By Alon Kahana, MD, PhD (University of Michigan)

Today’s blog will discuss the basics of Graves disease and thyroid eye disease. This most likely will be the first in a series of blogs on this really important and complex topic, and will focus on the treatment of the endocrine disorder itself.

I frequently get sent patients who are hyperthyroid and wondering which of their treatment options should be chosen for their care. Some are still hyperthyroid, with suppressed TSH and elevated free T4 in lab tests. Others have been on methimazole and have adequate function but the methimazole has been used for many months, and sometimes years, and the time has come to decide a definitive treatment. Some have unstable thyroid hormone levels while on methimazole, and their doctors struggle to stabilize the disease.

I should start by stating that this topic is somewhat controversial. It’s amazing that with all we know about this disease that even the most basic topic is controversial, but the same reason why an eye surgeon is asked to comment on endocrine treatment is also the reason why it is controversial, namely the thyroid eye disease. The two key options for definitive treatment are radioactive iodine, and surgical thyroidectomy. Radioactive iodine uses the fact that the thyroid gland accumulates iodine preferentially to hit the body with radioactive iodine that gets accumulated in the thyroid gland and literally blows up the thyroid gland from the radioactive energy. This technique is quite effective at damaging the thyroid gland. But it requires some nimble predictive powers. Based on pretreatment scans and various calculations by the nuclear medicine specialist, the correct dosage is predicted. This usually works as planned but many times it does not, even in the best of hands, leading to an incompletely treated thyroid gland and fluctuating thyroid hormone levels. Sometimes the thyroid gland requires a second treatment, which has its own unique complication rates. Radioactive iodine also puts at risk young people because the radioactivity carries with it a small risk of cancer. And the bone marrow also has some iodine, and therefore treatment with radioactive iodine also causes the bone marrow to take a hit. Therefore, the treatment with radioactive iodine is not completely benign.

Furthermore, radioactive iodine has been known for many decades to be associated with worsening eye disease. The reasons are not clearly known, primarily because we still do not know the cause of thyroid eye disease. However, radioactive iodine treatment of an enlarged hyperactive thyroid gland is known to cause sudden release of thyroid hormone as well as all the antigens in the thyroid gland against which the autoimmune antibodies form. Therefore, you end up with a situation in which the endocrine function becomes more acute, and the autoimmune function issues become potentially more acute. It can take weeks for the thyroid hormone levels to normalize, and it can take months to a year or even longer for the antibody situation to normalize. So it is not surprising that the general autoimmune process is worsened by the acute treatment with radioactivity of the thyroid gland.

Now the effects of the thyroid treatment with radioactive iodine can be somewhat mitigated by systemic steroids. Taken starting just before treatment and extended over three to four weeks. The effects on the eyes can also be reduced if the patient does not smoke. It is worth mentioning that smoking is one of the most important risk factors for developing severe thyroid eye disease, and will be a topic for discussion at a future blog.

So if radioactive iodine has a risk of cancer, a risk of increasing the thyroid eye disease, and a prolonged phase of thyroid hormone instability, why is it such a popular treatment option? The answer is because it works without an incision and without a prolonged period of convalescence, allowing the patient to return to normal activities within a couple days of treatment, and it usually works quite well with minimal repercussions in the typical patient who follows doctor’s orders, does not smoke, takes their medications on time, and goes to follow ups on time. What is the alternative to radioactive iodine you might ask? The main one is surgical thyroidectomy, and that will be the topic for the next blog. I will close by stating that while radioactive iodine with thyroid hormone replacement is a good option for the treatment of Graves’ disease, in my opinion long term use of methimazole is not a good option. The methimazole simply masks the autoimmune process, while subjecting the liver to potentially irreversible damage. Some people seem to believe that there are significant rates of remission in the context of using methimazole. My own experience does not bear this out. Some patients will go into a quiescent phase of their disease, and this may last for a few months. In some papers in the literature, this has been referred to as remission. However, this is not remission but just quiescence, with flare-ups virtually inevitable. In my experience it is the unusual patient who enters true remission that is long lasting, meaning several years.