title: Managing hyperglycemia in patients with Cushing's disease treated with pasireotide: medical expert recommendations.
abstract: To recommend an approach to monitoring and treating hyperglycemia in pasireotide-treated patients with Cushing's disease, a severe clinical condition caused by a pituitary adenoma hypersecreting adrenocorticotropic hormone. Advisory Board meeting of ten European experts in pituitary disease and diabetes mellitus in Munich, Germany, on February 23, 2012, to obtain expert recommendations. Cushing's disease presents a number of management challenges. Pasireotide, a novel agent for the treatment of Cushing's disease with proven biochemical and clinical efficacy, improves outcomes and expands treatment options. Clinical trials have shown that the pasireotide adverse event profile is similar to that of other somatostatin analogs, except for a higher frequency of hyperglycemia. Mechanistic studies in healthy volunteers suggest that pasireotide-associated hyperglycemia is due to reduced secretion of glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide, and insulin; however, it is associated with intact postprandial glucagon secretion. Individual patients' results demonstrate effective hyperglycemia management by following standard guidelines for the treatment of diabetes mellitus with individual adaptation to the specific underlying pathophysiology, i.e., preferential use of GLP-1 based-medications. Patients on pasireotide treatment should be monitored for changes in glucose metabolism and hyperglycemia. Diabetes mellitus should be managed by initiation of medical therapy with metformin and staged treatment intensification with a dipeptidyl peptidase-4 inhibitor, with a switch to a GLP-1 receptor agonist and initiation of insulin, as required, to achieve and maintain glycemic control. Further research into hyperglycemia following pasireotide treatment will help refine the optimal strategy in Cushing's disease.
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, Naples, Italy, colao@unina.it.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Christophe
authors.initials: C
authors.lastname: De Block
authors.forename: Maria Sonia
authors.initials: MS
authors.lastname: Gaztambide
authors.forename: Sudhesh
authors.initials: S
authors.lastname: Kumar
authors.forename: Jochen
authors.initials: J
authors.lastname: Seufert
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy*; D018027:Receptors, Glucagon / Q000819:agonists / Q000378:metabolism; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007328:Insulin; D018027:Receptors, Glucagon; D013004:Somatostatin; D008687:Metformin; C517782:pasireotide
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