title: Up-to 5-year efficacy of pasireotide in a patient with Cushing's disease and pre-existing diabetes: literature review and clinical practice considerations.
abstract: OBJECTIVE
  Pasireotide is a multi-receptor-targeted somatostatin analogue approved in the EU and in the US for the treatment of adults with Cushing's disease (CD). Pasireotide has a safety profile similar to other somatostatin analogues with the exception of hyperglycemia. In this report and literature review, the current understanding of predicting a positive treatment response to pasireotide in CD and the management of diabetes mellitus (DM) during pasireotide treatment are discussed and analyzed.
  
  
  METHODS
  We report a case of a 55-year-old woman with CD and DM who benefitted from long-term pasireotide. The patient, who was enrolled in a phase III trial of the drug, showed early clinical improvements with pasireotide [900 μg subcutaneously twice daily (bid)] but was classified as a non-responder as urinary free cortisol (UFC) levels, were not normalized. Continuation of pasireotide for 12 months at an increased dose (1,200 μg bid) normalized UFC levels and restored cortisol rhythm. The initial deterioration in her blood glucose was managed with insulin and metformin; however, after 12 months' treatment with pasireotide her DM was well controlled with oral hypoglycemic agents. Five years later, the patient is still receiving pasireotide (300 μg bid) with no loss of clinical or biochemical efficacy and with continued glycemic control.
  
  
  CONCLUSIONS
  This case presentation indicates that uncontrolled UFC levels during the first few months of pasireotide treatment as well as worsening of glycemic control in patients with CD and DM are not always predictive of the efficacy and tolerability and appears to support the long-term continuation of pasireotide.
authors: Division of Endocrinology, Polytechnic University of Marche, Via Conca 71, 60020, Torrette de Ancona, AN, Italy.
authors: Laura
authors: L
authors: Trementino
authors: Marina
authors: M
authors: Cardinaletti
authors: Carolina
authors: C
authors: Concettoni
authors: Giorgia
authors: G
authors: Marcelli
authors: Marco
authors: M
authors: Boscaro
authors: Giorgio
authors: G
authors: Arnaldi
mesh_terms: D000284:Administration, Oral; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D017326:Clinical Trials, Phase III as Topic; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007279:Injections, Subcutaneous; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000175:diagnosis / Q000188:drug therapy* / Q000652:urine; D016032:Randomized Controlled Trials as Topic; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D013004:Somatostatin; C517782:pasireotide; D006854:Hydrocortisone