title: Rapid control of severe neoplastic hypercortisolism with metyrapone and ketoconazole.
abstract: BACKGROUND
  Severe Cushing's syndrome elicited by ectopic ACTH syndrome (EAS) or adrenal carcinoma (ACC) can threaten life in the short term. The effectiveness of oral administration of the inhibitors of steroidogenesis ketoconazole and metyrapone in this situation is poorly described.
  
  
  OBJECTIVE
  To report the short-term effectiveness and tolerability of metyrapone and ketoconazole elicited either by EAS or by ACC in patients exhibiting severe hypercortisolism.
  
  
  METHODS
  Retrospective analysis of data obtained for patients with urinary free cortisol (UFC) level estimated to be fivefold the upper limit of the normal range (ULN).
  
  
  METHODS
  A total of 14 patients with EAS and eight with ACC treated in two tertiary-care university hospitals.
  
  
  METHODS
  Metyrapone and ketoconazole treatment in combination (along with symptomatic treatments for co-morbidities).
  
  
  RESULTS
  Evolution of clinically relevant endpoints (blood pressure, kalaemia and glycaemia) and biological intensity of hypercortisolism 1 week and 1 month after starting steroidogenesis inhibition.
  
  
  RESULTS
  After 1 week of treatment, median UFC fell from 40.0 to 3.2 ULN and from 16.0 to 1.0 ULN in patients with EAS and ACC respectively. Median UFC after 1 month of treatment was 0.5 and 1.0 ULN in patients with EAS and ACC respectively and UFC values were normal in 73 and 86% of patients respectively. Clinical status improved dramatically along with kalaemia, glycaemia and blood pressure, allowing a decrease in the relevant treatments.Side effects were minimal and only two patients (one EAS and one ACC) experienced plasma transaminase elevations necessitating ketoconazole withdrawal.
  
  
  CONCLUSIONS
  Metyrapone-ketoconazole combination therapy is well tolerated and provides rapid control of endocrine cancer-related life-threatening hypercortisolism.
authors.affiliation: Department of Nuclear MedicineHaut Lévêque Hospital, F-33604 Pessac, FranceDepartment of EndocrinologyBicêtre Hospital, F-94275 Le Kremlin-Bicêtre, FranceDepartment of EndocrinologyHaut Lévêque Hospital, CHU Bordeaux, F-33604 Pessac, France andDepartment of Nuclear Medicine and OncologyGustave Roussy, F-94800 Villejuif, France.
authors.forename: Jean-Benoît
authors.initials: JB
authors.lastname: Corcuff
authors.affiliation: Department of Nuclear MedicineHaut Lévêque Hospital, F-33604 Pessac, FranceDepartment of EndocrinologyBicêtre Hospital, F-94275 Le Kremlin-Bicêtre, FranceDepartment of EndocrinologyHaut Lévêque Hospital, CHU Bordeaux, F-33604 Pessac, France andDepartment of Nuclear Medicine and OncologyGustave Roussy, F-94800 Villejuif, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Young
authors.affiliation: Department of Nuclear MedicineHaut Lévêque Hospital, F-33604 Pessac, FranceDepartment of EndocrinologyBicêtre Hospital, F-94275 Le Kremlin-Bicêtre, FranceDepartment of EndocrinologyHaut Lévêque Hospital, CHU Bordeaux, F-33604 Pessac, France andDepartment of Nuclear Medicine and OncologyGustave Roussy, F-94800 Villejuif, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Masquefa-Giraud
authors.affiliation: Department of Nuclear MedicineHaut Lévêque Hospital, F-33604 Pessac, FranceDepartment of EndocrinologyBicêtre Hospital, F-94275 Le Kremlin-Bicêtre, FranceDepartment of EndocrinologyHaut Lévêque Hospital, CHU Bordeaux, F-33604 Pessac, France andDepartment of Nuclear Medicine and OncologyGustave Roussy, F-94800 Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
authors.affiliation: Department of Nuclear MedicineHaut Lévêque Hospital, F-33604 Pessac, FranceDepartment of EndocrinologyBicêtre Hospital, F-94275 Le Kremlin-Bicêtre, FranceDepartment of EndocrinologyHaut Lévêque Hospital, CHU Bordeaux, F-33604 Pessac, France andDepartment of Nuclear Medicine and OncologyGustave Roussy, F-94800 Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
authors.affiliation: Department of Nuclear MedicineHaut Lévêque Hospital, F-33604 Pessac, FranceDepartment of EndocrinologyBicêtre Hospital, F-94275 Le Kremlin-Bicêtre, FranceDepartment of EndocrinologyHaut Lévêque Hospital, CHU Bordeaux, F-33604 Pessac, France andDepartment of Nuclear Medicine and OncologyGustave Roussy, F-94800 Villejuif, France antoine.tabarin@chu-bordeaux.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Tabarin
mesh_terms: D000182:ACTH Syndrome, Ectopic / Q000188:drug therapy*; D000310:Adrenal Gland Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D003480:Cushing Syndrome / Q000188:drug therapy* / Q000209:etiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008797:Metyrapone / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007654:Ketoconazole; D008797:Metyrapone