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Thyroid Disorders
How I Manage Thyroid Disorders in Cancer Survivors

Released: April 26, 2021

Expiration: April 25, 2022

Steven G. Waguespack
Steven G. Waguespack, MD
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In this commentary, I answer questions from a symposium on late endocrine effects in cancer survivors. Slides from the symposium are also available for self-study or to use in your noncommercial presentations. 

In patients who develop hypothyroidism due to immune checkpoint inhibitors, are there data to guide thyroid replacement? Should long-term thyroid function recovery be expected?

In this context, I am not aware of data that guide thyroid hormone replacement, which should be similar to other cases of primary hypothyroidism.

One thing to remember is that, as thyroid dysfunction evolves from acute hyperthyroidism to hypothyroidism, there is a period when the free thyroxine (T4) will be low with a nonelevated thyroid-stimulating hormone (TSH). Therefore, I initiate full-dose levothyroxine once the free T4 is clearly low, even in the absence of an elevated TSH.

Thyroid recovery does occur in some patients and probably relates to the extent of thyroid destruction and the degree of thyrotoxicosis. The majority of patients, however, will need long-term levothyroxine replacement.

Is it reasonable to treat mild, compensated hypothyroidism following metaiodobenzylguanidine (MIBG) treatment?

Yes, if the TSH is confirmed to be elevated, I would start levothyroxine to keep the TSH in the low-normal range with hopes of mitigating the risk of developing subsequent thyroid neoplasia. This is also how I approach hypothyroidism after external radiation therapy when the thyroid gland is in the radiation field.

Does hypothyroidism caused by mitotane persist? Are there guidelines on how it should be monitored?

This is an area that remains poorly studied. The use of mitotane for adrenocortical carcinoma can result in central hypothyroidism, which I would expect to occur 3-6 months after mitotane is started and especially once mitotane levels become therapeutic.

There are no clear guidelines of which I am aware, but I would consider monitoring thyroid function studies every 3 months at the outset.

Data on long-term outcomes are scarce, but this has been reported as reversible. It would be worthwhile to re-evaluate the hypothalamic–pituitary–thyroid axis in long-term survivors.  

What is the mechanism of hyperthyroidism as a late effect?

I’ve always struggled with the concept of primary hyperthyroidism as a late effect after cancer treatment, which I have found to be extraordinarily rare in my practice (similar to the experience of other panelists and experts in this field).

The difficulty with understanding the true risk is that most studies in childhood cancer survivors are based on self‑reported data—data that cannot be confirmed to indicate true hyperthyroidism. For example, there is no way to go back and check thyroid autoantibodies or define what is meant by the term “hyperthyroidism,” which could also indicate overreplacement with levothyroxine in survivors with preexisting primary hypothyroidism or a misinterpreted low TSH in a patient with central hypothyroidism.  

Regarding the mechanism of action, there are 2 possibilities.

First is acute hyperthyroidism due to the direct effects of radiation (radiation thyroiditis), which would have a similar clinical course as that seen with immune checkpoint inhibitors and antiangiogenic tyrosine kinase inhibitors.  

The second possibility is hyperthyroidism akin to Graves disease, which has also been described after hematopoietic stem cell transplant and the adoptive transfer of TSH receptor–autoreactive lymphocytes from a donor with Graves disease.

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