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Treatment of thyroid cancer

Radioactive iodine scan showing neck uptake due to normal thyroid and, below this, massive and diffuse uptake in both lungs due to very avid iodine uptake by diffuse lung metastases from thyroid cancer.

In patients with differentiated thyroid cancer, radical surgery (thyroidectomy) involving the total removal of the thyroid gland is advocated in most cases.


Several points need to be made. The first is that a radical thyroidectomy is rarely complete, as the surgeon has to preserve the parathyroid glands that subserve the body’s calcium homeostasis and live within the confines of the thyroid capsular compartment; (these are different from the C cells that are an integral part of the thyroid itself). Furthermore, the surgeon has to preserve the nerves to the larynx which run through the thyroid compartment.

In order to preserve both these structures, the surgeon is almost never able to safely remove the last normal thyroid cells. This is of importance as residual thyroid tissue remains and will show up on subsequent radio-iodine tracer scans and confuse the doctors; the residual thyroid tissue will also lead to a measurable thyroglobulin in the blood, again confusing the doctors. These facts provide the important reason for the radiodine ablation dose -vide infra


The second main point to make is that, in differentiated thyroid cancer, radical thyroidectomy may still be indicated even when there is metastatic carcinoma because it will only be possible to target high doses of radioiodine onto the tumour cells when the higher avidity normal thyroid tissue has been ablated, and the simplest way of achieving a debulking of the normal thyroid is to take it out surgically.


These principles do not apply to anaplastic (undifferentiated) carcinoma, to medullary thyroid carcinoma or lymphoma of the thyroid.


Following radical thyroidectomy, and in patients with differentiated thyroid carcinoma, there follows an ‘ablation dose’ of radioiodine which is specifically aimed at obliterating the normal thyroid remnant (and taking advantage of the fact that the normal thyroid cell residuum is highly avid for up taking the radioactive isotope of iodine). There is no point in such radioiodine ablation in the other types of thyroid carcinoma.


For the radioiodine ablation dose, the patient is admitted to a specially designated hospital side room where, in solitary confinement for 2-3 days, the patient remains after swallowing the radioiodine capsule. The radioiodine decays with a half life of 8 days and is excreted in the urine (but also in saliva and other body secretions) hence the solitary confinement whilst the radioactivity is high.


 Female patients must not be pregnant and all patients must remain in the room until their whole body radiation dose is below acceptable and legal limits. After discharge, the patient must avoid close contact with children or pregnant women or travel by air flights (where they may be seated next to such individuals) for two weeks. These facts worry some patients but they may be re-assured that these precautions are just exceeding safe precautions and the patient is not discharged until the legal limits on dose have been measured and are acceptable for normal circulation in the adult population. The risk for the patient himself/herself is minimal.


Following radical thyroidectomy for any thyroid carcinoma (of whatever subtype), the patient is placed on thyroid hormone replacement, necessarily because the normal thyroid tissue has been removed. In the case of differentiated thyroid cancer (papillary and follicular variants) the dose of thyroid hormone replacement is high enough to fully suppress the pituitary TSH (the hormone from the pituitary that controls thyroid secretion, but which can act as a growth promoter for differentiated thyroid cancer); for the other forms of thyroid cancer in where surgery is performed, notably medullary thyroid cancer (the replacement dose is just kept in the normal range).


In differentiated thyroid cancer, the short acting thyroid hormone (liothyronine or T3) is usually prescribed initially, as the doctor will need to render the patient underactive at his follow-up check points (vide infra) and this is more quickly and easily achieved with a patient on T3.


Later, the patient will be converted to T4 (thyroxine) which is longer acting and the optimal dose of each is monitored by serum testing - the ideal is one that renders the serum T3 in the normal range and suppresses the serum level of the pituitary TSH hormone (demonstrating that there is no pituitary drive to thyroid tissue, which could theoretically include differentiated thyroid cancer cells).


Where there is no evidence of thyroid carcinoma outside the thyroid gland, the patients with differentiated thyroid carcinoma (papillary and follicular) are thereafter carefully monitored by clinical examinations and two other more specific tests. The first is the radioiodine tracer scan where a tiny dose of a radioiodine isotope is administered (usually orally) and then a whole body scinitiscan is performed to see if there is any iodine avid tissue remaining (which there should not be in a patient who has had a radical thyroidectomy and a radioiodine ablation of the normal post-surgical remnant).


The second specific test is a serum marker test and relies on the fact that there is a specific thyroid protein molecule that is secreted into the blood by normal and differentiated thyroid cancer cells; it is called ‘thyroglobulin’.


Some doctors will not always ablate the thyroid remnant with radioiodine after the operation (for example in low risk patients, e.g. the young women of less than thirty five years with an intrathyroidal papillary cancer) and just place the patients on TSH suppressive of thyroxine. They will monitor the thyroglobulin in follow-up whilst the patient is on thyroxine (T4); this may be acceptable practice in low risk patients but if these patients do subsequently relapse then it is necessary to ablate the thyroid normal remnant before the iodine therapy programme can get at the metastatic cells.


In a patient who has differentiated thyroid cancer and has undergone radical thyroidectomy and a radioactive ablation dose to eradicate the post-surgical remnant, there is a radioactive iodine whole body scan performed at three months post ablation and a further one six months later. If both these are negative for iodine up taking tissue and if the serum thyroglobulin is undetectable at these check points, then the patient is regarded as being without cancer and is thereafter followed by serial thyroglobulin levels and clinical examinations only. Should anything suspicious arise clinically (e.g. a node appear in the neck or a shadow on the chest x-ray) or a rise in the serum thyroglobulin occur, then the patient will have another radioiodine whole body scan performed at that time.


It should be noted that both serum thyroglobulin measurements and the whole body radioiodine whole body scans are more sensitive measures when the patient has a high circulating serum TSH.


At the time of the radioiodine tracer scans, the patient is taken off thyroid hormone therapy which leads to an elevation in the TSH (vide supra) and creates the best conditions for radioactive iodine uptake by any iodine avid tissue (and increases any thyroglobulin in the blood, thus also helping increasing the sensitivity of this serum marker for diagnosing relapse of the cancer). It is easiest to engender this high TSH state when the patient has been on T3 as it only requires 8 days off T3 for the TSH to become high. If the patient cannot come off thyrpoid hormone for any reason, it is possible to create the high TSH state required by giving intramuscular injections of genetically engineered human TSH for two days before the scan. This produces (artificially) high TSH in the blood and is an (expensive) alternative to withdrawing the patient off T3.


Where there is metastatic differentiated thyroid cancer and it is proven to be iodine avid on the radioiodine whole body tracer scans, then the doctor will proceed to radioiodine therapy once the normal thyroid remnant has been ablated.


The doses of radioactive iodine are repeated (often at six month intervals) until the iodine avid, metastatic disease disappears on imaging and stops up taking any more iodine and the serum thyroglobulin becomes undetectable. In the figure above, there is shown a radioactive iodine scan performed on a patient who has disease in the neck (the small black blobs X2 at the top of the figure) and widespread uptake throughout both lungs (the two larger triangular black areas below and to either side of the figure). This patient has very iodine avid thyroid cancer that is recurrent in the neck and both lungs and underwent a successful course of multiple radio-active iodine therapy doses which achieved complete remission of the disease.


The adroit use of radioactive iodine therapy in this disease is most important to long term survival in patients who have disease outside the gland.


Where the thyroid cancer is locally invasive in the neck (e.g. it is infiltrating the muscles of the neck adjacent to the thyroid or is invading the larynx) then it is advisable to recommend a course of radiotherapy to the neck and this takes place in the post-operative period in addition to the radioactive ablation therapy.


Where the patient with differentiated thyroid cancer relapses in the neck lymph nodes only, then it is advisable to remove the affected lymph nodes prior to the radioactive iodine programme. When the disease is further afield (e.g. metastatic to lungs or bones) then surgery is obviously not appropriate and the therapy relies entirely on the radioactive iodine isotope therapy.


For all patients in between radioiodine therapy doses and long-term, the patient remains on thyroid hormone in generous dosage to ensure that the serum TSH remains fully suppressed.



For patients with undifferentiated/anaplastic thyroid cancer, the use of radical thyroidectomy is confined to those patients who have localised disease to the thyroid gland at presentation to the doctor. This is the minority of cases and most patients are recommended to receive radiotherapy to the neck as this disease is usually locally invasive at the time of presentation and tends to invade adjacent neck tissues and may throttle the patient if its progress in the neck is not stopped. High dose radiotherapy is usually the treatment offered to retard progress of the disease in the neck. Chemotherapy does not have a good track record in retarding the progress of undifferentiated thyroid cancer.


Medullary thyroid cancer patients are recommended to receive radical thyroidectomy if the disease is localised to the thyroid gland and the operation usually includes the central neck nodes of the neck.


Post-operative radiotherapy is delivered if the diseaes is invasive into other neck tissues.


If the operation is successful, then the serum calcitonin will fall to the normal range.


Where the disease has spread or relapsed (raised serum marker: calcitonin), then the use of isotopes of MIBG (a chemical that is specifically taken up by the medullary cancer cells in some cases) or octreotide can be introduced in high radioactively labelled dosage to deliver a radiation dose to the relapsed cancer in a comparable way to iodine-131 therapy in differentiated thyroid cancer. Orthodox chemotherapy does not have a good track record in retarding the progress of the disease.


Localised thyroid lymphoma is treated by a combination of chemotherapy (usually a short course of some three months) followed by a course of radiotherapy to the neck and upper chest (the next port of call = spread) of this lymphoma; the radiotherapy course usually lasts for four weeks and causes some tiredness and temporary difficulty in swallowing and skin soreness over the area. When the disease has spread further afield, then total reliance is on an aggressive chemotherapy programme (see lymphoma section). For localised MALT lymphoma, radiotherapy alone may suffice, as the chance of spread is less than with higher grade lymphomas.

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