SUN-447 - When Immunotherapy Backfires: A Case of Autoimmune Adrenalitis Following PD-1 Inhibitor Therapy

Introduction:
Immune checkpoint inhibitors (ICI) offer significant clinical benefits in the treatment of malignancies. However, their use is associated with several adverse effects, mostly commonly endocrinopathies, which include adrenal insufficiency (AI).

Case Description:
An 85-year-old female with history of lung cancer on immunotherapy with cemiplimab, initiated 5 months prior to presentation, was admitted for generalized weakness. On presentation, vital signs were within normal limits. Initial labs were remarkable for sodium of 120 mmol/L (135-145 mmol/L), potassium of 5.3 mmol/L (3.4-5.3 mmol/L), and morning cortisol of < 0.5 mcg/dL (5.2- 22.5 mcg/dL). Two days after admission, blood pressure was noted to be 76/45 mmHg requiring initiation of vasopressors and empiric antibiotics followed by transfer to the intensive care unit. Infectious work-up with computed tomography (CT) abdomen and pelvis did not show any infectious sources. Blood cultures showed no growth, and urine cultures were positive for Escherichia coli. Repeat testing with total cortisol was < 0.5 mcg/dL (3.4 -22.5 mcg/dL). Imaging revealed normal adrenal glands on CT abdomen and pelvis and normal pituitary on CT head. Treatment was initiated with one dose of IV hydrocortisone 100 mg followed by 50 mg every 6 hours with improvement of clinical signs and symptoms. Systolic blood pressures improved to 120-140 mmHg, sodium level to 129 mmol/L, and potassium to 4.2 mmol/L. Further work-up revealed a positive 21-hydroxylase antibody, supporting the diagnosis of primary AI. She was discharged on hydrocortisone 20 mg in the morning and 10 mg in the evening along with fludrocortisone 0.05 mg a day.

Discussion/

Conclusion:
Adrenal insufficiency secondary to ICI therapy can occur at any time during therapy and may present as a life-threatening emergency. Primary AI from ICI use is classified as extremely rare, occurring in approximately 0.7% of patients. Clinical manifestations are often nonspecific, including fatigue and weight loss but can progress to severe hypotension and electrolyte disturbances, typically hyponatremia and hyperkalemia. There is currently no standardized screening algorithm for early detection of ICI-related adrenal insufficiency; however, serial electrolyte and fasting cortisol measurements can help detect signs of AI to help initiate early treatment with lifetime glucocorticoid supplementation.

References:
Salinas C, Renner A, Rojas C, Samtani S, Burotto M. Primary Adrenal Insufficiency during Immune Checkpoint Inhibitor Treatment: Case Reports and Review of the Literature. Case Rep Oncol. 2020;13(2):621-626. Published 2020 Jun 9. doi:10.1159/000507652
Grouthier V, Lebrun-Vignes B, Moey M, et al. Immune Checkpoint Inhibitor-Associated Primary Adrenal Insufficiency: WHO VigiBase Report Analysis. Oncologist. 2020;25(8):696-701. doi:10.1634/theoncologist.2019-0555

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