SUN-418 An Uncommon Case of Anti-PD1 Agent Induced Secondary Adrenal Insufficiency

Introduction - Nivolumab is a monoclonal anti-programmed cell death receptor 1(PD1) antibody approved for the treatment of unresectable or metastatic melanoma and is known to be associated with a wide spectrum of endocrinologic derangements. The objective of this report is to describe a case of symptomatic hyponatremia secondary to hypophysitis induced by nivolumab immunotherapy. Case Report - A 63-year-old male with Stage 4 malignant melanoma presented for the administration of cycle 6 maintenance therapy nivolumab. He was noted to be awake but disoriented to time and place, and family members reported worsening confusion for the previous three days. His labs revealed low serum sodium (120mEq/L; 135-145 mEq/L), and he was admitted for further management. His medical history includes immune-mediated hypothyroidism secondary to nivolumab and is on levothyroxine supplementation. His initial workup showed hypotonic, euvolemic hyponatremia. Given his known adrenal metastasis, primary adrenal insufficiency (PAI) was in the differential. A morning serum cortisol level was low (3.3μg/dL; 7-28 μg/dL), and a low dose ACTH stimulation test was abnormal concerning for PAI. Curiously, his ACTH level was inappropriately low (7 pg/mL; 20-52 pg/mL) for PAI, suggestive of secondary adrenal insufficiency. MRI-brain showed mild diffuse interval enlargement in size, as well as homogeneous contrast enhancement of pituitary gland. The patient was started on hydrocortisone treatment, and the hyponatremia resolved. Diagnosis of hyponatremia secondary to hypophysitis from nivolumab therapy was established. Screening for other pituitary hormone deficiency resulted in normal FSH, LH, TSH, prolactin, IGF-1 levels. Also, serum renin, aldosterone, free and total testosterone levels were unremarkable. With clinical improvement, the patient was discharged home on maintenance dose hydrocortisone.Discussion - This report highlights a rare case of nivolumab-induced secondary adrenal insufficiency where early recognition and management plays a crucial role. Nivolumab acts by restoring natural T-Cell mediated immune response and incites concomitant T cell activation against normal tissues. This leads to immune-related adverse events mainly affecting multiple endocrine glands in an insidious manner. At present, anti-PD1 agents are widely used in clinical practice. Hypotension, hyponatremia or persistent hypoglycemia in patients receiving these agents warrant screening for adrenal insufficiency in order to prevent deleterious clinical consequences.