Tackling Amiodarone-Induced Hyperthyroidism: A Delicate Balance

Boris Hansel, MD; Igor Tauveron, MD, PhD

Disclosures

March 23, 2018

Editor's Note: The following is an edited, translated transcript of a conversation between Boris Hansel, MD, endocrinologist-nutritionist, and Igor Tauveron, MD, PhD, professor of endocrinology in Clermont-Ferrand, France. It was taped on January 17, 2018, during the European Days of the French Society of Cardiology Conference.

Hansel: Hello, and welcome to Medscape. This webcast is devoted to the relationship between the heart and the thyroid gland, specifically amiodarone-induced hyperthyroidism. I am joined by Professor Igor Tauveron, chief of endocrinology at the University Hospital Center of Clermont-Ferrand, France. Igor, you presented a paper at the January 2018 European Days of the French Society of Cardiology Conference, where an entire session was devoted to the relationship between the heart and the thyroid.

It is quite common for a cardiologist to call an endocrinologist with the following problem: "I have a patient who is taking amiodarone, and he is now hyperthyroid. What should I do?" It is also quite common for an endocrinologist to be in a bind because he knows that he has a patient with amiodarone-induced hyperthyroidism and doesn't dare discontinue the amiodarone because of the cardiac risk. We need practical, concrete solutions for this dilemma.

When I initiate amiodarone, when should I check the thyroid-stimulating hormone (TSH) level?

Tauveron: I believe one should start straightaway. We must bear in mind that about 15% of patients who receive amiodarone develop a thyroid sequela, be it hypo- or hyperthyroidism. Therefore, when initiating amiodarone, and ideally before but at most within a few hours after, one should measure the thyroid hormones—the TSH and the peripheral hormones, thyroxine (T4) and triiodothyronine (T3), because amiodarone impregnation has a biological effect that changes these parameters.

Hansel: Let's start by excluding two straightforward phenomena that occur with amiodarone. The first is physiologic changes in the thyroid function tests in the first few days after initiating amiodarone. They are expected and should not cause any alarm.

Tauveron: Right. Amiodarone blocks the conversion of T4 to T3 in all patients. Consequently, their T4 levels will increase and T3 levels will decrease. After a few fluctuations, the TSH values will return to baseline in a few weeks. First message: The T4 increases in all patients, and the T3 decreases in all patients.

Hansel: We can tolerate the T4 increasing to slightly above normal and the T3 decreasing to slightly below normal.

Tauveron: Definitely. We can safely exceed the normal range by 25%.

Hansel: Are we talking about the first month after initiating amiodarone?

Tauveron: We are talking about the entire time the patient is on amiodarone. This happens after a few weeks and persists for as long as the patient is taking it.

Hansel: A second phenomenon is amiodarone-induced hypothyroidism, in which the T4 and even the T3 levels drop considerably, and the TSH level increases. Is that also a straightforward event?

Tauveron: It's extremely straightforward. The patient should continue taking amiodarone, if clearly necessary, and thyroid hormone replacement should be added, if needed, with prudent goals, because the patient has an underlying heart condition and should not be overdosed with thyroid hormones. That would cause, at the least, iatrogenic hyperthyroidism and exacerbate the underlying thyroid disorder. Thus, one should bring the TSH down to within the normal range or slightly above it.

Hansel: Perhaps consult an endocrinologist, or perhaps the cardiologist can do this if he or she has some experience, by introducing thyroid hormones and checking the patient's thyroid function two or three times a year in order to adjust the thyroid hormone therapy.

Tauveron: Definitely. The hypothyroidism strategy is straightforward.

Hansel: Let's talk now about the more complicated case: a patient with persistent hyperthyroidism. His TSH secretion is slowed, and his free hormones have increased with amiodarone. What should one do? First, we should diagnose the type of hyperthyroidism, correct?

Tauveron: Definitely. This is important. For this purpose, I encourage cardiologists to perform cervical ultrasound as soon as the patient is put on amiodarone, because there are two types of amiodarone-induced hyperthyroidism. Type 1 hyperthyroidism occurs in a diseased thyroid with increased vascular flow; type 2 occurs in a healthy thyroid with severely diminished vascular flow. The therapeutic strategy will be completely different, depending on the type.

Hansel: In the first type, you have a diseased thyroid, possibly with thyroid nodules, whereas in the second type, you have a healthy thyroid, and amiodarone-related inflammation is causing the hyperthyroidism. This is why ultrasound should be done as soon as the patient is put on amiodarone.

Tauveron: And ultrasound should be done again if the patient is hyperthyroid, to assess the vascular flow at that point. You can also order a scan, but a scan's relevance is more debatable.

Hansel: But in the case of ultrasound, should one always order Doppler?

Tauveron: Naturally, it would be Doppler ultrasound, which is performed by all contemporary radiologists.

Hansel: Thank you. Let's examine the first situation: hyperthyroidism in a patient with thyroid abnormalities.

Hyperthyroidism in a Patient With Thyroid Abnormalities

Tauveron: The objective will be to flush iodine from the thyroid and reduce thyroid hormone synthesis. We will therefore prescribe high-dose synthetic antithyroids and, if the response is inadequate after about 3 weeks, add a drug called perchlorate, which flushes iodine from thyroid cells.

Hansel: Should the amiodarone be discontinued? What's the scoop on that?

Tauveron: Should amiodarone be discontinued? I don't know. When you look at the surveys of endocrinologists in the learned societies, only 30% dare to continue amiodarone. Yet, when you look at the recommendations and the literature, there is no formal consensus. I really believe the decision should be made on a case-by-case basis, because it depends on the patient's clinical status, the severity of the hyperthyroidism, and the underlying cardiac status. Keep this in mind: When you stop amiodarone, the effect continues for at least 140 days.

Hansel: In other words, don't expect an immediate or near-immediate remission from the hyperthyroidism.

Tauveron: Exactly.

Hansel: At the end of the day, the cardiac risk persists for several weeks or several months.

Tauveron: Absolutely. And amiodarone has an antithyroid effect on the heart that is opposite that of thyroid hormones, which is a cardioprotective effect. In other words, what is gained on the one hand is perhaps lost from the other.

Hansel: Thus, in some cases, you should recommend discontinuing amiodarone, whereas in others, you should recommend continuing it. And you said that only 30% of endocrinologists would agree to have the patient continue taking it, which means that we endocrinologists are not trained to have patients continue amiodarone. Consequently, for these problems, one should perhaps turn to an ultraspecialist.

Tauveron: Exactly. I definitely think that that makes sense.

Amiodarone-Induced Hyperthyroidism in a Healthy Thyroid

Hansel: The second scenario is amiodarone-induced hyperthyroidism in a healthy thyroid, with an ultrasound showing a normal thyroid.

Tauveron: The patient has thyroid inflammation, which can't be seen on the ultrasound. The patient has very low vascular flow; a normal thyroid on ultrasound; and, in theory, a white scan. We should note that we can give this a bit of time before jumping in, because more than one half of these cases regress spontaneously.

Hansel: While the patient is taking amiodarone?

Tauveron: Ah! That is the debate, but one half regress spontaneously, and if this doesn't happen after a few weeks, you should not wait much longer. You should initiate glucocorticoids to obtain both a peripheral antithyroid effect and an anti-inflammatory effect in the thyroid gland.

Hansel: In this case, the same question and perhaps the same answer: Should amiodarone be systematically discontinued?

Tauveron: Amiodarone should not be systematically discontinued. There is even less reason to discontinue it in this situation.

Reintroducing Amiodarone?

Hansel: Let's assume that the amiodarone-induced hyperthyroidism has resolved, perhaps because we treated it, and we discontinued the amiodarone. We are faced with the following question because we have been told that there is a major and even consistent risk for recurrence: Can we reintroduce amiodarone? You have some statistics for us today, because your group reported a series of patients with amiodarone-induced thyrotoxicosis who subsequently received amiodarone again.

Tauveron: One of my assistants had the brilliant idea of determining what would happen when we reintroduced amiodarone. Dr Salwan Maqdasy published our results in the American Journal of Cardiology 2 years ago.[1] We found two things. First when we introduced amiodarone in patients with type 2 hyperthyroidism and a healthy thyroid, only 20% experienced a recurrence. This means that 80% did not, which is no small matter. By contrast, more than two thirds of the patients with type 1 hyperthyroidism experienced a recurrence.

Therefore, what we recommend in type 2 hyperthyroidism is to reintroduce amiodarone and closely monitor the patient's thyroid hormones. In my opinion, levels should be checked every 6-8 weeks. In type 1 hyperthyroidism—that is, in a diseased thyroid—we recommend proceeding with caution. And perhaps one of these hypotheses, which no one had ventured to put forth before we did, is to systematically reintroduce amiodarone in addition to or together with low-dose synthetic antithyroids to prevent a runaway thyroid.

Our study is limited in that we had only 40 patients, but given the absence of evidence for most of the data on amiodarone-induced hyperthyroidism, I think we can defend this strategy.

When to Perform Thyroidectomy

Hansel: One last strategy is to perform thyroidectomy. We're not going to talk about life-saving thyroidectomy in severe, treatment-resistant hyperthyroidism, where you have situations that sometimes involve resuscitation with thyroidectomy or apheresis/plasmapheresis. We are not going to broach this very specific topic.

Let's talk instead about amiodarone-induced hyperthyroidism that is in remission. In this case, another strategy would be to perform thyroidectomy in order to be able to reintroduce amiodarone.

Tauveron: That's correct. This is the current trend. When the patient has returned to a euthyroid state and the situation is being controlled, we may as well propose a radical treatment. In this case, we have two strategies: thyroid surgery (that is, thyroidectomy) or radioactive iodine. Each has its benefits and drawbacks.

Radioactive iodine takes a long time to act. You sometimes have to wait a year, and therefore you aren't sure about the outcome for a long time. Thyroidectomy confers an immediate benefit, but it is not without risk. It should be noted that in the only series in the literature, conducted by the Mayo Clinic, 9% of patients died after this procedure, whereas the figure is substantially less than 1% in the general population.[2] These patients are extremely fragile from a cardiovascular standpoint, and the prognosis depends more on their underlying cardiovascular status.

Hansel: So, the key takeaways are as follows:

  • Carefully distinguish between type 1 and type 2 hyperthyroidism, because the risk for recurrence and the treatments to be used are fundamentally different.

  • Amiodarone-induced hypothyroidism does not pose a problem. Don't discontinue amiodarone in the event of hypothyroidism. However, hyperthyroidism should be treated.

  • Amiodarone can even be initiated in a patient at risk for hyperthyroidism, but under a watchful eye in certain cases, and more successfully in patients with type 2 than type 1 hyperthyroidism.

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