Case Presentation: A 41-year-old male with a history of metastatic squamous cell lung cancer presented with anorexia and fatigue to the emergency department. The patient was diagnosed with metastatic squamous cell lung carcinoma one year prior and was started on Paclitaxel/Carboplatin and Nivolumab/Ipilimumab treatments. Prior to the current presentation, the patient had been experiencing palpitations for one month. He was discovered to have heart rates in the 150s bpm. Outpatient EKG revealed sinus tachycardia, and a CT chest / abdomen revealed lung mass, pulmonary nodules, and an expanding left adrenal mass. Several days later, he presented with nausea, stomach discomfort, and anorexia to the emergency department. He was noted to be tachycardic at 140 bpm and hypotensive with a BP of 80/40 mm Hg. Workup revealed a TSH of 0.01 mlU/L, free T4 of 2.23 ng/dl, and total T3 of 236 ng/dl. Infection was ruled out. A diagnosis of immunotherapy-induced hyperthyroidism was made, and he was discharged with methimazole and IV fluids after treatment. The patient experienced increased lethargy, nausea, and vomiting and he returned to ED in two days. Physical examination revealed lethargy, a blood pressure of 80/40 mm Hg, and a heart rate of 148 beats per minute. IV fluids were begun. A brain MRI revealed no evidence of acute disease. Cortisol levels at 8 a.m. were 0.3 ug/dL, and cosyntropin tests revealed minimal responses of 2.1 ug/dL at 30 minutes and 3.1 ug/dL at 60 minutes, indicating primary adrenal insufficiency. Concurrently drawn ACTH levels were less than 5 pg/mL, indicating secondary adrenal insufficiency. The patient was administered 100 mg of intravenous hydrocortisone every 8 hours coupled with IV fluids, resulting in significant clinical improvement. The patient was later discharged home on steroids.

Discussion: Immune checkpoint inhibitors, which are often used to treat cancer, are associated with substantial endocrine toxicities, such as thyroiditis, hypophysitis, and adrenalitis. These drugs are relatively new to clinical practice, and therefore no long-term trials exist that highlight their unknown effects on various organ systems. Cancer patients often exhibit signs and symptoms of exhaustion, anorexia, nausea, and hypotension, which can mask the diagnosis of an underlying adrenal insufficiency. In our patient, both the expanding adrenal nodule and immunotherapy induced-adrenalitis likely contributed to the primary adrenal insufficiency, which was confirmed by a cosyntropin stimulation test. Adrenal crisis ensued due to a concomitant secondary adrenal insufficiency from hypophysitis (indicated by the low ACTH) as well as rapid cortisol metabolism brought on by thyroiditis-induced hyperthyroidism. Immunotherapy was likely the culprit of both the hypophysitis and thyroiditis. Identification of the multiple endocrinopathies in our patient enabled prompt treatment and informed future clinical decisions regarding cancer treatment.

Conclusions: Our case demonstrates the significance of retaining adrenal crisis in the differential diagnosis of cancer patients – especially those on immunotherapy – presenting with shock-like symptoms.