Radioiodine Ablation

Radioactive iodine, given in either pill or liquid form, may be used to kill thyroid cells, including thyroid cancer cells. Unfortunately, there are several considerations that must be undertaken as radioactive iodine ablation does not necessarily kill all thyroid cells in all circumstances.

How radioiodine ablation works:

Follicular cells, which give rise to papillary thyroid carcinoma and follicular thyroid carcinoma, normally take up iodine from the blood. When genetic mutations occur such that a normal thyroid follicular cell becomes either a papillary or a follicular thyroid cancer, the cell’s behavior of incorporating iodine often remains intact, as this mechanism is governed by different genes from those that create cancer behavior.

As long as a particular strain of papillary or follicular thyroid carcinoma retains the behavior of incorporating iodine, detecting a relatively small cluster of thyroid cancer cells may be accomplished by giving the patient radioactive iodine, allowing it to circulate and then concentrate in thyroid cells, and then performing a diagnostic radioiodine uptake scan to look for concentrated areas of the radioactivity from the radioactive iodine.

To make iodine-avid thyroid tissue maximally avid, a patient is either allowed to become temporarily hypothyroid (which increases TSH production, stimulating thyroid cell activity) or recombinant (synthetic) TSH is given intravenously shortly before the 131-iodine is given.

Using a higher dose of radioactive iodine (and often a different isotope of iodine, 131-iodine), the radiation generated by radioactive decay can be used to deliver a lethal dose of radiation to affected cells.

Because iodine is incorporated into follicular thyroid cells and cancers derived from follicular thyroid cells (papillary and follicular thyroid carcinoma), this radiation is distributed very selectively to those cells, whether in the thyroidectomy bed, or an area of thyroid cancer spread, such as a lymph node or the lungs. Other cells that take up iodine are salivary glands, gastric mucosa, mammary glands, and choroid plexus, which means that the radioactive exposure from radioiodine is not strictly limited to cells of thyroid origin, and explains why some people experience decreased saliva production after radioiodine ablation.

The electrons emitted by the decaying radioactive 131-iodine may kill the cells that incorporated the radioactive iodine, but since these electrons travel a very short distance, the surrounding non-thyroid tissue receives virtually no radiation at all and is spared from radiation damage.

This technique works best when there is no remainder of normal thyroid cells left in the neck after thyroid surgery, because a patch of residual normal thyroid tissue can act like a sponge soaking up most of the radioactive iodine, and leaving little left to collect in any separate focus of thyroid cancer in a lymph node or other location, such as the lung. This is the reason that removing all of the thyroid gland, not just one lobe and the central isthmus, is needed before utilizing radioactive iodine as a method of scanning for residual thyroid and thyroid cancer and for killing (ablating) the residual microscopic foci of thyroid and thyroid cancer cells.

BUT…It is not possible to take a medicine and be guaranteed that all thyroid or thyroid cancer cells die.

It would be very convenient if one had only to take a dose of medicine and have the thyroid gland and all thyroid cancer die. There are two main reasons this concept does not work as one would like. First, the best medicine available for killing thyroid tissue, radioactive iodine, cannot destroy large collections of thyroid cells. Radioactive iodine does not replace the technique surgical removal of the gland because even a high dose or radioactive iodine cannot destroy an entire thyroid gland or lobe. (Sometimes radioactive iodine is used to reduce the output of an overactive thyroid in Graves disease, but this approach does not destroy all thyroid cells.) The second reason radioactive iodine is not a guaranteed way to removal all thyroid cancer cells is that some thyroid cancer cells eventually lose their ability to take in iodine. (See Loss of Avidity, below.)

The consequence of these two facts are that first, surgical removal remains the best way to remove large collections of thyroid tissue, such as a thyroid lobe or a large focus of thyroid cancer in a lymph node. Second, radioactive iodine is most useful relatively early in the lineage of a thyroid cancer—when the thyroid cancer cells still retain good ability to take in iodine. Radioiodine uptake scans are typically used to determine whether iodine avid cells are present, and if so, then radioiodine ablation may be used to try to kill these cells.

Loss of avidity

Loss of avidity to iodine may occur as a result of ongoing mutations within the cells of a thyroid cancer. This happens as a result of a fairly rapid accumulation of mutations with each generation of cell division in cancers. Eventually, one daughter cell from dividing cancer cells loses a gene necessary for uptake of iodine. That cell, and its subsequent daughter cells, therefore develop an immunity to radioactive iodine. At any given time, cancer cells that can grow and divide faster than their surrounding cells will out-compete them and become the predominant lineage. As an example, let us imagine a scenario where thyroid cancer has spread to five lymph nodes, and four of these metastases retain iodine avidity and one of these lymph node metastasis has lost this behavior. The loss of ability to take in iodine in this one metastasis would have occurred as a result of random mutations that impaired the mechanisms of taking in iodine. Now, imagine that a treatment dose of radioactive iodine is given. The four lymph node metastasis that still incorporate iodine do so and are therefore killed. But the one metastasis that does not take in iodine is unaffected by the radioiodine treatment, and it can continue to grow and even spread. When it grows and spreads through the process of cell division, each descendant cell also lacks the ability to take in iodine. As time goes on, this cell lineage (or branch of the “family tree”) flourishes with growth and spread, and is unaffected by any subsequent attempts at treatment with radioactive iodine and would not be detectable by a radioiodine scan.

When thyroid cancer cells lose iodine avidity, they often become detectable with a PET-CT.

Side effects of 131-I ablation

Radioiodine ablation commonly yields moderate side effects which primarily result from the radiation dose to salivary glands. These salivary side effects include inflammation of the salivary glands in 33.0% of cases, and 43% reported reduced salivary gland function one year after treatment. Complete lack of salivary production occurred in 4% of patients.

A decrease in white blood cell count occurred in 4% of patients. Aplastic anemia and leukemia occur in less than 2% of patients.

Temporary hair loss occurred in 23%, lasting up to 3 months.

Temporary loss of taste or smell occurred in 27%, lasting up to 3 months.

Inflammation of the eye (specifically conjunctivitis) in a chronic or recurrent fashion occurred in 28%, and 4% of patients required a procedure on the tear duct system.

14% of patients experienced an increased frequency of influenza.

Radiation precautions after treatment

Certain precautions against unintended radiation exposure to others are undertaken after a person is treated with radioiodine for ablation. The specific guidelines vary from hospital to hospital, with changes in legislation in a given area, and according to the dose of radioiodine given.

I-131 is eliminated from the body over several weeks after its administration. Most of it is eliminated in 3-5 days after tretment through natural decay and through excretion in sweat and urine. The portion of 131-I that is incorporated into thyroid hormone is lost over the ensuing weeks by natural decay and as the body processes this hormone.

Often, a patient is to stay in a hospital room for the first day or two after receiving their radioiodine. This room has lead walls and doors, preventing any transmission of radiation beyond it, and the amount of time medical staff and visitors spend in the room is generally limited. Once radioactivity has fallen sufficiently, the patient is discharged to home, and precautions to avoid accidental exposure to contacts, especially children are undertaken. These include avoiding walking barefoot, special attention to cleaning toilets, clothing, and bedsheets, and avoiding prolonged proximity within one to two meters with family members, Patients are advised not to have sexual intercourse for one month (depending on the dose used), and women are advised not to become pregnant for six months after treatment. As many airports use radiation detectors to identify smuggling of radioactive materials, patients are advised that they may trigger these detectors for up to 95 days after their treatment.