Case Presentation: A 70 year old male with a history of urothelial cancer on nivolumab presented to the hospital for confusion. Patient developed worsening confusion over the past two days causing family to take him to the emergency room. He was initially hemodynamically stable though he was found to have a sodium of 116. He was thus admitted to the hospital medicine service for further workup. His urine sodium was 53 mmol/L and urine osmolality 209 mOsm/kg and he was thought potentially to have SIADH though he had no new concerning medications nor identified pulmonary or neurologic signs, symptoms or pathology. On hospital day 2, he developed hypotension to 79/44 (afebrile HR 81) that was refractory to fluid bolus administration causing transfer to ICU and initiation of norepinephrine. He was started empirically on broad spectrum antibiotics though infectious workup including chest x-ray, urinalysis, procalcitonin, and respiratory viral panel were negative. AM cortisol level obtained at 3 AM was < 1.0 mcg/dL and TSH/T4 was found to be .51 ng/dL and 7.34 mIU/L respectively. Patient was placed on stress dose steroids with subsequent resolution of vasopressor requirements and transferred back to the internal medicine service. Blood cultures remained negative at 48 hours and patient was stable off antibiotics. ACTH stimulation test was deferred given recent steroid administration. Patient ultimately thought to have developed adrenal insufficiency and hypothyroidism secondary to nivolumab therapy. Nivolumab was discontinued by outpatient oncology.
Discussion: Given the proliferation of immune check point inhibitors (ICI) since their FDA approval in 2011 for the treatment of cancer, the incidence of ICI toxicity has increased significantly in recent years. Endocrinopathy related ICI toxicity is common affecting up to 40% of patients. In descending order, thyroid, pituitary and then adrenal glands are the most commonly affected endocrine organs. Pituitary gland involvement can present as secondary adrenal insufficiency including adrenal crisis.This patient’s urine studies were originally attributed to SIADH even though there was no overt cause of SIADH. Critically, adrenal insufficiency as a rare cause of hyponatremia and has a similar urine chemistry profile as SIADH (urine sodium over 40 mmol/L and urine osmolality over 100 mOsm/kg). In this case, the urine studies were the first signs of this patient’s adrenal insufficiency. Distinguishing between Nivolumab induced primary versus secondary adrenal insufficiency was not possible in this case as patient had already received treatment dosed steroids prior to ACTH measurement.
Conclusions: Prompt recognition and treatment of endocrinologic emergencies in ICI toxicity, such as adrenal crisis secondary to Nivolumab, can be critical in preventing patient deterioration events such as rapid responses, ICU escalation and mortality.