Differentiated Thyroid Cancer - Episode 6

Identifying and Monitoring Radioiodine-Refractory DTC

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Discussion on when differentiated thyroid cancer is determined to be iodine-refractory, and how patients should be followed in this setting.


Lori Wirth, MD: Let’s talk about iodine-refractory differentiated thyroid cancer. When the thyroglobulin is going up, you search for an explanation for that rising thyroglobulin and find it. There’s a definition or a set of criteria that we use for iodine-refractory thyroid cancer. Basically, it’s when patients have known thyroid cancer that doesn’t take up radioactive iodine to begin with, or it takes up radioactive iodine and you can see it on a radioiodine scan, but the cancer grows anyway. We think of that as iodine-refractory thyroid cancer. Fortunately, in the last 10 years, we’ve made great strides in developing new therapies for iodine-refractory thyroid cancer.

I noticed the look on Jim’s face when you mentioned thyroglobulin as a tumor marker…. Everybody has access to their patient gateway or whatever we call it at our institutions. Most of my patients can’t help but look at the results of their blood tests before their visits with me. What do you do, Jim, with your thyroglobulin? Do you pay attention to it, or do you let Molly worry about it?

Jim Lesniak: We don’t worry about it, but I do look at the blood test. I look at the TSH, free T4, and thyroglobulin, and I compare it with the month before and sometimes even 1 month before that. I think about it. Fortunately, it’s been good.

Bryan McIver, MD: That idea of looking back and looking at a series of them is an important concept because the absolute level of the thyroglobulin is a little less important than the rate at which it’s changing. One thing we do in our clinic is put these results on the spreadsheet and graph them out over time. We estimate and calculate how long it takes to double, because a tumor marker like thyroglobulin doubling rapidly indicates a more rapid advanced disease and predicts into the future if we’re going to have a problem. Thyroglobulin that’s rising gradually and linearly is much less likely to become a problem and require systemic therapy. Measuring thyroglobulin, but also thinking about it like a movie rather than a snapshot, is important. Each test is a frame in that movie, but what you want to see over time is how it’s evolving and trending.

Lori Wirth, MD: You don’t want the movie to come to an end.

Molly Lesniak: Exactly.

Bryan McIver, MD: Good point.

Gary Bloom: Do you want to quickly mention antibodies, Bryan?

Bryan McIver, MD: Yes, that’s an important point. When we measure thyroglobulin, some protein circulates in the blood, and we measure that protein using an assay known as immunoassay. It depends on tracking the protein and capturing it with antibodies. Some patients have antibodies in their bloodstream that get in the way of us measuring the thyroglobulin. Whenever we measure thyroglobulin, we also measure something called the thyroglobulin antibodies. If those thyroglobulin antibodies are measurable at any level, you’re not necessarily getting an accurate reading for your thyroglobulin. You have to be aware of the falsely negative thyroglobulin of 0 when those thyroglobulin antibodies are high.

I liken it to looking at fish in a pond. If thyroglobulin antibodies muddy the water a little, then you’re probably not going to miss the big fish swimming by, but you may not see the minnows and the small fish, so early recurrence is going to be masked by the presence of those antibodies. If the antibodies are present, we’ll measure the level of those antibodies and track those over time, because antibodies that are high but falling generally indicate that the immune system is relaxing. It’s not seeing any thyroid tissue, and it’s likely that you are either in remission or don’t have progressive disease, whereas antibodies levels that are progressively rising likely indicate underlying progression of the disease. It’s not as accurate as thyroglobulin, but it’s a useful alternative.

Transcript edited for clarity.