Pembrolizumab-Induced Hypophysitis in the Setting of Renal Cell Carcinoma

Immune checkpoint inhibitors (ICIs) like pembrolizumab have revolutionized oncology but are associated with immune-related adverse events, including rare cases of hypophysitis. Pembrolizumab-induced hypophysitis typically presents as an isolated adrenocorticotropic hormone (ACTH) deficiency. However, atypical cases with panhypopituitarism and pituitary enlargement have been reported. Here, we describe a unique case of delayed-onset pembrolizumab-induced hypophysitis in a patient with renal cell carcinoma, highlighting the need for continued vigilance in recognizing endocrine complications even months after therapy cessation. A 55-year-old female with renal cell carcinoma, treated with left nephrectomy and pembrolizumab, presented with weakness, orthostatic hypotension, nausea, and vomiting. She had undergone multiple prior evaluations without a clear diagnosis. On admission, hypoglycemia and hypotension raised suspicion for adrenal insufficiency. Initial endocrine testing revealed low AM cortisol and ACTH levels, suggesting central adrenal insufficiency. A cosyntropin stimulation test confirmed the diagnosis. MRI of the sella showed no pituitary mass but was positive for hypophysitis, attributed to her prior pembrolizumab therapy. The patient was treated with hydrocortisone, resulting in symptom relief. This case highlights a rare instance of hypophysitis secondary to pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, in a patient with renal cell carcinoma. While thyroid dysfunction is more common with ICIs, hypophysitis remains an uncommon complication, especially with anti-PD-1 agents. Our patient's late presentation, nearly five months after the conclusion of treatment, suggests lasting effects of pembrolizumab on the hypothalamic-pituitary system.