title: Hypophysitis caused by ipilimumab in cancer patients: hormone replacement or immunosuppressive therapy.
abstract: Ipilimumab is besides the BRAF inhibitor vemurafenib the first officially approved medical treatment for metastatic melanoma, which results in improved survival. Ipilimumab leads to a release of a CTLA4-mediated inhibition of T-cell immunoreactions. Therefore, patients may also suffer from immune-related adverse events affecting different organs, which are typically treated by high-dose corticosteroids. Ipilimumab-induced hypophysitis (iH) has been reported in up to 17% of melanoma patients in clinical trials.Here we present 5 patients with metastatic melanoma and 2 patients with prostate cancer who developed hypophysitis after ipilimumab therapy. Patients were treated by high-dose corticosteroid therapy resulting in the resolution of local inflammation but not of pituitary deficiencies. Partial or complete hypopituitarism remained in all patients. Pharmacotherapy with high-dose corticosteroids caused complications in 5 patients, necessitating hospitalization in 4. 2 of the 3 patients with progressive disease died, while 3 patients had stable disease and 1 patient showed tumor regression after discontinuation of ipilimumab.In summary, with regard to safety and simplicity of hormonal substitution therapy we have to scrutinize high-dose corticosteroid therapy, though it only improves inflammation but not neuro-endocrine function and may cause further morbidity. Regression of the tumor depends on the ipilimumab-mediated immune events, in which high-dose and long-term corticosteroid therapy for iH appears to be counter-intuitive. Herein, we discuss screening and the diagnostic as well as therapeutic management of iH in metastatic cancer patients from an endocrinologic perspective.
authors.affiliation: Fifth Medical Clinic, University Medical Center Mannheim, Mannheim, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Lammert
authors.forename: H J
authors.initials: HJ
authors.lastname: Schneider
authors.forename: T
authors.initials: T
authors.lastname: Bergmann
authors.forename: U
authors.initials: U
authors.lastname: Benck
authors.forename: B K
authors.initials: BK
authors.lastname: Krämer
authors.forename: R
authors.initials: R
authors.lastname: Gärtner
authors.forename: C
authors.initials: C
authors.lastname: Metzner
authors.forename: C
authors.initials: C
authors.lastname: Schöfl
authors.forename: C
authors.initials: C
authors.lastname: Berking
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D000074324:Ipilimumab; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010900:Pituitary Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging*; D011859:Radiography
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D000074324:Ipilimumab