Slowly Progressive Secondary Adrenal Insufficiency Due to Pembrolizumab Administration in a Patient With a History of Pituitary Neuroendocrine Tumor

A 70-year-old man developed anorexia, general malaise, and hyponatremia with a serum sodium level of 120 mEq/L after the fifth cycle of pembrolizumab administration for bladder cancer. A rapid adrenocorticotropic hormone (ACTH) loading test result was within the normal range (basal and peak cortisol levels of 8.2 μg/dL and 20.0 μg/dL, respectively), and his serum sodium level recovered by salt loading. However, about two weeks later, his anorexia and malaise worsened, and his serum sodium level decreased to 122 mEq/L. A rapid ACTH loading test performed again four weeks after the first test showed a peak cortisol level of 13.4 μg/dL, and a corticotropin-releasing hormone (CRH) loading test showed basal ACTH and cortisol levels of 19 pg/mL and 6.3 μg/dL and peak levels of 34 pg/mL and 8.7 μg/dL, respectively. Therefore, secondary adrenal insufficiency (SAI) was diagnosed. Although he underwent nonfunctioning pituitary neuroendocrine tumor resection at the age of 55 years, the tumor was not significantly different from the postoperative findings. The possible cause of SAI was ACTH deficiency after pembrolizumab administration. Four months after diagnosis, the basal ACTH and cortisol levels had decreased from 19 to 17 pg/mL and from 6.0 to 3.2 μg/dL, respectively. We were able to follow the atypical, slowly progressive course of SAI due to pembrolizumab.