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Radioactive Iodine Therapy of thyroid cancer


Medical editor Trond Bogsrud MD
Nuclear Medicine
Oslo University Hospital

General

Nuclear medical examinations play an important part in differentiated thyroid cancer, both for therapy follow-up and for localization of local recurrence. Radioactive iodine is important for postoperative ablation, treatment of small metastases, and diffuse lung metastases. Postoperative radioactive iodine (131I ) therapy is given to patients with a high risk of recurrence after surgery. 

Examinations with radioactive iodine play a small role in the primary work-up of thyroid cancer. The diagnostic total-body scan with 200-700 MBq 131I is no longer performed before therapy, because the diagnostic dose may inhibit the subsequent uptake of the therapeutic dose (stunning), and also because a diagnostic scan has much less sensitivity for detection of remaining tissue compared to a post therapy scan. A diagnostic scan with123I can be utilized without the danger of stunning, but the medication is costly.

A diagnostic scan with131I /123 I in addition to a post-therapy scan can be taken advantageously as a SPECT/CT.

Indications

Differentiated thyroid cancer after a thyroidectomy in the presence of one of the following factors: 

  • solitary papillary thyroid carcinoma 1-2 cm in largest diameter 
  • multifocal papillary thyroid carcinoma
  • papillary cancer with metastases to regional lymph nodes
  • papillary cancer with extra thyroidal growth and vessel infiltration and with Tall cell variant
  • invasive follicular cancer with or without regional or distant metastasis 
  • minimally invasive follicular cancer > 4 cm
  • minimally invasive follicular cancer with regional or distant metastases. Generally more liberal for patients between 20-45 years and with Hûrthle cell variation. 
  • iodine-concentrating metastases
  • diffuse lung metastases

Goal

Postoperative diagnostics

  • Inspect whether there is surrounding iodine contentrating tissue concentrated in the neck, or if there is iodine-concentrating in metastases.

Postoperative radioactive iodine therapy

  • Ablation of remaining thyroid tissue to better monitor the level of s-tyroglobulin.
  • Minimize the frequency of recurrence by ablation of microscopic remains of cancer tissue.
  • Treatment for metastases.

Treatment for metastasis

  •  Ablation of metastases (iodine-concentrating)

Preparation

If an ultrasound examination for lymph node metastases in the neck has not been performed preoperatively, this must be done before diagnostics and treatment with radioactive iodine. 

Measurement of thyroglobulin (Tg) before or immediately after a thyroidectomy is preferable to have as a reference value.

All examinations and treatment with radioactive iodine should occur under TSH (thyroid stimulating hormone) stimulation. In low risk patients having an ablation dose, rhTSH can be used as an alternative to thyroxine discontinuation.

Normally, the patient must be without thyroxine for 4-5 weeks before ablation and therapy with radioactive iodine. After stopping thyroxine or a postoperative period without thyroxine, TSH must be > 30 mIE/l. The patient should not have taken triiodothyreonine in the last 10 days before testing and treatment.

It is recommended to eat a diet low in iodine for 1-2 weeks before testing and treatment.

The patient should not have an X-ray with an iodine-containing contrast agent, or take supplements high in iodine in the last two months before testing and treatment with radioactive iodine.  

The patient should fast for at least 4 hours before taking radioactive iodine orally for optimal absorption.

Other considerations

The antiarrhythmic agent, Amiodarone, can inhibit iodine uptake for six months after discontinuation.


Implementation

Patients are normally hospitalized for 2-3 days after radioactive iodine therapy.

To reduce radiation exposure to other organs, the following is recommended:

  • Copious fluid intake to frequently empty the bladder to reduce radiation exposure to the bladder/urinary tract.
  • From day two or three, the patient should suck on acidic pastilles to increase the excretion of radioactivity from saliva. Be aware that sucking on acidic pastilles already on day one leads to an increased uptake of radioactivity in saliva glands, which should be avoided.  
  • Bowel emptying in case of a post therapy scan due to high bowel uptake of radioactivity.

The more remaining iodine-concentrating tissue, the higher the likelihood of radiation-induced thyroiditis, causing tenderness and discomfort in the neck.

Thyroid scintigraphy and iodine uptake testing after total thyroidectomy

3 MBq 131I  has sufficient activity for imaging (and possible uptake measurement) to determine the amount of remaining tissue before ablation. Imaging and uptake testing can take place as early as four hours after the dosage is given, even if 24 hours is more optimal, and sometimes necessary, for a satisfactory image and uptake.

A negative scan after four hours may be due to delayed uptake, small amount of or poor uptake by remaining tissue, and does not indicate an absence of remaining tissue. Repeated image and uptake testing 20-24 hours after uptake must be performed. With a negative scan after 24 hours without a known iodine exposure, the amount of iodine in urine should be measured. The most common cause is that the patient has recently had an X-ray with an iodine-containing contrast agent.

Even with Tg < 0.2 μg/l, small remains of normal gland tissue can be found in the throat.

Diffuse lung metastases can be detected even with iodine activity as low as 3 MBq.

Postoperative radioactive iodine therapy

Activity

  • In low risk patients without suspicion of lymph node metastases, standard activity (3.7 GBq) is used.
  • In patients at higher risk for metastases and remaining localized disease, as well as iodine-concentrating metastases, higher activity is used (4.5-8 GBq).

Radioactive iodine therapy for metastases

Radioactive iodine therapy for metastases is given only when the metastases are concentrating iodine, and preferably only for small metastases with high uptake. 

  • The treatment effect is very good for diffuse microscopic lung metastases with high uptake ("black lungs" on scintigraphy). 
  • Bone metastases will often respond poorly to treatment with radioactive iodine despite high uptake.
  • With a raised Tg, but where the preceding post therapy scan was negative, repeated treatment with radioactive iodine is given if Tg showed a significant increase after preceding therapy (seen rarely). 

Optimization with endogenous TSH stimulation and a diet low in iodine is important.

Patients with metastases are treated with higher activity (6-8 GBq) than ablation of low risk patients.

Radioactive iodine therapy is of little therapeutic value for large metastases with low iodine uptake.

 


Follow-up

The patient can be discharged when the dosage rate measured 1 m from the patient is < 30 µSv/hour. The age and dosage to which the patients' family/friends are exposed is more important than the dosage rate.

Postoperative radioactive iodine therapy

A post therapy scan can be completed 3-5 days after intake of the ablation dose. 

Thyroxine is started on the third day after intake of radioactive iodine.

Triiodothyronine is given for 10 days in addition to thyroxine to patients under 60 years without a known problem of chronic or paroxycystic atrial fibrillation. 

Side effects

Acute radiation induced thyroiditis in remaining tissue will cause tenderness, swelling, and discomfort in the throat starting 6-8 hours after the treatment dose (duration 3-5 days). It is important to inform the patient that this does not pose a threat of airway obstruction.

Acute radiation induced gastritis with nausea and pain starting 6-8 hours after the treatment dose lasting for 3-5 days is normal.

Reduced/change in sense of smell sometimes occurs and may last up to 6 months.

Reduction of saliva secretion occurs and can be permanent after an activity accumulation >10GBq.

Follow-up examination and possibly new ablation therapy

The patient should have a follow-up examination normally 6-8 months after postoperative ablation (at least 4 months).

Suppression therapy for follicular and papillary thyroid carcinoma

Three days after treatment with radioactive iodine, the patient will start thyroid hormone treatment. The starting dosage is 125-150 µg, or the same dose as the thyroxine sodium (Levaxin®) before treatment. In addition,10-20 µg triiodothyronine is given 2-3 times daily for 1-2 weeks (caution in elderly and heart disease patients).


Background

Mechanism for Radioactive Iodine Therapy

Cancer developing from follicular thyroid cells are often highly differentiated carcinomas. The cancer cells maintain specific functions such as thyroglobulin production and the ability to take up iodine. The absorption of iodine by cancer cells delivers the radiation right to the target. This is taken advantage of in postoperative diagnostics and treatment.

Normal thyrocytes take up iodine via NIS (sodium-iodide symporter) and protein bind to thryoglobulin which is stored in the follicle lumen. In a euthyreoid person, 22% of the radioactive iodine test dose can be found in the thyroid after 24 hours.  

The uptake in thyroid cancer cells depends on the grade of differentiation. It is assumed that uptake of thyroid cancer cells may be around 100 times less than in normal thyroid cells. Follicular cancer has a higher uptake than papillary cancer.


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