Abdominal pain as an initial symptom of isolated ACTH deficiency induced by nivolumab in a patient with malignant mesothelioma

Used for a wide range of cancers, nivolumab has been reported to cause immune-related adverse events, including isolated adrenocorticotropic hormone deficiency (IAD). We report an 81-year-old woman with malignant mesothelioma who presented with abdominal pain after eight courses of nivolumab therapy, leading to the diagnosis of nivolumab-induced IAD. We should consider adrenal insufficiency (AI) when a patient on nivolumab complains of abdominal pain and has no other explanatory findings. Infusion-resistant hypotension and hyponatraemia can further suggest AI.

Pembrolizumab- and ipilimumab-induced diabetic ketoacidosis and isolated adrenocorticotropic hormone deficiency: a case report

Background Several human monoclonal antibodies directed against immune checkpoints, including T lymphocyte antigen 4 and programmed cell death protein 1, have been implemented for cancer treatment in order to promote effector T cell response to tumors. Despite the antitumor activity of these agents, a significant number of patients demonstrated immune-related adverse events that affected the functions of multiple organs, including the endocrine system. We report the first case of immune checkpoint inhibitor–induced simultaneous diabetic ketoacidosis and isolated adrenocorticotropic hormone deficiency following combination treatment with immune checkpoint inhibitors. Case presentation A 70-year-old Thai man with no previous history of diabetes mellitus was diagnosed with stage IVB non–small cell lung with pleural and liver metastases. After 14 weeks of combination treatment with pembrolizumab and ipilimumab, he presented with fatigue, nausea, and vomiting. Laboratory investigation revealed random plasma glucose 794 mg/dl, serum ketone 6.3 mmol/L, bicarbonate 13 mmol/L, and high anion gap 24 mmol/L. New-onset diabetes mellitus and diabetic ketoacidosis were diagnosed. Insulin therapy was initiated a favorable outcome within 10 hours. Despite improvement of hyperglycemia, the patient had persistent nausea and hyponatremia. Further investigation revealed cortisol 0.8 μg/dl and adrenocorticotropic hormone 21.7 pg/ml. His other pituitary hormone levels were normal, except for mild elevation of gonadotropin hormone. Magnetic resonance imaging of the pituitary showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, resulting in an improvement of his symptoms. Conclusion Our patient developed new-onset diabetes mellitus, diabetic ketoacidosis, and isolated adrenocorticotropic hormone deficiency during cancer treatment with pembrolizumab and ipilimumab. The present case highlights the need for physicians to be aware that immune-related adverse events can occur in multiple organs at the same time.

A Case of Isolated Adrenocorticotropic Hormone Deficiency Caused by Pembrolizumab

Pembrolizumab (Keytruda®) is an anti-programmed cell death 1-specific monoclonal antibody that has become the standard second-line chemotherapy for unresectable advanced microsatellite instability-high colorectal cancer. Several immune-related adverse events (irAEs), particularly endocrinopathy, are linked to the administration of pembrolizumab. We report here a case of pembrolizumab-induced isolated adrenocorticotropic hormone deficiency in a patient with metastatic colon cancer. A 65-year-old woman visited our hospital for complaints of fatigue with a recent history of primary resection of cecal mucinous cancer and hepatectomy for liver metastasis 3 years ago. Peritoneal dissemination was detected 2 years after surgery. Several chemotherapeutic regimens of cytotoxic and molecular targeted drugs were administered; however, the metastases progressed gradually. Pembrolizumab monotherapy was started because of resistance to treatment. After 2 cycles of pembrolizumab, the patient was severely fatigued. Laboratory data demonstrated that the cortisol level was extremely low. All the other values were within the normal range. Magnetic resonance imaging indicated no mass in the pituitary gland. From multiple tolerance tests, we diagnosed isolated adrenocorticotropic hormone deficiency caused by pembrolizumab. The patient’s symptoms improved promptly with cortisol treatment. An abdominal contrast-enhanced computed tomography scan after 5 cycles of pembrolizumab demonstrated that the size of the peritoneal dissemination remained unchanged. However, her serum level of carcinoembryonic antigen had decreased to normal levels. Endocrine disorders are very rarely seen as irAEs. Careful laboratory data follow-up is required to inhibit the progression of severe endocrine disorders.