MON-370 Isolated Secondary Adrenal Insufficiency in the Absence of Hypophysitis Secondary to Immune Checkpoint Inhibitors

BACKGROUND: Use of immune checkpoint inhibitors (ICPIs) for treating advanced malignancies has uncovered various endocrinopathies, often as immune-related adverse events (irAEs). CASE: A 72-year-old man with metastatic melanoma presented with a 1-week history of fatigue, dizziness, nausea and vomiting. He received ipilimumab, a CTLA-4 inhibitor, with nivolumab, a PD-1 inhibitor, for two months, then nivolumab alone for the past four months. On presentation, blood pressure was 94/67 mmHg; serum sodium was 124 mEq/L (reference range 136-142 mEq/L). Given a high suspicion for secondary adrenal insufficiency, random afternoon serum cortisol and ACTH levels were drawn immediately, and he was managed empirically with dexamethasone. Serum cortisol returned at 1.1 µg/dL (reference range: 2-14 µg/dL) with undetectable ACTH level, consistent with the diagnosis. No other pituitary hormonal insufficiencies were present. Magnetic resonance imaging revealed stable brain metastases, no hypophysitis and normal-sized pituitary fossa. He was discharged on prednisone 7.5 mg daily and subsequently transitioned to hydrocortisone 20 mg daily. During 18 months of follow-up, no recovery of the pituitary-adrenal axis and no further pituitary hormonal insufficiencies have occurred. DISCUSSION: Nivolumab and ipilimumab are ICPIs, augmenting T-cell function against tumor cells, and potentially against non-cancerous cells, the latter leading to irAEs, including various endocrinopathies. To date, there are 20 case reports of isolated secondary adrenal insufficiency without radiographic evidence of hypophysitis, as in our case. Median onset occurred at 5.1 months after initial ICPI exposure, with 15% of cases associated with a CTLA-4 inhibitor, 80% of cases associated with a PD-1 inhibitor, and 1 case of combination therapy. Prognosis for recovery is poor for adrenal insufficiency, ranging 0 to 19%, unlike other endocrinopathies such as secondary hypothyroidism or hypogonadism. Our case demonstrates that although symptoms of nausea, vomiting, and fatigue are common among oncology patients, clinical suspicion for adrenal insufficiency should remain high among patients receiving ICPIs.