Side Effect: Inflammation of the pituitary gland (hypophysitis)

What is Inflammation of the pituitary gland (hypophysitis)?

Inflammation of the pituitary gland, also known as hypophysitis, is a disorder that affects the pituitary, which is a small gland located at the base of the brain that produces hormones that regulate several bodily functions.

What does Inflammation of the pituitary gland (hypophysitis) look like?

Hypophysitis can present with different clinical features depending upon the underlying cause and the extent of pituitary gland damage. Some common signs and symptoms of hypophysitis include:

• Headache
• Fatigue
• Dizziness
• Nausea/vomiting
• Decreased appetite
• Visual disturbances
• Confusion

Who gets Inflammation of the pituitary gland (hypophysitis)?

Hypophysitis can occur as an immune-related adverse event (irAE) in patients with cancer who are receiving immune checkpoint inhibitor (ICI) therapy such as:

PD-1 inhibitors:

• pembrolizumab (Keytruda®)
• nivolumab (Opdivo®)
• cemiplimab (Libtayo®)
• dostarlimab (Jemperli®)
• retifanlimab (Zynyz®)
• toripalimab (Loqtorzi®)

PD-L1 inhibitors:

• atezolizumab (Tecentriq®)
• durvalumab (Imfinzi®)
• avelumab (Bavencio®)

CTLA-4 inhibitors:

• ipilimumab (Yervoy®)
• tremelimumab (Imjudo®)

ICIs activate the immune system against cancer cells, but they can also trigger an immune response against healthy tissues, including the pituitary gland, leading to hypophysitis. Hypophysitis is a rare but potentially serious irAE that can occur with ICIs. Other cancer treatments, such as radiation therapy and chemotherapy, have also been reported to cause hypophysitis in rare cases.

How to prevent Inflammation of the pituitary gland (hypophysitis)

• Prevention of hypophysitis in patients with cancer is challenging, as the condition is primarily an immune-mediated adverse event of cancer treatment, and is not always predictable.
• Close monitoring of patients receiving ICIs is essential to detect and manage hypophysitis early.
• Patients should be educated about the signs and symptoms of hypophysitis (listed above) and promptly seek medical attention if they experience any of these symptoms after receiving treatment.

How to treat Inflammation of the pituitary gland (hypophysitis)

The initial management of hypophysitis typically involves stopping or temporarily suspending the ICI therapy and initiating hormone replacement therapy to address any hormonal deficiencies. Hormone replacement therapy may include the following medications:

• Hydrocortisone (Cortef®, Solu-Cortef®)
• Levothyroxine (Synthroid®)
• Testosterone
• Estrogen

In more severe cases, other glucocorticoids such as prednisone (Deltasone®) or methylprednisolone (Solu-Medrol®), may be necessary to reduce inflammation and prevent further damage to the pituitary gland.