title: Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series.
abstract: BACKGROUND
  Ipilimumab (Yervoy; Bristol-Myers Squibb) is a novel fully humanised monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4, an immune checkpoint molecule, to augment anti-tumour T-cell responses. It is associated with significant immune-related side-effects including hypophysitis.
  
  
  OBJECTIVE
  We reviewed the clinical and biochemical characteristics of 10 patients with ipilimumab-induced hypophysitis (IH), and developed guidelines for the early detection and management of IH based on our experiences at three major teaching hospitals in Sydney.
  
  
  METHODS
  All patients were evaluated at the Crown Princess Mary Cancer Centre and Department of Endocrinology, Westmead Hospital, Department of Endocrinology, Royal Prince Alfred Hospital, the Melanoma Institute Australia and Macarthur Cancer Therapy Centre, Campbelltown Hospital from 2010 to 2014. Relevant data were extracted by review of medical records. Main outcome measures included clinical features, hormone profile and radiological findings associated with IH, and presence of pituitary recovery.
  
  
  RESULTS
  Ten patients were identified with IH. In four patients who underwent monitoring of plasma cortisol, there was a fall in levels in the weeks prior to presentation. The pituitary-adrenal and pituitary-thyroid axes were affected in the majority of patients, with the need for physiological hormone replacement. Imaging abnormalities were identified in five of 10 patients, and resolved without high-dose glucocorticoid therapy. To date, all patients remain on levothyroxine and hydrocortisone replacement, where appropriate.
  
  
  CONCLUSIONS
  There is significant morbidity associated with development of IH. We suggest guidelines to assist with early recognition and therapeutic intervention.
authors.affiliation: Department of Diabetes and Endocrinology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Lam
authors.affiliation: Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.|Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|Central Coast Cancer Centre, Gosford Hospital, Gosford, New South Wales, Australia.
authors.forename: M M K
authors.initials: MM
authors.lastname: Chan
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: A N
authors.initials: AN
authors.lastname: Sweeting
authors.affiliation: Department of Endocrinology, St Vincent's Hospital, Sydney, New South Wales, Australia.|Hormones and Cancer Group, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: S M C
authors.identifier: http://orcid.org/0000-0003-0127-6482
authors.initials: SM
authors.lastname: De Sousa
authors.affiliation: Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.|Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Clements
authors.affiliation: Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.|Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|Melanoma Institute of Australia, Sydney, New South Wales, Australia.
authors.forename: M S
authors.initials: MS
authors.lastname: Carlino
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|Melanoma Institute of Australia, Sydney, New South Wales, Australia.
authors.forename: G V
authors.initials: GV
authors.lastname: Long
authors.affiliation: Department of Endocrinology, St Vincent's Hospital, Sydney, New South Wales, Australia.|Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Tonks
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Chua
authors.affiliation: Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.|Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.|Melanoma Institute of Australia, Sydney, New South Wales, Australia.|Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: R F
authors.initials: RF
authors.lastname: Kefford
authors.affiliation: Department of Diabetes and Endocrinology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.|Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: D R
authors.initials: DR
authors.lastname: Chipps
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D001315:Australia; D060908:CTLA-4 Antigen / Q000276:immunology; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007018:Hypopituitarism / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy; D007167:Immunotherapy; D000074324:Ipilimumab; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D060908:CTLA-4 Antigen; D000074324:Ipilimumab
keywords: hypophysitis; hypopituitarism; immune-related adverse event; immunotherapy; ipilimumab; melanoma