Abstract
Abstract Introduction Immune checkpoint inhibitors (ICI) have been approved for use in cancer therapy for malignant melanoma, non-small cell lung cancer, and renal cell carcinoma in the last decade. Since their inception, immune-related adverse events (irAEs) have been well documented. We present a patient who developed 2 irAEs - grade 1 irAE during therapy and grade 3 irAE five months after completion of anti-CTLA-4 (Ipilimumab) and anti-PD-1 antibody (Nivolumab) therapy. Case description Our patient is a 65-year-old woman who was diagnosed in 2019 with Melanoma over the left knee which was resected in her home country. During follow-up here, she was started on immunotherapy with Ipilimumab and Nivolumab for metastatic disease. Her baseline labs including TFTs were normal before initiation of therapy. During treatment after 4 infusions, she developed hypothyroidism. At that time she was tolerating treatment well. Levothyroxine was initiated for this grade 1 irAE with the continuation of immunotherapy. She decided to move to her home country with a plan to pursue further immunotherapy upon her return. 7 months after discontinuation of therapy, the patient presented to our hospital with nausea, vomiting, and dizziness for 2 months. She was hypotensive and minimally responsive to intravenous fluids. Labs drawn were remarkable for hypothyroidism. Further workup demonstrated adrenal insufficiency with morning cortisol of 0.1 μg/dL and ACTH of <1.5 pg/ml. Pituitary hormones were within normal range except for elevated prolactin. A contrast-enhanced MRI of the pituitary was negative for any enlargement or mass. She was diagnosed with secondary adrenal insufficiency and managed with stress-dose corticosteroids with a resolution of symptoms. We were able to ascertain that our patient developed grade 3 irAE almost 5 months after her last immunotherapy. Discussion Cancer immunotherapy is associated with endocrinopathies such as hypophysitis, hypothyroidism, and adrenal insufficiency. As per a review done by González-Rodríguez E et al it has been found that the median time of onset from initiation for endocrine AEs was 7 - 20 weeks due to Ipilimumab and 11 weeks due to Nivolumab. In patients who received combined therapy, as per a retrospective study done by Nguyen et al, the median time from ICI administration to the diagnosis of immune-related hypophysitis was 35.8 weeks. In 2019, Ohara N reported a case of a patient with lung adenocarcinoma who developed isolated ACTH deficiency 4 months after discontinuation of Nivolumab therapy. Our patient developed two irAEs - during and after completion of immunotherapy. Symptoms can often be generalized and overlap with those of cancer progression making it difficult to diagnose. Our case highlights the need for continued surveillance of these patients by physicians probably even months after completion. Presentation: No date and time listed
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