Ask Thry'vors Archive Categories

• Beginnings
• Pathology and Cytology
• Surgery
• Treatment and Follow-up
• Radioactive Iodine
• Low Iodine Diet
• Thyroid Hormone Replacement and TSH Level
• Psychological impact of Thyroid Cancer
• Other Related Health Issues
• Women's Issues
• Men's Issues
• Children and Youth Issues

Treatment and Follow-up

1. Can thyroid cancer remain static and relatively unchanged over time despite its location and Tg level?

   Tamilia (Jan 2012)

   Q: We have a few patient-members who were diagnosed with lung metastases 20 or more years ago, but their cancer seems to remain static and relatively unchanged over time despite its location and Tg level.  How is this explained?

   A: We don't know. It is difficult to accurately  predict the biological behaviour of malignancies.  The final outcome after appropriate therapy does not only depend on tumor factors but also patient factors (? immunity, local tissue response, etc)

2. How high a Tg level is possible (ie. have you been aware of in a patient?)

   Tamilia (Jan 2012):
   This depends if the lab routinely dilutes their specimen with results >300ug/L.   I have patients with distant metastases and unstimulated serum Tg levels in the 10,000ug/L range without antibody interference

3. How are Tg levels interpreted in regards to the clues they give to location of metastases?

   Cheng (June 1/11)

   The thyroglobulin (Tg) level only provides us with a rough clue as to the location of the metastasis.  Generally, in order of ascending Tg level, the sites of metastases are neck, mediastinum, lung and bone.  However, citing any specific numbers is difficult.  A 2004 study in the Journal of Clinical Endocrinology and Metabolism reported wide ranges of prestimulated Tg levels but the median prestimulated Tg levels (ug/L) were 687 for bone, 34 for lung, 25 for mediastinum and 10 for neck.  The highest reported prestimulated reading in the study was 65400 ug/L. 
   
   Ezzat (June 1/11)

   Thyroglobulin (Tg) levels are used as a surrogate marker of differentiated thyroid tissue. Levels should decline to less than 2 following stimulation in the absence of any thyroid tissue such as following surgery and radioactive iodine ablation. Mildly elevated levels in the 2-10 range can indicate residual and/or recurrent disease of low volume. This is often disease which is small enough to evade detection by imaging studies. As levels increase from 10 to 100 the chances of detecting disease in the neck where lymph nodes capture the thyroid cancer cells increase. Levels can rise well into the thousands indicating wider invovlement. The exact site, however, cannot be asertained. Statistically speaking, such high levels typically indicate lung involvement. This can remain stable for many years without further progression. This latter feature must be cautiously interpreted in making therapeutic decisions which may or may not impact on disease progression.
   
   
   Tamilia (June 1/11)

   In an effort to answer this question I will assume that we are dealing with well-differentiated thyroid cancer (papillary, ptc or follicular, ftc), that our index patient has undergone primary therapy for thyroid cancer, and that there is no interference from Tg-antibodies.  I am aware of two retrospective studies, one from Institute Gustave Roussy and one from Mount Sinai, NY, that report a good positive correlation between stimulated  serum Tg  levels and tumor burden.  Basically, levels are higher among patients with ftc compared to ptc, macro -metastases vs micro metastases and local vs distant metastases these factors being equal,  stimulated Tg are in the 10's with node mets, in the 100's with lung mets and in the 1000's with bone mets.

4. What is the likelihood of developing a secondary cancer as a result of EBR treatment for thyroid cancer

   Brierly (Jan 1/11)

   External beam radiotherapy can cause second cancers many years or decades after radiation treatment. The commonest types of second cancers are breast, lung, and thyroid soft tissue. Generally to be considered to be a second cancer that may be caused by external beam radiotherapy the tumour is within previously irradiated tissue, the time from radiotherapy to secondary malignancy is biologically plausible (at least 5 years usually much longer), and the second malignancy is a different histology from the primary.
   
   The salivary gland tumour and the spinal cord tumour, although unusual as second cancers, could be if they were in the area that received some radiation. Her oncologist should be able to answer this for her.
   
   The type of delivery of the radiation; cobalt or linear accelerator, does not affect the risk.

5. Is it common for the antibodies measurement to become undetectable over time as RAI continues to ablate the remnant tissue? Is a corresponding Tg measurement considered to be so unreliable as to make it totally insignificant in meaning?

   Cheng (Aug 1/10)

   If the radioiodine ablation was successful, one would expect that the anti-Tg antibody levels would also become undetectable over a matter of months to years. If anti-Tg antibodies are present, the Tg level is considered completely unreliable and the levels can not be used for monitoring. That is because the presence of anti-Tg antibodies can sometimes raise the Tg reading or lower the Tg reading. The current guidelines suggest that one could use the level of anti-Tg antibody as an inexact indicator that there may be recurrent disease if the level starts to rise.
    

6. What is the difference between Thyroglobulin testing values under stimulated or non-stimulated conditions. How do you interpret them clinically as to the difference in their importance?

   Cheng (Aug 1/10)

   Thyroglobulin (Tg) is a substance that is only made by thyroid cells. Therefore, we can use Tg levels to help us monitor for recurrence of thyroid cancer after someone has had their entire thyroid removed and they have had radioiodine ablation. Thyrogen or withdrawal causes the TSH level to rise, which results in stimulation of any remaining thyroid cells (cancer or normal) to make thyroglobulin. Therefore, if the Tg level is undetectable, even when stimulated, we can be confident that there are no remaining thyroid cells. However, under non-stimulated conditions, the person is on thyroid replacement and their TSH is purposely kept low. When Tg is measured under those circumstances, an undetectable value is good but not 100% reassuring because if there were only a small number of thyroid cells, they may not make enough Tg to be detected when not stimulated, but would make enough if stimulated. Therefore, clinically, stimulated Tg is much more useful when monitoring for recurrence of disease compared to non-stimulated.

7. Do Anti-thyroglobulin antibodies vary?

   A patient asks if her large rise in AntiTg recently can be accounted for by the developments in making AntiTg blood test assays more sensitive than they were in the past. Her endocrinologist is repeating her test in a different lab to try to confirm whether this change in Tg antibodies can be accounted for as a test anomaly, as opposed to an indication of recurrence. Please comment on this, and the changing developments in Tg assays.
   
   

   Ezzat (Jan 1/10)

   This is an interesting and important question. Thyroglobulin measurements represent the mainstay of monitoring the most common form of thyroid cancer. Thyroglobulin is produced by papillary cancer and levels generally decline following surgery and radio-active iodine ablation. One important caveat, however, is the presence of antibodies to thyroglobulin. This can result in false over or under-estimation of the true thyroglobulin value. Laboratory methods for measuring anti-thyroglobulin antibodies fall into two major classes. Those which are qualitative and expressed as a "titer" value eg: 1:1600 and those which represent absolute measurement expressed in molecular weight units such as ng/ml. Within each class are a number of methods for the reference range of normal values. Thus, for accurate interpretation of values, it's important to compare measurements made using the same method, ideally, in the same lab.
   
    

8. Is there an alternative method of ablation of lymph nodes?

   Since there is the ability to try to ablate thyroid cancer tumours in lymph nodes by injecting ethanol into them (during Percutaneous Ultrsound-Guided Ethanol Ablative Therapy) is it not also possible as an alternative, to inject a small amount of radioactive iodine into affected nodes?
   
   Ezzat (Nov 1/09)
   
   Injection of ethanol into tissue is a very old method used where other therapies have failed or not technically possible. While it may seem simple at first glance, there are significant problems associated with this practice. Firstly, injecting any tissue without firm diagnosis is not appropriate as the anticipated response cannot be accurately predicted. As the alcohol destroys the tissue, it has the potential to seep into surrounding structures causing wider damage. Finally, there is no assurance that the majority of tumour cells will be killed. Thus, it's always preferable to remove the suspected disease, confirm its identity through detailed surgical pathology examination, which together dictate the need, if any, for additional treatment and/or monitoring. Similarly, there is no added benefit from directly injecting radio-iodine by an injection. When consumed by mouth, all tissues which contain thyroid cancer cell elements, regardless of their size or location, will take up the radio-iodine thus targeting the radiation more accurately to where it is needed.

9. What are the long term effects of having been treated with RAI?

   Driedger (Oct 1/05, revised Sept 26/08)

   In terms of the long term effect of RAI, the answer to the question is complex. In general, all forms of ionizing radiation can cause cancers, leukemia or bone marrow dysplasias. The frequency with which these things happen is a function of the dose, the dose rate, the form of radiation and probably also of the patient’s genetic make-up. Fortunately, ionizing radiation is relatively inefficient in the production of cancers compared to many chemicals. There is a great deal of debate about whether low doses of radiation actually cause cancers or other damage because most of us have complex DNA repair systems in our cells. There is even evidence that low doses may be protective against the bad effects of subsequent high radiation doses. Also, the induction of cancer is not a single step event; if the subsequent events following radiation injury do not occur then the cancer will not result from the exposure.

   In the early years of radioactive iodine usage, there were some cases of leukemia noted in patients who had received radioiodine. The protocols of that time were different and the recent literature does not report the same incidence of leukemia as was noted 35 years ago. We try to leave intervals of 6-12 months between treatments these days and perhaps this allows more time for the normal cells to heal before the next exposure. As regards other solid cancers, the data are complex. One recent study concerning the incidence of second cancers in more than 2 million Americans found that there was about a 3-fold increase in thyroid cancer diagnosis within one year of diagnosis of a non-thyroid cancer. There was also a smaller increase in other cancers in the first year following a thyroid cancer treatment. The conclusion was that the second cancers appeared too soon to have been caused by treatment of the first cancer.

   We expose patients to radiation only when there is something more to be gained from the exposure in order to compensate for the risks. There is no point in not treating a cancer that the patient already has in order to avoid the small risks of inducing another cancer. Thus, in my view, there is not a life-long limit to the cumulative dose of radioiodine for any patient. On the other hand, as one administers serial treatments to a patient, one learns about the response of the individual cancer to the treatment. Many times, one comes to the conclusion that radioiodine is no longer the appropriate form of treatment for the patient; then we stop but not simply because a dose limit has been reached. At other times, the bone marrow or another organ can not tolerate additional dosage and we stop for that reason.

10. What are my chances of having a recurrence?

    Rosen (Nov 1/06)

    (Excerpt from Dr. Rosen's Lecture on Thyroid Cancer Recurrence) "When one looks at the Canadian Cancer Society statistics, one has to recognize that thyroid cancer in MALES makes up 0.9% of all new cancer cases, while prostate at about 27%, lung at 16%, and colorectal cancer at 14% are far more frequent. Thyroid cancer results in 0.2% of all cancer deaths in males, while lung makes up 30%, colorectal cancer and prostate cancer about 12% each of the male mortality."

    "In FEMALES, thyroid cancer makes up only 3% of new cancers which is well ahead of such well known entities as melanoma, pancreas, leukemia, or Hodgkin's disease. In females, thyroid cancer makes up 0.3% of all mortalities due to cancer as compared to 26% for lung, 16% for breast or 12% for colorectal cancer."

    "Conclusion: Patients may resent medical over-reassurance regarding the nature of thyroid cancer but it must still be recognized that thyroid cancer is indeed the "best type" of malignancy to have. If one looks at the other malignancies that affect mankind, thyroid cancer is a shining example in contrast because of excellent response to reasonable management. There is no other malignancy that can approximate the outcome of thyroid cancer. This does not mean that patient's concerns, questions and anxieties should be dismissed or treated in a cavalier fashion nor should one assume an overly pessimistic attitude when dealing with thyroid cancer and its subsequent problems. Surveillance should be set up on a periodic basis following the initial treatment and should be on a lifetime basis."

    Editor’s Note:To read more about thyroid cancer recurrence and management, see Dr. Rosen's Wally Patching Memorial Lecture 2005.

11. How can one’s disease be treated if their tumours are non-avid (ie. are, or have become less well-differentiated)?

    Ezzat (July 1/05)

    (In regards to RAI non-avid persons) the options include surgical debulking if the disease is accessible. Occasionally, the disease is monitored conservatively. If there is clinical evidence of disease progression, external beam radiation and/or novel therapeutic agents can be explored.

    Driedger (July 1/05, revised Sept 26/08)

    (In regards to RAI non-avid persons) the treatment options for iodine-negative thyroid cancer depend somewhat on where the cancer is and on what symptoms the patient is experiencing. Local thyroid bed and neck lymph node recurrences are amenable to surgery in many cases.  If the patient has acute symptoms, such as airway compression or a fracture, then external beam irradiation has an important role to play.

12. How does one know if they have RAI-resistant (or non-avid) metastases?

    Driedger (July 1/06, revised Sept 26/08)

    Those patients who have a persisting elevation of their Tg level often are given an additional therapy dose of 131I and this will include a post-therapy scan several days later. There should always be blood drawn for Tg testing at the time of the treatment.  When there is a discordance between the scan (ie, normal) and Tg (elevated), then one has to suspect iodine-negative cancer. These patients then need to undergo additional imaging, most often CT of the neck and chest and ultrasound of the neck.

    In the case of RAI resistance, does it ever happen that the cells change and the patient is able to concentrate RAI again?

    Unfortunately, no. Iodine uptake is a sophisticated feature of thyroid tissue and if tumours become more malignant over time, they sometimes lose this feature.

13. What is pre-therapy dosimetry and how and why is it used in some cancer centres?

    Driedger (Feb 1/08, revised Sept 26/08)

    These are regional variations in protocols that patients notice but which aren't important to the outcomes. Traditionally it was the practice to check on the amount of residual thyroid function after surgery before giving radioactive iodine. Those centres that do pre-therapy dosimetry will measure the uptake over several days before calculating the required dose of iodine. On the other hand, the time taken to do dosimetry allows time for "stunning" to occur and this may reduce the therapeutic effectiveness of the administered dose. Stunning is a controversial issue over which even the most experienced nuclear physicians hold divided opinions and variations in protocols reflect the diversity of opinions. My observations convince me that the stunning effect is real and can be detrimental to the subsequent treatment. For this reason, we and many, if not all, Canadian centres use a standardized dosage protocol that does not require dosimetry to be performed.

    The other reason for not doing a pretherapy uptake is that since some centres have moved to the use of Thyrogen-stimulated ablation, the timing of essential activities does not allow for the administration of a diagnostic or dosimetric dose of 131I.

    You will appreciate that in this matter, as well as other aspects of thyroid cancer therapy, there is a diversity of opinions from centre to centre. This is no different from other areas of medical practice. What is important is that we have not, so far, been able to demonstrate that any one protocol is clearly superior to another.

14. What does it mean if I have anti-Tg antibodies in my bloodwork, ie. when my Tg was assessed?

    Driedger (May 1/07, revised Sept 26/08)

    The presence of anti-Tg antibodies above normal is a reason for caution when evaluating the significance of the Tg result since the antibodies interact with Tg and falsely lower the value.

    The good news is that one can repeat the antibody test at intervals of a few months. If all normal thyroid tissue has been removed or destroyed, and if there is no cancer remaining, then the antibody levels will fall and may become normal.

    It rarely happens that the antibody levels will rise during follow-up, having previously been normal. When this happens, one must ask whether this is signalling a cancer recurrence. Tests such as ultrasound of neck, CT of chest and RAI scans may be required. In high risk cases one may even decide to administer an additional RAI treatment.

15. How and why are Thyrogobulin (Tg) levels tested?

    Driedger (Jan 1/06, revised Sept 26/08)

    After total thyroidectomy and appropriate RAI ablation, thyroglobulin (Tg) performed when the TSH is elevated is the most sensitive screening test we have for early detection of persistent or recurrent thyroid cancer. The level of Tg is nearly always reduced and often undetectable if TSH is suppressed. That is why the patient should be either hypothyroid or have received injections of Thyrogen prior to critical Tg measurements.

    A factor that can interfere with the measurement of Tg  is the presence of anti-Tg-antibodies; often this is a temporary problem and the anti-Tg-antibodies will disappear a few months after ablation of all thyroid cells. If it does not, then we rely on the RAI scan to assess cancer status.

    An elevated Tg should always raise the suspicion of underlying thyroid cancer. With a combination of ultrasound of neck, CT of chest and RAI and PET scans, we can find the cancer in about 50% of these cases.

    If anti-Tg antibodies remain elevated over a long period of time, one has to ask whether there is still some thyroid-related tissue (remnant or tumour) that is providing stimulation for the continued production of the antibodies. Fortunately, this doesn’t happen often.

16. What are the advantages to different imaging modalities in regards to thyroid cancer?

    Driedger (July 1/08, revised Sept 26/08)

    Each of the imaging modalities addresses a unique set of tissue characteristics and that is why they are not interchangeable.

    1. Ultrasound uses echoes from tissue planes and from moving objects, such as blood, to make its images. Therefore, ultrasound will recognize the tissue disorganization of a tumour or a cyst and it will also recognize alterations of blood flow that might distinguish between a normal lymph node or one with cancer within it.

    2. A CT scan makes images that are based on differences in the density of normal and abnormal tissues and the distribution of injected radiographic contrast (dye) in the tissues. A CT scan will easily recognize the presence of calcium in a tumour and the distribution of contrast will demonstrate the distribution of blood volumes within an organ.

    3. Nuclear scans, of which RAI is one example, image the distribution of targeted functions within the body. In the case of RAI, one is able to image the distribution of tissues that concentrate radioactive iodine; ie, normal thyroid and, under special circumstances, thyroid cancers.

    4. MRI is another way to image the anatomy of the body through imaging of the distribution of water within the body. Here one uses complex, controlled magnetic fields to influence the nuclear spins of hydrogen in order to create the image. MRI is not used often as an imaging technique in relation to thyroid diseases.

    5. PET is a special form of nuclear scan that uses a specific type of radioactive isotopes known as "positron emitters". The most commonly used PET isotope is fluorine-18 and it is bound to a sugar molecule known as glucose; the complete sugar-isotope complex is known as FDG. Most cancers are more dependent on a supply of glucose for their energy than normal tissues. Thus, when FDG in injected into the blood, it is strongly bound to cancers in an irreversible reaction and we are able to make images of the FDG distribution.

    These days PET scanners come with a CT scan so that the anatomic and functional images can be co-registered on each other. This enables us to distinguish more accurately between cancer and non-cancerous forms of disease and it enables us to locate the cancers more accurately (eg, for the surgeons and radiation oncologists). Thus, all PET scans are now done as combined PET and CT.

    In thyroid cancers the PET/CT scan is needed in a select set of cases when the patient has an elevated level of Thyroglobulin in the blood and the RAI and ultrasound scans have failed to demonstrate a site of disease. The results of the PET/CT scan are useful for the patient whether they are normal or abnormal. In our experience, abnormal scan results identified the location of disease accurately so that the surgeons were able to remove it in many cases. Normal scans in these patients indicate that the disease will progress very slowly, if at all and avoid further invasive treatments at the time.

17. Do thyroid cancer patients need to have follow-up RAI Scans? If not, how should thyroid cancer patients be followed?

    Driedger (Aug 1/06, revised Sept 26/08)

    The data show that the RAI scan lacks sensitivity in follow-up after ablation and that the stimulated Tg alone is sufficient in most cases. There are patients who must still be followed by scan on account of their anti-Tg antibody titres. 123-I is a better isotope for this than 131-I but there are cost, scheduling and supply issues with this isotope.

    A year ago we decided to look into the scan vs Tg issue for ourselves. I can now tell you that in several hundred cases the scan did not make a difference in any case. We have discontinued follow up scans when measuring Tg except for those mentioned above.

    In our practice we found that 23% of all patients had an undetectable thyroglobulin (Tg) at the time of ablation: In up to 8.5 years of follow up of this group there has been only one recurrence of disease. Another 60% had undetectable Tg when retested at 6 months and none of these has had a further problem so far. That left 17% who needed more attention and some additional treatments. Thus, we do not perform follow-up RAI without cause. The 2006 ATA guidelines support this practice. Once there has been an undetectable stimulated Tg, we would not repeat that measurement for at least 5 years based on individualized considerations.

    Ain (Sept 8, 2007 reference:http://health.groups.yahoo.com/group/thyroidcancerhelp/message/984)

    Although a very useful document to enhance the general care of thyroid cancer patients, I do not support ALL of the recommendations of the ATA 2006 guidelines.

    I have a number of thyroid cancer patients who have persistent thyroid cancer, demonstrated by I-131 scans, yet do not make detectable thyroglobulin (TG) despite hypothyroid withdrawal (TSH >30). In addition, Thyrogen stimulation of thyroglobulin is demonstrably less effective than hypothyroid stimulation of thyroglobulin (for example: Thyrogen may stimulate a TG to 4 in a patient, while a hypothyroid prep in the same patient raises the TG to 20). For these and other reasons, I do not support eliminating I-131 whole body scans (with TG assessments) and instead using only stimulated TG levels, unless the particular patient's tumor has already been shown to lack iodine uptake. The follow-up management of each thyroid cancer patients should be customized to the particular features of their particular situation.

    Neck ultrasound, alone, does not provide sufficient anatomical verification of disease status. I typically add metastatic bone surveys (nuclear "bone scans" do not work for thyroid cancers) and non-contrast CT scans of the lungs. If there is reason to suspect other body sites, such as the liver, an MRI with gadolinium contrast is fine (if I am still concerned to avoid iodinated CT contrast dye).

    In the typical iodine-avid thyroid cancer follow-up of a patient with negative scans and stimulated TG values, I continue to obtain scans and stimulated TG levels, although the interval between these studies grows (to a maximum of 5-yrs between hypothyroid-stimulated studies or 4-yrs between Thyrogen-stimulated studies). Some cases are not "typical".