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Cortisol Resistance in Man

  • Mortimer B. Lipsett
  • Masako Tomita
  • David D. Brandon
  • Monique M. De Vroede
  • D. Lynn Loriaux
  • George P. Chrousos
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 196)

Abstract

Primary cortisol resistance in man is a familial disease characterized by increased plasma cortisol concentrations, high urinary free cortisol excretion, a normal circadian pattern of cortisol secretion, resistance to adrenal suppression by dexametha­sone and absence of the clinical stigmata of Cushing’s syndrome or signs of adrenal insufficiency. In its severe form, hypertension and hypokalemic alkalosis are present, owing to increased secretion of the sodium-retaining corticoids, corticosterone and deoxycortico­sterone. In subjects with a less severe resistance to cortisol, there are no clinical abnormalities and the disease is revealed only by detailed examination of several parameters of cortisol metabolism or by glucocorticoid receptor studies. In whole-cell glucocorticoid receptor assays (peripheral mononuclear leukocytes, fibroblasts, or B-lymphocytes transformed with the Epstein-Barr Virus) low receptor affinity for dexamethasone could be demon­strated conclusively only in the severely affected subject. When affected cells are transformed with the Epstein-Barr virus, receptor induction is less than that of normal cells. The decreased affinity of the receptor for its ligand is reflected in an increased rate of loss of specific bound ligand during thermal activation. The molecular weight of the receptor, determined by SDS-PAGE, is similar to that from normal cells (~ 92,000). Only in the severely affected patient was the proportion of activated receptor remaining in the cytosol of thermally activated intact cells reduced. At saturating concentrations of dexamethasone, nuclear binding appears normal in cells from both the severe and the asymptomatic forms of this condition, providing an explanation for the apparently complete compensation of the target tissue resistance to glucocorticoids by the high plasma cortisol levels. The clinical manifestations of the disorder (hypertension, hypokalemia) can be corrected with high doses of dexamethasone (3mg/day).

Keywords

Glucocorticoid Receptor Plasma Cortisol Urinary Free Cortisol Mononuclear Leukocyte Serum Corticosterone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Mortimer B. Lipsett
    • 1
  • Masako Tomita
    • 1
  • David D. Brandon
    • 1
  • Monique M. De Vroede
    • 1
  • D. Lynn Loriaux
    • 1
  • George P. Chrousos
    • 1
  1. 1.Developmental Endocrinology Branch, National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaUSA

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