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  • Title: Strategies for the characterization of disorders in cortisol sensitivity.
    Author: Russcher H, Smit P, van Rossum EF, van den Akker EL, Brinkmann AO, de Heide LJ, de Jong FH, Koper JW, Lamberts SW.
    Journal: J Clin Endocrinol Metab; 2006 Feb; 91(2):694-701. PubMed ID: 16317053.
    Abstract:
    CONTEXT: The clinical presentation of abnormalities in glucocorticoid (GC) sensitivity is diverse, and therefore it is difficult to diagnose this condition. OBJECTIVE AND DESIGN: The objective of the study was to develop strategies for the characterization of GC sensitivity disorders. SETTING: The study was conducted in an outpatient clinic. PATIENTS: Nine patients with GC sensitivity disorders participated. INTERVENTIONS: 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. CONCLUSION: 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.
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