title: Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma.
abstract: BACKGROUND
  Ipilimumab (Ipi) is approved by the Food and Drug Administration for the treatment of unresectable or metastatic melanoma. Little is known about Ipi-induced hypophysitis (IH), an important treatment complication.
  
  
  OBJECTIVE
  The objectives of the study were as follows: 1) to examine the prevalence of IH, 2) to characterize the clinical course and treatment outcomes in IH, 3) to identify the risk factors for the development of IH, and 4) to determine optimal strategies for the management of IH.
  
  
  METHODS
  This was a retrospective review.
  
  
  METHODS
  The study was conducted at a tertiary referral center.
  
  
  METHODS
  One hundred fifty-four adult patients with metastatic melanoma were evaluated at Massachusetts General Hospital and were treated with Ipi between March 2008 and December 2013.
  
  
  METHODS
  The intervention included treatment with Ipi.
  
  
  METHODS
  Pituitary magnetic resonance imaging, pituitary hormone assessment, and patient survival were measured.
  
  
  RESULTS
  IH was diagnosed in 17 patients (11%). Male gender (P = .02) and older age (P = .005), but not the cumulative dose of Ipi, were risk factors for IH. All patients with IH had anterior hypopituitarism (none had diabetes insipidus). Hypopituitarism was persistent in most individuals (76%). Diffuse pituitary enlargement was observed exclusively in all cases of IH and, upon retrospective review of magnetic resonance imaging scans, this finding preceded the clinical diagnosis of hypophysitis in eight patients. Pituitary enlargement resolved rapidly (within 40 d in seven of seven patients). Median survival in patients with IH was 19.4 vs 8.8 months (P = .05) in the remainder of the cohort.
  
  
  CONCLUSIONS
  Male gender and older age are risk factors for IH. Pituitary enlargement is sensitive and specific for IH in the appropriate setting, can precede the clinical diagnosis, and resolves rapidly. Anterior pituitary function recovery is uncommon. The incidence of hypophysitis may positively predict survival in melanoma patients treated with Ipi.
authors: Neuroendocrine Unit (A.T.F., N.A.T., A.K., L.N.), Massachusetts General Hospital and Harvard Medical School, and Center for Melanoma (R.S., D.L., R.F.), Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114.
authors: Alexander T
authors: AT
authors: Faje
authors: Ryan
authors: R
authors: Sullivan
authors: Donald
authors: D
authors: Lawrence
authors: Nicholas A
authors: NA
authors: Tritos
authors: Riley
authors: R
authors: Fadden
authors: Anne
authors: A
authors: Klibanski
authors: Lisa
authors: L
authors: Nachtigall
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007018:Hypopituitarism / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D000074324:Ipilimumab; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D010902:Pituitary Gland / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab