title: Strategies for the characterization of disorders in cortisol sensitivity.
abstract: BACKGROUND
  The clinical presentation of abnormalities in glucocorticoid (GC) sensitivity is diverse, and therefore it is difficult to diagnose this condition.
  
  
  OBJECTIVE
  The objective of the study was to develop strategies for the characterization of GC sensitivity disorders.
  
  
  METHODS
  The study was conducted in an outpatient clinic.
  
  
  METHODS
  Nine patients with GC sensitivity disorders participated.
  
  
  METHODS
  Sequence analysis of the GC receptor (GR), determination of GR number per cell, GR ligand-binding affinity, and GR splice regulation were performed in freshly prepared peripheral blood mononuclear lymphocytes and Epstein-Barr virus-transformed lymphoblasts. Cellular GC sensitivity was determined ex vivo by measuring the effect of dexamethasone on GC-induced leucine-zipper and IL-2 mRNA levels and on cell proliferation.
  
  
  RESULTS
  Differences in GR number per cell, GR affinity, GR splice variants, and effects on transactivation or transrepression of GC-sensitive genes were observed between patients and controls. Epstein-Barr virus transformation of lymphoblasts had no influence on GR affinity but increased the GR number 5-fold in healthy controls. In patients diagnosed as cortisol resistant, however, GR number after transformation was increased significantly less than 5-fold, whereas a higher GR number was observed in a patient suspected of cortisol hypersensitivity.
  
  
  CONCLUSIONS
  This study illustrates several strategies to define abnormalities in GC sensitivity by describing nine patients with affected GC sensitivity, all with a unique clinical course and background.
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Russcher
authors.forename: Pauline
authors.initials: P
authors.lastname: Smit
authors.forename: Elisabeth F C
authors.initials: EF
authors.lastname: van Rossum
authors.forename: Erica L T
authors.initials: EL
authors.lastname: van den Akker
authors.forename: Albert O
authors.initials: AO
authors.lastname: Brinkmann
authors.forename: Loek J M
authors.initials: LJ
authors.lastname: de Heide
authors.forename: Frank H
authors.initials: FH
authors.lastname: de Jong
authors.forename: Jan W
authors.initials: JW
authors.lastname: Koper
authors.forename: Steven W J
authors.initials: SW
authors.lastname: Lamberts
mesh_terms: D000293:Adolescent; D000303:Adrenal Cortex Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D004247:DNA; D006854:Hydrocortisone