Controversies in Thyrotoxicosis Treatment

I am Kristien Boelaert. I am a consultant endocrinologist from the Queen Elizabeth Hospital in Birmingham and a reader in endocrinology at the University of Birmingham. My research focuses on the management of patients with thyroid dysfunction as well as thyroid nodules and thyroid cancer.

I was asked to give a talk at the 2017 Endocrine Society Annual Meeting to provide an outside view^[1] of the new 2016 American Thyroid Association (ATA) guidelines^[2] on the management of patients with thyrotoxicosis. I used a case-based format because often, there is not real agreement on how best to manage patients, and I wanted to highlight some new paradigms that were brought out by these guidelines.

Case 1: Establishing Etiology

For the first case, I wanted to highlight the importance of establishing the etiology of thyrotoxicosis. In the United States and the United Kingdom, the most common reason for having thyrotoxicosis is hyperthyroidism from Graves disease, a condition caused by antibodies to the thyroid gland.

The second most common cause is toxic nodular hyperthyroidism, which is more common in areas with iodine deficiency.

Treatments of Graves disease and toxic nodular hyperthyroidism are different: Antithyroid drugs may be effective for Graves disease but are not so effective for toxic nodular hyperthyroidism.

In order to establish the diagnosis, the guidelines recommend that we measure thyroid-stimulating hormone (TSH) receptor antibodies (the causative problem in Graves disease), do radioactive iodine uptake, or do an ultrasound scan. I generally measure TSH receptor antibodies, and if these are not raised, I do further scanning to establish whether toxic nodular hyperthyroidism is present.

Case 2: When to Stop Antithyroid Agents?

The second case I discussed was to highlight new guidance that has changed my practice.

When patients have undergone a prolonged course of treatment with antithyroid drugs, it can be difficult to decide exactly when to stop. The evidence shows that a 12- to 18-month course is generally long enough to be effective and that extending it for longer than 18 months does not really make a difference to outcomes.

The new guidance, based on quite nice evidence, suggests that we should remeasure TSH receptor antibodies before deciding whether to stop antithyroid drugs. I gauged opinion from the audience as to who does this; it is indeed something that I have now incorporated in my practice.

Case 3: Radioactive Iodine

The third case was to highlight treatment of thyrotoxicosis with radioactive iodine. The patient case I used was that of a smoker.

There is no real agreement as to what we should do with smokers, because we know that they have an increased risk of developing Graves orbitopathy. This condition that can be quite debilitating and is caused by the antibodies that cause Graves disease.

Currently, the guidelines do not recommend that we treat all smokers with steroids before or around the time of radioactive iodine. Certainly, that is not something I do. Quite a few people in the audience, however, would have given steroids because the patient was a smoker but did not really have any clinical signs of orbitopathy.

This case also highlighted the question of whether we should pretreat this patient with antithyroid drugs before giving radioactive iodine. For many years in my practice, we generally treated patients with antithyroid drugs, rendering them euthyroid before proceeding with radioactive iodine so they did not feel unwell after treatment. I showed data demonstrating that thyroid hormone levels will rise after the treatment with radioactive iodine.^[3] This can be debilitating and, in patients with other comorbidities, can result in significant complications.

There is evidence in the literature that treatment with antithyroid drugs before and after radioactive iodine actually results in induction of a degree of radioactive iodine resistance.^[4]

Practice varies in different countries; I will certainly pretreat patients with antithyroid drugs in my practice.

Case 4: Preparing for Thyroidectomy

The fourth case was used to discuss new guidance on how to prepare patients undergoing a thyroidectomy, which is the third treatment option for patients with hyperthyroidism. There was a fairly general consensus that patients need a beta-blocker and treatment with potassium iodide. Potassium iodide treatment is not something I have routinely used, but I am now incorporating it in my practice.

Further treatment with such things as steroids and cholestyramine are not required; they may have a role in an emergency thyroidectomy, but not in routine thyroidectomy. It is important to remember that patients need to be rendered euthyroid with antithyroid drugs before we proceed with a thyroidectomy, and that we also need to establish their calcium and vitamin D status.

Case 5: Management of Subclinical Hyperthyroidism

The fifth case focused on what remains a very controversial area in thyroid disease: management of subclinical hyperthyroidism. The patient described was not quite 65 years old and had repeated undetectable serum TSH, with normal serum free thyroxine (T₄) and free triiodothyronine (T₃) concentrations and negative TSH receptor antibodies. It is important that we evaluate these patients with an uptake scan and that we treat them if there is evidence of toxic nodular disease.

There remains controversy about what we should do with patients who do not have a consistently undetectable serum TSH. I would not treat most of those patients unless there are significant comorbidities, such as cardiovascular disease or osteoporosis, or if the patient is highly symptomatic.

Summary

The guidelines suggest that when a patient presents with thyrotoxicosis, we should have a full discussion of the various treatment options with their advantages and disadvantages.

We work in an environment of patient-centered medicine, and it is really important that treatment is individualized. There are regional preferences for certain treatment options, so treatment is also dependent on resources in your area.

Treatment should be right for that patient. Often, there is not a right or wrong decision, but a right or wrong decision for that particular patient in that particular situation.

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