title: Paradoxical and atypical responses to pasireotide in aggressive ACTH-secreting pituitary tumors.
abstract: OBJECTIVE
  Pasireotide is the only pituitary targeted medication registered for the treatment of Cushing's disease. Drug efficacy data are largely based on a major prospective study in which the vast majority of patients had microadenomas. The purpose of this study was to summarize results of pasireotide treatment of ACTH secreting macroadenomas from our center.
  
  
  METHODS
  Retrospective review of data extracted from clinical files.
  
  
  RESULTS
  Three patients presented with large and invasive macroadenomas that required several surgical interventions and radiotherapy treatments. Patient 1 is a 57 year-old male who developed an extreme (27-fold) paradoxical response of urinary free cortisol (UFC) levels as measured 2 weeks after pasireotide institution, which increased further (71-fold) in response to dose increment but decreased to baseline levels after treatment interruption. Patient 2 is a 44 year old woman with a long standing (26 years) ACTH-secreting carcinoma metastatic to bone and after bilateral adrenalectomy. After an initial excellent response to pasireotide treatment, ACTH levels escaped suppression and a further rebound was noted 6 weeks after treatment interruption. Patient 3 is a 53 year old man that after escape from temozolomide therapy was started on pasireotide and rapidly responded by almost normalizing UFC excretion after 4 weeks, but returned to baseline UFC levels after four additional weeks of treatment.
  
  
  CONCLUSIONS
  We describe as yet unreported atypical responses to pasireotide treatment in patients with aggressive ACTH-secreting tumors. Increased vigilance is recommended during pasireotide treatment of such patients.
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 64239, Tel Aviv, Israel. yonagr@tlvmc.gov.il.
authors.forename: Yona
authors.identifier: http://orcid.org/0000-0003-4923-488X
authors.initials: Y
authors.lastname: Greenman
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, 64239, Tel Aviv, Israel.
authors.forename: Naftali
authors.initials: N
authors.lastname: Stern
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000188:drug therapy* / Q000378:metabolism; D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; C517782:pasireotide
keywords: Atypical tumor; Cushing’s disease; Paradoxical response; Pasireotide; Pituitary carcinoma