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Radioactive Iodine (RAI) Treatment for Hurthle cell cancer

The “magic bullet” to treat cancer has eluded cancer specialists since the first days of oncology. The concept of a targeted therapy is exquisitely popular today but is not new. Radioactive iodine treatment for hurthle cell cancer was, in fact, one of the first real targeted therapies ever to be developed for any cancer. The mechanism of how it works to treat thyroid cancer was not discovered until years following its use to treat thyroid cancers. We now know today that hurthle cell 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 hurthle cell cancer rarely produces any significant amounts of thyroid hormone itself, it frequently maintains this iodine symporter and ability to take up iodine. In the treatment of hurthle cell cancer, this can be taken advantage of by having the patient swallow an iodine pill that has been radioactively charged. Hurthle cell cancer, historically, is not highly responsive to radioactive iodine therapy. However, it still remains a mainstay of treatment today. Indications for treatment with radioactive iodine for hurthle cell cancers include whether the cancer has grown into blood vessels, spread outside of the thyroid gland itself or spread into the lymph nodes of the neck or distant sites in the body. Although radioactive iodine is used commonplace in the treatment of hurhtle cell cancer, its effectiveness is frequently questioned. Last updated January 11, 2022

The hurthle cell 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. Hurthle cell cancer cells can pick up the radioactive iodine (if they possess the symporter for iodine) wherever they are located in the body. Once taken into the hurthle cell cancer cells, the radioactive iodine delivers a local radiation treatment in the area where the iodine is concentrated.

The hurthle cell cancer diagnosis, itself, is not an indication for RAI treatment. If you had a hurthle cell cancer, 25 years ago, you would have almost certainly been treated with surgery and RAI. Today, approximately 50% of all hurthle cell cancer patients undergo post-operative 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 hurthle cell cancer. You can see a video of a Total Thyroidectomy performed here - IMPORTANT NOTE this is a real video of an operation in progress, if you are not comfortable seeing the important anatomic structures found during an operation then please do not click!

RAI treatment or therapy should only be used in instances where the risk of the hurthle cell 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 hurthle cell cancer must have the symporter for iodine and take up iodine to be effective. Hurthle cell cancers that take up iodine are called iodine avid. Importantly, the ability of a hurthle cell 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 hurthle cell cancer can be treated with RAI is not a reason to use RAI. Clear evidence for the benefit of radioactive iodine in hurthle cell cancer is, in fact, quite lacking when critically analyzing Zimmerman's 2015 review of the literature in the journal Thyroid Research.

Hurthle cell cancer indications for RAI treatment include:
  • Hurthle cell cancer evidence of invasion (or extension) outside of the thyroid gland capsule (called soft tissue extension)
  • Any hurthle cell cancer that has spread to a lymph node in the neck (in any area of the neck)
  • The hurthle cell cancer team desire to destroy any additional thyroid tissue (which is producing thyroglobulin)
  • Hurthle cell cancer that has spread to distant sites (lungs, bones, and liver)
  • Editors note: The above are indications however the hurthle cell cancer must be able to take up the iodine!!
Hurthle cell cancer and neoplasms without indication for RAI treatment include:
  • Hurthle cell neoplasm of uncertain malignant potential
  • Hurthle cell cancer (carcinoma) of uncertain malignant potential
  • Hurthle cell cancer (carcinoma) with thickened capsule
  • Hurthle cell cancer with microinvasion of capsule

Preparation of a Hurthle cell cancer Patient for Radioactive Iodine Treatment

Hurthle cell 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, hurthle cell 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 hurthle cell 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)

Hurthle Cell Cancer Treatment With RAI (Radioactive Iodine): How and How Much Treatment?

Hurthle cell 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:

  • The hurthle cell 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. When your thyroid hormone levels are very very low, your TSH level is highest. This gives the thyroid cancer team a good “feel” for whether you have any disease whatsoever and the likelihood for cure.
  • Where the hurthle cell 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.
  • The thyroid cancer uptake study can be utilized to determine the optimal dose of the radioactive iodine treatment the following day.

In a hurthle cell cancer uptake scan, the images determine if there is any evidence of iodine uptake in the body. Hurthle cell cancer is not the only reason that iodine can be taken up by tissue. One such issue is retained thyroid tissue. Approximately 90% of patients will have some uptake of iodine following a total thyroidectomy within the surgical site! This is largely expected. Just not a lot of uptake. In most cases it should be a fraction of a percent around 0.2% or less of the taken dose of radioactive iodine. How much retained thyroid tissue is related to the thoroughness of your thyroid surgeon in performing a total thyroidectomy! You are in control here. Make sure you choose an expert thyroid cancer surgeon. - watch this video on finding an expert surgeon. The amount of RAI chosen to treat the hurthle cell cancer is based upon this uptake. In some patients, the nerves of the voice box may actually travel through thyroid tissue and therefore in protecting the voice box nerves, some thyroid tissue must be retained. In such circumstances, iodine uptake will be expected to be identified in these patients.:

  • 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 hurthle cell cancer locations of disease (uptake)
  • Prior RAI treatment doses

Some argue against obtaining Thyroid Cancer Uptake Studies because:

  • Low dose of RAI may not detect minimal microscopic disease and therefore RAI treatment should not be given to the patient if no uptake is seen on the initial study.
  • 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 hurthle cell 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.
  • 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 hurthle cell 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 hurthle cell cancer treatment dose of radioactive iodine ranges from about 30 millicuries to approximately 150 millicuries. Low risk hurthle cell cancers and eradication of small amounts of retained thyroid tissue are treated with lower doses of RAI in the 30-50 range. Intermediate risk hurthle cell cancers such as patients above 50 years of age with lymph node spread are treated in the middle ranges. Hurthle cell cancers with high risk features (such as soft tissue extension and widely spreading into blood vessels or soft tissue, or angry looking cells= poorly differentiated) or distant spread of disease in the body are treated with higher doses in the 150 millicurie range. There is evidence now that radiaacitve iodine will benefit you if your Hurthle cell cancer has spread to lymph nodes, invaded blood vessels or soft tissue. (Thyroid. 2016 Jul;26(7):959-64. doi: 10.1089/thy.2016.0246. Epub 2016 Jun 6. Thyroid. 2016 Jul;26(7):959-64. doi: 10.1089/thy.2016.0246. Epub 2016 Jun 6. Radioactive Iodine Treatment Is Associated with Improved Survival for Patients with Hürthle Cell Carcinoma.)

Hurthle cell 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 hurthle cell cancer. In some circumstances, dosimetry can allow much higher doses of radioactive iodine to be prescribed when hurthle cell cancers effectively take up the treatment. Hurthle cell cancers, however, rarely require dosimetry for definitive treatment.