The mechanism of how RAI Treatment works to treat thyroid cancer was not discovered until years following its use to treat papillary thyroid cancers. We now know today that papillary thyroid cancers can possess a type of key hole on the surface of their cell called a symporter that allows iodine to be taken into the cell. Under normal circumstances, iodine is taken up by normal thyroid cells in the process of producing the body’s thyroid hormone. Although papillary thyroid cancer rarely produces thyroid hormone itself, it frequently maintains this iodine symporter and ability to take up iodine. In the treatment of papillary thyroid cancer, this can be taken advantage of by having the patient swallow an iodine pill that has been radioactively charged.

The papillary thyroid cancer patient swallows a radioactive iodine form of iodine called iodine 131 (I-131) in a liquid or pill (capsule) form. The RAI is absorbed through digestion and circulated throughout the body in bloodstream. Papillary thyroid cancer cells can pick up the radioactive iodine (if the possess the symporter for iodine) wherever they are located in the body. Once taken into the papillary thyroid cancer cells, the radioactive iodine delivers a local radiation treatment in the area where the iodine is concentrated.

The papillary thyroid cancer diagnosis, itself, is not an indication for RAI treatment. If you had a papillary thyroid cancer, 25 years ago, you would have almost certainly been treated with surgery and RAI. Today, only approximately 20% of all papillary thyroid cancer patients undergo post-0perative RAI treatment. RAI treatment is primarily beneficial only when the patient has undergone a total thyroidectomy (complete removal of the thyroid gland) in the surgery for their papillary thyroid cancer. RAI treatment or therapy should only be used in instances where the risk of the papillary thyroid cancer coming back is greater than the potential risks of RAI therapy itself. There is no urgency to rush into treatment with RAI. RAI can be given as early as 4-5 weeks following total thyroidectomy but can be delayed for months or even years following surgery. The papillary thyroid cancer must have the symporter for iodine and take up iodine to be effective. Papillary thyroid cancers that take up iodine are called iodine avid. Importantly, the ability of a papillary thyroid cancer to take up iodine is required for RAI therapy to work but is not an indication for therapy. What this means is that just because a papillary thyroid can be treated with RAI is not a reason to use RAI.

Papillary thyroid cancer should only undergo RAI treatment (therapy) in instances where the risk of the papillary thyroid cancer coming back is greater than the potential risks of RAI therapy itself. In papillary thyroid cancer treatment, there is no urgency for the rapid delivery of RAI. RAI can be given as early as 4-5 weeks following total thyroidectomy but can be delayed for months or even years following surgery.

Papillary thyroid cancer indications for RAI treatment include:
  • Papillary thyroid cancer evidence of invasion (or extension) outside of the thyroid gland capsule (called soft tissue extension)
  • Papillary thyroid cancer that has spread to at least two lymph nodes in the neck (in any area of the neck)
  • The papillary thyroid cancer team desire to destroy any additional thyroid tissue (which is producing thyroglobulin)
  • Papillary thyroid cancer that has spread to distant sites (lungs, bones, and liver)
  • The papillary thyroid cancer takes up the iodine

Preparation of a Papillary Thyroid Cancer Patient for Radioactive Iodine Treatment

Papillary thyroid cancer patients must be taken off of levothyroxine thyroid hormone (T4 hormone) for a minimum of four weeks, taken off of liothyrionine thyroid hormone (T3 hormone) for a minimum of two weeks, or receive a medication which is TSH (which is a pharmaceutical production of the Thyroid Stimulating Hormone [TSH] produced as a recombinant protein which is identical to the TSH normally produced by the pituitary gland). Additionally, papillary thyroid cancer patients must be on a low iodine diet for a minimum of four weeks to starve their body of iodine. Those patients which have undergone CAT scans with intravenous contrast must wait until their blood iodine levels have been adequately decreased (usually at least two months). Note, a desire to treat with radioactive iodine should never prevent the use of necessary CAT scans for the evaluation of a papillary thyroid cancer patient.

The potential risks of RAI treatment include:

  • Dry mouth and or eyes
  • Narrowing of the drainage duct of the eye’s tears leading to excessive tearing down the cheek
  • Decreased production of blood cells by the bone marrow (with very high RAI doses)
  • Swelling in your cheeks from inflammation or damage to the saliva producing glands (the spit glands)
  • Short term changes to taste and smell (usually resolve in 4-8 weeks)
  • Lowered testosterone levels in males (usually resolves within the first year)
  • Change in periods (menstruation) in women (usually resolves within the first year)
  • Second tumors (these are rare and can be discussed with your thyroid cancer treatment team)

Papillary Thyroid Cancer Treatment With RAI (Radioactive Iodine): How and How Much Treatment?

Papillary thyroid cancer guidelines for post operative treatment with radioactive iodine were last updated in the American Thyroid Association 2015 edition. Some endocrinologists and nuclear medicine specialists order a preliminary nuclear study called a thyroid cancer uptake study. After your doctor has prepared your body for RAI by either stopping your use of thyroid hormone pills or giving injections of recombinant TSH (Thyrogen), they may choose to give you a small dose of RAI and perform a special nuclear scan called a Thyroid Cancer Uptake Study. This is a very low quantity of radioactive iodine and may be I131 or I123. In most cases, it is done the day before the higher dose RAI treatment.

There are several potential benefits in obtaining a Thyroid Cancer Uptake Study:

      1. The papillary thyroid cancer’s ability to produce the blood marker thyroglobulin is determined while the patient is in a hypothyroid state (or given Thyrogen). This is called a stimulated thyroglobulin level.
      2. Where the papillary thyroid cancer exists in the body and how much of the swallowed dose or radioactive iodine is taken up by the cancer is able to be determined by the nuclear scan.
      3. The thyroid cancer uptake study can be utilized to determine the optimal dose of the radioactive iodine treatment the following day.

In a papillary thyroid cancer uptake scan, the image will determine if there is any evidence of iodine uptake in the body. Approximately 90% of patients will have some uptake of iodine following a total thyroidectomy. Papillary thyroid cancer is not the only reason that iodine can be taken up by tissue. One such issue is retained thyroid tissue. How much retained thyroid tissue is related to the thoroughness of your thyroid surgeon in performing a total thyroidectomy. The amount of RAI chosen to treat the papillary thyroid cancer is based upon:

  • The level of thyroglobulin while the TSH is elevated for the scan (this is called a stimulated thyroglobulin)
  • The percent uptake of RAI in the Thyroid Cancer Uptake Scan
  • The papillary thyroid cancer locations of disease (uptake)
  • Prior RAI treatment doses

Some argue against obtaining Thyroid Cancer Uptake Studies because:

      1. Low dose of RAI may not detect minimal microscopic disease and therefore RAI treatment not be given to the patient if no uptake is seen on the initial study.
      2. There is a theory called “stunning” where it is suggested that low dose of RAI during the thyroid cancer uptake study may be taken up by papillary thyroid cancer and will result in "stunning" but not killing of thyroid cancer cells, making the high dose of radioactive iodine less effective. Studies however have suggested that this does not actually occur.
      3. Higher doses of RAI may show smaller disease that may not have been visualized on a low dose thyroid cancer uptake study.

As an alternative to a thyroid cancer uptake study of a small dose of RAI, some doctors may choose to give you their prescribed dose of RAI as a definitive treatment. Following either of the above approaches to treat a papillary thyroid cancer with RAI, a scan is obtained following the therapeutic dose in 48 to 72 hours to determine the location and percent uptake of the radioactive iodine. The strength of radioactive iodine is described in millicuries. The papillary thyroid cancer treatment dose of radioactive iodine ranges from about 30 millicuries to approximately 150 millicuries. Low risk papillary thyroid cancers and eradication of small amounts of retained thyroid tissue are treated with lower doses of RAI in the 30-50 range. Intermediate risk papillary thyroid cancers such as patients above 50 years of age with lymph node spread are treated in the middle ranges. Papillary thyroid cancers with high risk features or distant spread of disease are treated with higher doses in the 150 millicurie range.

Papillary thyroid cancers can also be treated with radioactive iodine based upon a method called dosimetry. This is a radiation physics determination utilizing complex mathematical methods to determine the actual dose of radiation that will be delivered to a particular area of papillary thyroid cancer. In some circumstances, dosimetry can allow much higher doses of radioactive iodine to be prescribed when papillary thyroid cancers effectively take up the treatment. Papillary thyroid cancers, however, rarely require dosimetry for definitive treatment.

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