Nivolumab Induced Adrenal Insufficiency: Rare Side-effect of a New Anti-cancer Therapy - Immune-checkpoint Inhibitors.

Abstract

Immune-checkpoint inhibitors are immuno-modulatory antibodies used in patients with advanced cancers like melanoma, renal cell carcinoma, non-small cell lung cancer, etc. They are associated with a wide array of side effects, commonly known as immune-related adverse events (irAEs), affecting dermatological, gastrointestinal, hepatic, endocrine, and other systems. We present a case of nivolumab-induced adrenal insufficiency in a patient presenting with refractory hypotension. The patient is a 77-year-old caucasian male with metastatic renal cell carcinoma (RCC) on nivolumab therapy, presented to his primary doctor for symptoms of fatigue, weakness, loss of appetite, and dizziness. His initial blood pressure (BP) was noted to be 78/44 mmHg, so he was referred to the emergency department. He received several liters of intravenous (IV) fluid boluses; however, BP consistently stayed in 90s systolic and 40-50 diastolic. The lab investigations showed a low sodium level at 128 mmol/L, blood urea nitrogen (BUN) elevated at 37 mg/dL, creatinine elevated at 2.7 mg/dL. A morning cortisol level was checked; it came back low at 1.3 mcg/dL. Further testing with the cosyntropin stimulation test revealed low basal cortisol of 1 mcg/dL and only a mild increase to 10.20 mcg/dL after the cosyntropin administration. Adrenocorticotrophic hormone (ACTH) was checked that came out to be low <5pg/mL, favoring a diagnosis of secondary adrenal insufficiency likely due to hypophysitis. In the meantime, the patient was started on hydrocortisone, which improved his blood pressure significantly. He was eventually weaned from IV hydrocortisone to p.o. hydrocortisone. The nivolumab was discontinued, and oncology decided on giving a nivolumab re-challenge once the patient was stabilized. Our patient presented with common manifestations of adrenal insufficiency like fatigue, hypotension, and hyponatremia, which is one of the rare irAEs occurring in <1% of the patients. These are non-specific manifestations and can be easily overlooked if adverse events of immunotherapy are not suspected. Even though rare, adrenal insufficiency is a life-threatening side-effect of immune checkpoint inhibitor drugs that need to be recognized immediately and managed with intravenous glucocorticoids.