title: Prevalence of hypophysitis in a cohort of patients with metastatic melanoma and prostate cancer treated with ipilimumab.
abstract: OBJECTIVE
  Ipilimumab is a human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4, that has been shown to significantly improve survival in patients with metastatic melanoma. Blocking cytotoxic T-lymphocyte antigen-4 elicits T cell activation, proliferation and anti-tumor response, but can also trigger immune-related adverse events. Among immune-related endocrinopathies, hypophysitis represents the most frequent, with an incidence up to 17% in patients treated with ipilimumab.
  
  
  METHODS
  We report nine cases of ipilimumab-induced hypophysitis in a cohort of 273 patients treated with ipilimumab between 2006 and 2015, as part of clinical trials or after its marketing. Thyroid function tests were scheduled at screening and during follow up (every 21 days) in all patients. Cortisol, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing hormone, and estradiol (for females) or testosterone (for males), prolactin, growth hormone, insulin-like growth factor 1 were measured only in case of clinical suspicion.
  
  
  RESULTS
  The incidence of hypophysitis was 3.3%. The most frequent pituitary failure was adrenocorticotropic hormone and thyroid stimulating hormone secretion with a complete recovery of thyroid stimulating hormone, but not of adrenocorticotropic hormone during follow up. All patients had negative pituitary antibodies. The main symptoms at diagnosis were fatigue and headache.
  
  
  CONCLUSIONS
  Clinicians should be aware about the risk of hypophysitis during treatment with immune check-point inhibitors and the necessity of investigating pituitary function during therapy. Pituitary magnetic resonance imaging does not seem pivotal for a definite diagnosis if not performed at the onset of disease.
authors.affiliation: Section of Endocrinology, Department of Medical, Surgical and Neurological sciences, University of Siena, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Brilli
authors.affiliation: Medical Oncology and Immunotherapy Unit, Department of Oncology, Istituto Toscano Tumori, University of Siena, Siena, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Danielli
authors.affiliation: Section of Endocrinology, Department of Medical, Surgical and Neurological sciences, University of Siena, Siena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ciuoli
authors.affiliation: Medical Oncology and Immunotherapy Unit, Department of Oncology, Istituto Toscano Tumori, University of Siena, Siena, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Calabrò
authors.affiliation: Medical Oncology and Immunotherapy Unit, Department of Oncology, Istituto Toscano Tumori, University of Siena, Siena, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Giacomo
authors.affiliation: Unit of Neuroimaging and Neurointervention, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cerase
authors.affiliation: Section of Endocrinology, Department of Medical, Surgical and Neurological sciences, University of Siena, Siena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Paffetti
authors.affiliation: Section of Endocrinology, Department of Medical, Surgical and Neurological sciences, University of Siena, Siena, Italy.
authors.forename: Fausta
authors.initials: F
authors.lastname: Sestini
authors.affiliation: Department of Medical Biotechnologies, Biochemistry Division, University of Siena, UOC Laboratorio Patologia Clinica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Brunetta
authors.initials: B
authors.lastname: Porcelli
authors.affiliation: Medical Oncology and Immunotherapy Unit, Department of Oncology, Istituto Toscano Tumori, University of Siena, Siena, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.affiliation: Section of Endocrinology, Department of Medical, Surgical and Neurological sciences, University of Siena, Siena, Italy. pacini8@unisi.it.
authors.forename: Furio
authors.initials: F
authors.lastname: Pacini
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D017668:Age of Onset; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000072659:Hypophysitis / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology*; D000074324:Ipilimumab / Q000009:adverse effects* / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000150:complications* / Q000188:drug therapy; D008875:Middle Aged; D010901:Pituitary Function Tests; D015995:Prevalence; D011471:Prostatic Neoplasms / Q000150:complications* / Q000188:drug therapy; D013972:Thyrotropin / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D000074324:Ipilimumab; D000324:Adrenocorticotropic Hormone; D013972:Thyrotropin
keywords: CTLA-4; Hypophysitis; Ipilimumab; Melanoma