A 56-year-old woman with metastatic melanoma receiving ipilimumab and nivolumab every 3 weeks developed headaches during the course of her treatment. In the week following her first treatment, the patient reported a few mild morning headaches that improved with acetaminophen. After receiving 3 cycles of ipilimumab, 3 mg/kg, and nivolumab, 1 mg/kg, and 8 weeks after her first treatment, the patient reported experiencing daily headaches for at least the prior week and a half. The location of her headaches varied, and there was no associated eye or temple pain. At best, with taking nonsteroidal anti-inflammatory drugs, the headache decreased to pain rated 3 on a scale of 1 to 10. Also at this time, the patient reported low energy levels and difficulty reading; however, physical examination showed no gross visual field defects. Laboratory workup conducted 8 weeks after initiating treatment included adrenocorticotropic hormone (ACTH) and cortisol levels that were measured at 25 pg/mL (reference range, 10-60 pg/mL) and 16.8 μg/dL (reference range, 6-24 μg/dL), respectively. Thyroid-stimulating hormone (TSH) level was 0.82 mIU/L (reference range, 0.5-5.0 mIU/L), which was gradually decreasing compared with 1.41 mIU/L 5 weeks earlier and 1.21 mIU/L 2 weeks earlier. Her total triiodothyronine level was measured at 73 ng/dL (reference range, 80-200 ng/dL) and free thyroxine level was 1.0 ng/dL (reference range, 0.9-1.7 ng/dL). Her serum sodium level was measured at 138 mEq/L; 1 week later it was measured at 135 mEq/L (reference range, 135-145 mEq/L). Contrast-enhanced magnetic resonance imaging (MRI) of the brain was performed for further assessment (Figure).