra-thyroidal disease at the time of surgery  or on the first total body radioactive iodine scan, with an undetectable TSH-stimulated thyroglobulin,  it may not be necessary to have periodic or regular thyroid scans.

Alternatively, some patients with more extensive thyroid cancer may have disease outside the thyroid bed, or evidence for abnormal iodine accumulation outside the thyroid bed on the radioactive iodine scan after the initial radioactive iodine treatment. For these patients, initial periodic rescanning with radioactive iodine as an outpatient may be considered. Nevertheless, the accuracy of routine scanning for follow-up of thyroid cancer has been questioned, as some studies have shown that the thyroglobulin level is a better predictor of disease recurrence than a nuclear medicine scan, as discussed in J Clin Endocrinol Metab 2000 Jan;85(1):175-8 Is diagnostic iodine-131 scanning useful after total thyroid ablation for differentiated thyroid cancer?. Furthermore, in patients who have an undetectable thyroglobulin after their first withdrawal of Thyrogen scan, the utility of a subsequent total body iodine scan appears questionable, as outlined in Diagnostic 131-iodine whole-body scan may be avoided in thyroid cancer patients who have undetectable stimulated serum Tg levels after initial treatment. J Clin Endocrinol Metab. 2002 Apr;87(4):1499-501.

The superior performance and enhanced sensitivity of the TSH-stimulated Tg test alone, compared to the inclusion of the whole body scan plus Tg, for the detection of recurrent or residual thyroid cancer was also apparent in Is Diagnostic Iodine-131 Scanning with Recombinant Human TSH Useful in the Follow-Up of Differentiated Thyroid Cancer after Thyroid Ablation? J Clin Endocrinol Metab. 2002 Apr;87(4):1490-8 as reviewed in Management of low-risk well-differentiated thyroid cancer based only on thyroglobulin measurement after recombinant human thyrotropin. Thyroid. 2002 Jul;12(7):583-90. Newer Tg assays may have improved sensitivity and may be more useful for following trends of Tg in the diagnosis of recurrence but a TSH-stimulated Tg is still likely to be more sensitive, even with the newer assays, for monitoring of thyroid cancer-see Comparison of seven serum thyroglobulin assays in the follow-up of papillary and follicular thyroid cancer patients. J Clin Endocrinol Metab. 2007 Apr 10; [Epub ahead of print]

Repeat diagnostic scanning for thyroid cancer recurrence has traditionally involved withdrawal of thyroid hormone, rendering patients hypothyroid. Thyroxine may be completely withdrawn for 3-4 weeks, or patients may be switched to T3, which can then be withdrawn for ~ 2 weeks. It has been necessary to make patients hypothyroid for the scan to be informative, as the pituitary production of TSH maximally stimulates uptake of the diagnostic dose of radioactive iodine. The exact amount of radioactive iodine administered for the diagnostic total body scan may vary from center to center, but frequently is ~ 5 mCi. In contrast, the amount administered for therapeutic treatment of thyroid cancer may range from 100-200 mCi. The scan is usually done as an outpatient, hence there is no need for isolation or extreme precautions. Common sense dictates that a small amount of radioactive iodine may be present in body fluids for a few days after the scan, so avoiding intimate exchange of body fluids, shared foods, prolonged kissing etc, may be reasonable for a few days after the administration of radioactive iodine. There have been no studies done to address the issue of when it is "perfectly safe" to try and conceive a child after a diagnostic 5 mCi scan. Waiting at least one cycle for the radioactivity to clear the system seems to be a prudent approach. 

At the same time as the scan is done, a blood test for TSH and the thyroglobulin protein should also be done. As it can take a few days for the test results to become available, some patients may go back on T3 (Cytomel) while waiting for the all results to be transmitted to their physician. These specific issues should be discussed with your physician. Thyroglobulin is reported in different units, either ng/ml=ug/L or pMol/L. To convert the units, 1 ng/mL Tg = ~1.515 pmol/L.

At the Toronto General Hospital, normal values are:

Download a Summary Sheet of Instructions for Follow-up Testing.

To arrange either Thyrogen or Withdrawal testing with a Thyroglobulin blood test and a total body scan, download the Sheet of Instructions for Follow-up Testing.complete the form and Fax to Dr. Drucker's office.

Since the exact protocol for follow-up of patients with thyroid cancer can vary widely depending on the initial pathology, staging, type of cancer, and philosophy of the thyroid cancer physician, it seems prudent for each patient to discuss the nature and frequency of follow-up visits with their thyroid cancer physician.

TSH suppression

Several studies have shown the importance of keeping the TSH suppressed during ongoing management of patients with thyroid cancer. The standard therapy for patients with thyroid cancer is Treatment with L-thyroxine. For an overview, see L-thyroxine and thyroid cancer.  Physicians who do not routinely look after patients with thyroid cancer may receive lab reports indicating that the TSH is abnormally low and suppressed and be tempted to lower the dose of thyroid hormone. Accordingly, it is suggested that any changes to the dose of thyroid hormone in patients with thyroid cancer be done in consultation with physicians experienced in the care of thyroid cancer patients.

FAQs

Although I have had the complete treatment and reassurance that everything is fine, I am still extremely worried. Is this common?

The diagnosis of thyroid cancer is a shock, for almost everyone. For an overview of the anxiety and emotional reactions associated with this disease, see Psychological Impact of a thyroid cancer diagnosis.

My thyroglobulin levels are low or undetectable. Does this guarantee that my thyroid cancer has not returned?

Although the majority of well differentiated thyroid cancers will produce thyroglobulin, this is not always the case. Accordingly, it is possible for thyroid cancer to recur, yet the thyroglobulin levels may be low or undetectable. Hence the thyroglobulin alone is not 100% perfect in the follow-up of patients with thyroid cancer. For a representative study, see Thyroid 2000 Feb;10(2):171-6 Recurrent differentiated thyroid cancer without elevation of serum thyroglobulin and Neck recurrence from thyroid carcinoma: serum thyroglobulin and high-dose total body scan are not reliable criteria for cure after radioiodine treatment. Clin Endocrinol (Oxf). 2005 Mar;62(3):376-9.

Nevertheless, a low thyroglobulin after initial surgery seems to be a useful prognostic sign, as outlined in Predictive value of serum thyroglobulin after surgery for thyroid carcinoma. Laryngoscope. 2003 Jan;113(1):77-81 and Predictive Value for Disease Progression of Serum Thyroglobulin Levels Measured in the Postoperative Period and After (131)I Ablation Therapy in Patients with Differentiated Thyroid Cancer. J Nucl Med. 2004 Jun;45(6):988-994 and Prognostic value of thyroglobulin serum levels and 131I whole-body scan after initial treatment of low-risk differentiated thyroid cancer. Thyroid. 2004 Apr;14(4):301-6.

How will I feel when I am on the Cytomel or T3 for several weeks?

The majority of patients feel fine. Since patients taking T3 are often mildly hyperthyroid, especially if they are taking two tablets a day, some patients even feel better on T3 compared to how they feel on l-thyroxine. Falling withdrawal of T3, patients may feel a bit tired and achy, as if they have a mild flu or cold. Three weeks of withdrawal from thyroxine appears to be sufficient for most patients undergoing diagnostic testing as described in Health-Related Quality-of-Life Study in Patients With Carcinoma of the Thyroid After Thyroxine Withdrawal for Whole Body Scanning. Laryngoscope. 2006 Nov; 116 (11) :2060-2066

I just had my follow-up total body scan and it was negative. Can I restart my thyroid hormone?

In addition to the results of the scan, it is 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 go stay off thyroid hormone completely or start back on T3 (Cytomel) while waiting for the results of the thyroglobulin, depending on your physicians recommendation.

My total body scan is negative but my thyroglobulin is elevated. What should I do?

This scenario may have several explanations. First, it is important to make sure that the thyroglobulin is not falsely elevated as a result of antibodies. In some instances, small amounts of tumor may be present that are too small to be visualized on the scan, but active enough metabolically to produce thyroglobulin. In other cases, the cancer cells may make thyroglobulin, but they may have lost the ability to take up radioactive iodine. In this type of situation, some physicians will advocate an empiric treatment with high dose radioactive iodine, followed by a repeat total body scan, as outlined in Effects of therapeutic doses of 131I in thyroid papillary carcinoma patients with elevated thyroglobulin level and negative 131I whole-body scan: comparative study. Clin Endocrinol (Oxf). 2003 Apr;58(4):421-427. It is not uncommon for a single abnormal thyroglobulin to be elevated, followed by a repeat blood test a few months later where the thyroglobulin may be lower, or even undetectable. In other cases, where the thyroglobulin blood test abnormality persists, additional imaging studies may be requested, such as a neck ultrasound, high resolution CT scan, MRI, or in centers equipped with the technology, a PET scan. To review studies of this issue, see Treating the patient with differentiated thyroid cancer with thyroglobulin-positive iodine-131 diagnostic scan-negative metastases: including comments on the role of serum thyroglobulin monitoring in tumor surveillance. Semin Nucl Med. 2000 Apr;30(2):107-14, and Management of patients with differentiated thyroid cancer who have positive serum thyroglobulin levels and negative radioiodine scans. Thyroid. 1994 Winter;4(4):501-5. and Utility of fluorine-18-fluorodeoxyglucose positron emission tomography in differentiated thyroid carcinoma with negative radioiodine scans and elevated serum thyroglobulin levels and Am J Surg. 2000 Jun;179(6):457-61. and FDG PET of recurrent or metastatic 131I-negative papillary thyroid carcinoma. J Nucl Med. 2000 Jun;41(6):1010-5.  and Comparison of (18)F-FDG, (131)I-Na, and (201)Tl in Diagnosis of Recurrent or Metastatic Thyroid Carcinoma. J Nucl Med. 2001 Mar;42(3):414-9. and Preoperative diagnostic value of [18 f] fluorodeoxyglucose positron emission tomography in patients with radioiodine-negative recurrent well-differentiated thyroid carcinoma. Ann Surg. 2001 Dec;234(6):804-11. and The clinical impact of 18F-FDG PET in papillary thyroid carcinoma with a negative 131I whole body scan: a single-center study of 108 patients. Ann Nucl Med. 2006 Oct;20(8):547-52

The diagnostic sensitivity of PET scans for detection of occult thyroid cancer may be higher in patients with TSH elevations, either induced by administration of recombinant TSH, or by withdrawal from thyroid hormone. See Better Yield of 18Fluorodeoxyglucose-Positron Emission Tomography in Patients with Metastatic Differentiated Thyroid Carcinoma during Thyrotropin Stimulation. Thyroid. 2002 May;12(5):381-7.   However, not all centers have reported good experiences with PET scans when searching for recurrent thyroid cancer as outlined in The Value of Positron Emission Tomography in the Surgical Management of Recurrent Papillary Thyroid Carcinoma. World J Surg. 2008 Jan 20; [Epub ahead of print]

 

This is a controversial and challenging management area and the patient is advised to seek the counsel of a physician experienced in the management of thyroid cancer. Despite the apparent success of empiric radioactive iodine in some  Tg-positive scan-negative patients, some studies have reported a lack of therapeutic success with this empiric approach, especially in patients with the follicular variant of thyroid cancer. See Lack of impact of radioiodine therapy in Tg-positive, diagnostic whole-body scan-negative patients with follicular cell-derived thyroid cancer. J Clin Endocrinol Metab. 2002 Apr;87(4):1521-6.

Although a combination of whole body scanning after radioactive iodine AND measurement of circulating thyroglobulin represents an effective strategy for assessment of residual thyroid remnants and thyroid cancer in most patients, a small subset of patients have normal total body scans but elevated levels of thyroglobulin. After excluding assay-associated artifacts, the use of PET scans (see data above and studies below) appears to result in considerably enhanced sensitivity for detection of residual thyroid cancer that may be below the threshold for detection by convention 131-I scanning. It appears appropriate to recommend the use of PET scans for patients with unexplained increases in thyroglobulin with negative imaging studies using conventional radiological techniques. See Clinical impact of (18)f-fdg pet in thyroid carcinoma patients with elevated thyroglobulin levels and negative (131)i scanning results after therapy. J Nucl Med. 2001 Oct;42(10):1464-9 and Implication of 2-18fluor-2-deoxyglucose positron emission tomography in the follow-up of Hurthle cell thyroid cancer. Thyroid. 2002 Feb;12(2):155-61. and Therapeutic impact of 18FDG-PET/CT in the management of iodine-negative recurrence of differentiated thyroid carcinomaSurgery. 2007 Dec;142(6):952-8

I can't decide whether to have a total body scan with Thyrogen, or go off thyroid hormone? Which is better?

The traditional method for doing a total body scan for the follow-up of patients with thyroid cancer is to go off thyroid hormone completely. This may involve switching to a short acting medication such as T3 (Cytomel) which will then need to be stopped for 10 days to 2 weeks. This method produces a TSH elevation permitting an assessment of iodine uptake by any remaining thyroid cells, and a blood test (thyroglobulin) is also done at this time when the TSH is maximally elevated. 

Unfortunately, stopping thyroid hormone to achieve a TSH elevation implies that the patient is significantly hypothyroid. In some patients, this may be well tolerated without untoward side effects. Other patients may feel unwell, tired, achy, bloated and have trouble with normal cognitive function for the 4-8 weeks that surround the hypothyroid state (2 weeks before, 4-6 weeks after). There is data documenting the condition of hypothyroid patients who are being withdrawn from thyroid hormone, and some patients clearly experience decreased cognitive function and feel unwell, as shown in Hypothyroidism and cognition: preliminary evidence for a specific defect in memory. Thyroid. 2001 Dec;11(12):1177-85.

In contrast, Recombinant TSH (Thyrogen) allows the diagnostic testing (thyroglobulin and total body scan) to be done without becoming hypothyroid, but Thyrogen is expensive, and in some earlier studies, but not subsequent studies, it may be slightly (5-10%) less sensitive than withdrawal from thyroid hormone. 

The type of testing you have done (withdrawal from thyroid hormone versus Thyrogen) depends on your personal circumstances, the clinical conditions, and patient preferences, integrating the above information into your decision making. Although the initial prospective clinical trials done to evaluate recombinant TSH versus thyroid hormone withdrawal suggested a slight increase in sensitivity with thyroid hormone withdrawal, a subsequent non-randomized retrospective study have shown near comparable results using either withdrawal, or recombinant TSH administration. 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; 86(2):619-25.

Are there any absolute predictors of adverse outcome for patients with thyroid cancer?  

Patient age, tumor size, and extra thyroidal spread at the time of diagnosis are among the variables that influence survival in patients with thyroid cancer. To review the results of a retrospective series of patients with the follicular variant of differentiated thyroid cancer, see J Am Coll Surg. 2000 Dec;191(6):600-6. Recurrence of thyroid cancer in local lymph nodes occurs in 10-15% of patients with papillary carcinoma of the thyroid, and in younger patients less than 45 years of age, is not associated with an adverse prognosis. See Prognosis after lymph node recurrence in papillary thyroid carcinoma depends on age. Thyroid. 2001 Oct;11(10):953-7.

I have heard that special scans with labeled octreotide or somatostatin can be useful for detecting some types of thyroid cancer, is this correct?

There are a few preliminary studies of whether somatostatin-based imaging studies can detect some forms of thyroid cancer. The data appear to be most promising for Hurthle cell carcinomas, especially when the scan is done in the presence of an elevated thyroglobulin test. See Radionuclide-labeled somatostatin analogues for diagnostic and therapeutic purposes in nonmedullary thyroid cancer. Thyroid. 2001 Jul;11(7):647-59.

What is the prognosis for patients with well differentiated thyroid cancer?

There are dozens of studies reporting survival and prognosis in patients with thyroid cancer. In general patients with this disease have an excellent prognosis, although recurrence is not uncommon since patients survive for decades. In one retrospective report from Toronto that included analysis of over 300 patients, the recurrence rate was 15.6%. The overall and disease-specific survival at 10 years was 97.5% and 98.5%, respectively, and the overall and disease-specific survival at 20 years was 88.4% and 93.3%, respectively. See Prognostic Factors in Well-Differentiated Thyroid Carcinoma. Laryngoscope. 2004 Dec;114(12):2110-2115. Similarly, patients with follicular variant of papillary thyroid cancer have the same excellent prognosis compared to patients with regular papillary thyroid cancer Classical and Follicular Variant of Papillary Thyroid Carcinoma: A Comparative Study on Clinicopathologic Features and Long-term Outcome. World J Surg. 2006 Apr 17;

What factors predict the basal Thyroglobulin and the response to recombinant TSH?

Although it is difficult to generalize, histological tumor subtype, and the site of extrathyroidal extension differentially influence the basal Tg vs. the response to recombinant TSH. See Factors influencing the Basal and recombinant human thyrotropin-stimulated serum thyroglobulin in patients with metastatic thyroid carcinoma. J Clin Endocrinol Metab. 2004 Dec;89(12):6010-6.

How often do I need to have a TSH-stimulated thyroglobulin (Tg) test, either with Thyrogen or after withdrawal from thyroid hormone?

The answer depends on the initial presentation and stage of the tumor, the pre-and post-treatment thyroglobulin, and the results of the most recent TSH-stimulated Tg. Generally, patients with an undectable TSH-stimulated Tg have an excellent prognosis, extremely low risk of recurrence, and would need less frequent re-testing. In contrast, patients with a TSH-stimulated Tg of greater than 2 need more frequent F/U and imaging studies. See A Single Recombinant Human Thyrotrophin-stimulated Serum Thyroglobulin Measurement Predicts Differentiated Thyroid Carcinoma Metastases Three to Five Years Later. J Clin Endocrinol Metab. 2005 Jun 21;