Treatment options for immunotherapy associated hypophysitis

What is the treatment options for and natural history of IH?

Physiologic or supraphysiologic glucocorticoid therapy has been frequently used to treat IH, although evidence is lacking that this changes the natural history of the inflammatory process, or improves long-term pituitary function. In general, a brief course of higher dose steroids is recommended for hypophysitis associated with severe headaches, significant hyponatremia, adrenal crisis or pituitary enlargement associated with optic nerve compression (or for other IRAEs which may require high-dose steroids, such as colitis, hepatitis, pneumonitis, etc.). Otherwise, physiologic glucocorticoid therapy (e.g., prednisone 5 mg/day or hydrocortisone 15–20 mg/day) is recommended for central adrenal insufficiency, which is commonly associated with ipilimumab-induced hypophysitis. Importantly the use of high-dose glucocorticoids, but not physiologic glucocorticoids, adversely affects the anticancer response to therapy. Lastly, in addition to possible glucocorticoid replacement, other pituitary deficiencies should be replaced as appropriate.

Resolution of radiographic pituitary/stalk enlargement occurs in the vast majority of cases and usually within several weeks to months of onset. In addition, a reduced pituitary volume or empty sella are commonly observed. With regard to hypopituitarism, a portion of patients with IH may recover some anterior pituitary function, although persistent central adrenal insufficiency, central hypothyroidism, and central hypogonadism are common in an estimated 85%, 40%, and 40% of cases, respectively.


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