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Why Isn’t Block and Replace Therapy Commonly Recommended?

In past articles and blog posts I have discussed some of the different conventional medical treatment options for hyperthyroid conditions, but I haven’t discussed something called block and replace therapy.  One of the main reasons for this is because this is rarely recommended to those with hyperthyroidism and Graves’ Disease, although every now and then I’ll work with someone who was recommended to receive this treatment by their endocrinologist.  As a result, I figured it was time to put together a brief post on this topic.

So what exactly is block and replace therapy?  Well, many people with hyperthyroid conditions are told to take antithyroid medication, which includes Methimazole, Carbimazole, and PTU.  These are given to “block” the production of thyroid hormone [1], and antithyroid medication accomplishes this by inhibiting an enzyme called thyroid peroxidase.  What it specifically does is inhibit the metabolism of iodide and the iodination of tyrosine residues in the thyroid hormone precursor thyroglobulin by thyroid peroxidase (1) [2].

One problem with antithyroid medication [3] is that people who take it commonly become hypothyroid.  So for example, it’s common for someone with elevated thyroid hormone levels to get a prescription for antithyroid medication, and when doing a follow-up thyroid panel their thyroid hormone levels will be low, while their TSH will be on the high side.  When this is the case, the medical doctor will usually lower the dosage of antithyroid medication and hope that the next thyroid panel will show a lower TSH and higher thyroid hormone levels, but at the same time prevent the person from becoming hyperthyroid again.

The “Seesaw” Effect of Antithyroid Medication

Sometimes this can become a frustrating process for the patient, as I’ve worked with people who were told to take a higher dosage of antithyroid medication, and then when the thyroid panel revealed a hypothyroid state the dosage was greatly reduced, and in some cases the patient was told to stop taking the Methimazole, and the person became hyperthyroid again.  So for example, a person with Graves’ Disease or toxic multinodular goiter might be told to take 40mg of Methimazole, and the next thyroid panel presents with hypothyroid numbers (elevated TSH and low thyroid hormone levels), and so the person’s dosage is reduced to 10mg, only to have the person become hyperthyroid again.

With block and replace therapy, the person isn’t only put on antithyroid medication to “block” the production of thyroid hormone, but they are also given thyroid hormone replacement (i.e. levothyroxine).  So it’s almost like a balancing act, as the antithyroid medication will prevent the person from becoming hyperthyroid, but the person is also given some thyroid hormone to prevent them from becoming hypothyroid.  Block and replace therapy is usually reserved for moderate to severe cases of hyperthyroidism, as with this treatment higher doses of antithyroid medication are usually taken by the patient.

Why Is Block and Replace Therapy Seldom Used?

Rarely does an endocrinologist [4] in the United States recommend block and replace therapy, and it also isn’t commonly recommended by medical doctors in other countries.  One reason for this is because the relapse rates are comparable to someone who is taking antithyroid medication alone, but another reason is because side effects seem to be more common with block and replace therapy (2) [5].  Another thing to keep in mind is that most endocrinologists are far more concerned about managing hyperthyroidism, which is why many will recommend radioactive iodine or thyroid surgery as the first line of treatment.  In other words, many aren’t concerned if their hyperthyroid patients become hypothyroid by taking antithyroid medication.

This doesn’t mean that there aren’t times when block and replace therapy can be beneficial.  For example, pregnant women with hyperthyroidism are usually told to take antithyroid medication.  While many people are understandably concerned about the effects of these medications on the liver, another concern during pregnancy is that antithyroid medication can lead to hypothyroidism.  And of course thyroid hormone is very important for the developing fetus.  Block and replace therapy during pregnancy was discussed in a case study involving a 36-year old woman, as the authors explained how it is challenging to keep the free T4 in the upper range of normal with antithyroid medication alone, and that block and replace therapy can prevent fetal hypothyroidism from developing (3) [6].

Graves’ orbitopathy might be another situation where block and replace therapy is indicated, as a study showed that using long-term block and replacement therapy until Graves’ orbitopathy becomes inactive might be a good option (4) [7].  One thing to keep in mind was that the patients in this study were treated with block and replace therapy for an average of 41 months, and many endocrinologists would refuse to have their patients take antithyroid medication for that long, even if the liver enzymes [8] were fine during treatment.

The truth is that block and replace therapy might be beneficial in certain situations, but most endocrinologists are trained to prescribe antithyroid medication alone, which is why they commonly recommend this to their patients with hyperthyroidism and Graves’ Disease.  In fact, some endocrinologists aren’t even familiar with block and replace therapy, and one reason for this is because only a small percentage of their patients have hyperthyroidism and Graves’ Disease.  It is far more common for endocrinologists to deal with patients who have Hashimoto’s thyroiditis.  As a result, those with a hyperthyroid condition can expect to be advised to take antithyroid medication by their endocrinologist, or to receive radioactive iodine or thyroid surgery.

In summary, block and replace therapy involves taking both antithyroid medication and thyroid hormone.  So essentially the goal is to block the production of thyroid hormone, but at the same time have the patient take thyroid hormone replacement to prevent them from becoming hypothyroid.  Block and replace therapy is rarely recommended by endocrinologists, and two reasons for this are because 1) the relapse rate is comparable to taking antithyroid medication alone, and 2) side effects are more common.  However, pregnancy and Graves’ orbitopathy are two situations when this type of treatment might offer some benefits.