How Novel Cancer Therapies Affect Your Endocrine System

By: 
Mahmoud Alsayed, MD and Ricardo Correa, MD, Es. D, FACP, CMQ

General concepts

Cancer cells can develop tolerance to the immune system by suppressing immune cells called T cells, which are known to be critical for our body’s immune response. The action of this tolerance is through immune checkpoints. Checkpoint inhibitors are a form of cancer immunotherapy, targeting these immune checkpoints. These types of medications have substantially improved the prognosis for patients with certain types of cancer, including melanoma, lung, bladder, and kidney cancer, among others.

In medicine, all of our pharmacotherapies come with a cost. Even though these medications have been proven to improve survival, there is a significant risk for immune-related adverse events, and are commonly presented in the skin, gastrointestinal and endocrine systems (Figure 1).

It is essential to understand that the immune-related adverse events can occur at any time from the beginning of treatment, during treatment, or after treatment has been discontinued. These events can resolve completely after appropriate therapy is administered, but in some cases where the endocrine system is affected, permanent hormone replacement therapy may be required. Furthermore, the use of more than one checkpoint inhibitor at the same time increases the risk of side effects presenting faster and being more severe.

Endocrinopathies

Immune-related adverse events can affect any endocrine organ. The most common endocrine adverse events involve thyroid dysfunction, including hypothyroidism, hyperthyroidism, and thyroiditis. Thyroid dysfunction is reported in 6-20% of patients taking these medications. Thyroiditis, which results from destruction of thyroid cells, is the most prevalent. Patients typically need thyroid hormone replacement lifelong.

It is essential to understand that the immune-related adverse events can occur at any time from the beginning of treatment, during treatment, or after treatment has been discontinued.

The pituitary, the adrenal glands and the pancreas are other endocrine organs that can be affected. Hypophysitis is any inflammation in the pituitary gland and recently checkpoint inhibitors were added to the list of medications that can cause it. Pituitary dysfunction may affect multiple organs and hormone levels, like thyroid hormone, cortisol, testosterone or estrogen. Presentation can be subtle and difficult to differentiate from the primary malignancy or its treatment. Correct diagnosis requires critical thinking and a comprehensive workup. For instance, checking pituitary hormone levels without testing the blood levels of target hormones can give false reassurance. Adrenal glands produce important hormones, but cortisol is the most important one to thrive especially if patients are acutely ill or fighting cancer. Adrenalitis, which is inflammation of the adrenal glands, can result from immune checkpoint inhibitor use and can lead to low levels of cortisol. Appropriate diagnosis and treatment for adrenal insufficiency is extremely important. Diabetes mellitus can also result from immune-mediated destruction of pancreatic beta-cells, which are the cells synthesizing and producing insulin. In patients taking immune checkpoint inhibitors, new onset of hyperglycemia should prompt evaluation for new onset diabetes and expedite insulin use if appropriate.

In conclusion, even though immune checkpoint inhibitors have provided cancer patients with a promising new approach for treatment of advanced cancer, physicians and patients should be aware of the possibility of developing immune-related adverse events that can affect many organs. Endocrinopathies are immune-related adverse events that may result from use of these novel medications and can be managed with hormone replacement therapy depending on the affected organ by a specialist. These adverse events should not discourage the use of these medications as they have been shown to improve survival in a significant portion of patients with certain cancers.

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