SAT-055 - ACTH Elevation Prior to the Development of Immune Checkpoint Inhibitor-Associated Hypophysitis: A Case Series

Background
As immune checkpoint inhibitors (ICI) are increasingly used in cancer therapy, more patients are at risk for immune-related adverse events. Patients with ICI-associated hypophysitis typically present with secondary adrenal insufficiency characterized by low cortisol and low or inappropriately normal ACTH levels. Its mechanisms and pathophysiology remain unclear, but early identification is critical given the risk of life-threatening adrenal crisis. We describe 3 cases where a sudden increase in ACTH levels occurred immediately prior to the development of hypophysitis.

Clinical Cases:
1: A 42 yo woman with metastatic breast cancer was treated with neoadjuvant chemotherapy and pembrolizumab for 4 cycles prior to bilateral mastectomy, then continued pembrolizumab every 3 weeks. Her baseline ACTH and cortisol were 26.1 pg/mL (ref: 9-60pg/mL) and 10.4 µg/dL (ref: 5-25µg/dL). ACTH and cortisol were monitored and normal before each cycle. Prior to cycle 7, her ACTH rose to 75.7 pg/mL (cortisol: 9.7 µg/dL). Prior to cycle 8, she had nausea, fatigue, and dizziness, with labs significant for an ACTH and cortisol of 3.7 pg/mL and 0.4 µg/dL. Imaging showed a prominent pituitary gland, and she was started on hydrocortisone for hypophysitis.

2: A 76 yo man with metastatic mesothelioma was treated with Ipilimumab and Nivolumab. His baseline ACTH and cortisol were 12.5 pg/mL and 25.6 µg/dL. Prior to cycle 2, his ACTH rose to 93.9 pg/mL (cortisol: 14.6 µg/dL). Given worsening headache, nausea, and fatigue, he had repeat labs 1 week later, with an ACTH and cortisol of 50.4 pg/mL and 1.2 µg/dL. Pituitary MRI was notable for an enlarged and hyperenhancing pituitary gland and pituitary stalk consistent with hypophysitis. The patient was started on hydrocortisone, with improvement in symptoms.

3: A 50 yo man with melanoma was treated with encorafenib and binimetinib for 3 months, then transitioned to ipilimumab and nivolumab given disease progression. His baseline ACTH and cortisol were 20.5 pg/mL and 11.2 µg/dL. After cycle 1, the patient developed severe headaches. His MRI showed thickening of the pituitary and pituitary stalk, causing compression of the optic chiasm. His ACTH was 91 pg/mL (cortisol: 24.1 µg/dL). The patient was started on high dose steroids 1mg/kg given his symptoms and MRI. He was then tapered to physiologic hydrocortisone dosing, with resolution of the pituitary enlargement on repeat MRI.

Conclusion
In our 3 case patients treated with ICIs, transient elevations in ACTH after ICI exposure preceded the onset of hypophysitis. A sudden increase in ACTH may reflect inflammation or destruction of the pituitary gland, and patients should be carefully monitored for the development of secondary adrenal insufficiency. Further research is needed to understand the mechanisms of immunotherapy-associated hypophysitis, and determine if fluctuations in ACTH can predict the onset of hypophysitis.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*