Introduction
Immune check-point inhibitors have revolutionised cancer treatment by improving prognosis but are associated with adverse immune-related side effects (irSEs) such as thyroid dysfunction and hypophysitis. Other endocrine irSEs are less common.
Case Description
A 54-year-old male was started on Ipilimumab (anti-CTLA4 monoclonal antibody) and Nivolumab (PD-1 inhibitor) for metastatic melanoma. After 2 cycles of immunotherapy, he presented with non-ketotic hyperglycaemia and was diagnosed with insulin dependent diabetes. GAD, IA-2 and ZnT8 antibodies were not detected. His admission was complicated by atrial fibrillation with acute thyroiditis. He had mildly elevated thyroid peroxidase and thyroglobulin antibodies. Treatment with Prednisolone was complicated by diabetic ketoacidosis requiring hospital admission. PET CT after 2 cycles of immunotherapy showed reduction in all metastatic lesions. Due to the irSEs, Ipilimumab was ceased but Nivolumab continued. He developed postural dizziness, lethargy, abdominal discomfort with subnormal short Synacthen test, confirming adrenal insufficiency, requiring hydrocortisone replacement. Anti-adrenal antibodies were negative. Normal pituitary MRI and hormones excluded hypophysitis. His acute hyperthyroidism was followed by hypothyroidism requiring thyroxine replacement. After six cycles of immunotherapy with multiple irSEs, he had complete radiological response of metastatic melanoma.
Conclusion
Immune check-point inhibitor therapy is associated with endocrine irSEs; thyroid dysfunction and hypophysitis being the most common. This case demonstrates insulin-dependent diabetes and adrenal insufficiency, rarer forms of irSEs. Novel features included absence of diabetes autoantibodies and anti-adrenal antibodies.
Learning Points
1) Understand the mechanism of action of immune checkpoint inhibitors;
2) Identify endocrinopathies caused by immune checkpoint inhibitors;
3) Understand how to manage immune checkpoint inhibitor related endocrinopathies