Autoimmune hypophysitis in a patient successfully treated with anti-ctla-4 (Ipilimumab) immunotherapy for metastatic malignant melanoma

A 72-year-old man who had received four cycles of the anti-cy-totoxic T-lymphocyte antigen-4 (CTLA-4) ipilimumab 1 for advanced metastatic melanoma, presented with a rapid deterioration in mental state, deranged serum electrolytes, abnormal thyroid function and evidence of diabetes insipidus. Serum biochemistry and brain imaging raised the possibility of immune-mediated hypopituitarism related to ipilimumab. After failure to respond to therapy, active treatment was withdrawn. Methods The post-mortem findings are reported, with emphasis on the pituitary histopathology, including immunohistochemical elucidation of the inflammatory infiltrate. Results Near total loss of anterior pituitary endocrine tissue and patchy chronic inflammatory involvement of the neurohypophysis, consistent with infundibulo-panhypophysitis. 2,3 Notably there was no residual melanoma identified in the sites suspicious on pretreat-ment imaging of metastases. Discussion Auto-immune hypophysitis is a rare immune-mediated adverse event associated with administration of ipilimumab 2,4–6 used in the treatment of advanced melanoma. 7–9 Trials suggest that autoimmune hypophysitis may occur in up to 17% of treated pa-tients. 2 Generally, patients are diagnosed on imaging and show a clinical-radiological response to steroids and hormone replacement therapy, and biopsy is not performed. 2,4,8,9 This case offers a rare opportunity to examine the histology of infundibulopanhypophy-sitis after treatment with the anti-CTLA-4 antibody ipilimumab.