2014, Number 3
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Rev Cuba Endoc 2014; 25 (3)
Glucocorticoid resistance syndrome
Leal CL, Robles TE
Language: Spanish
References: 13
Page: 253-258
PDF size: 71.29 Kb.
ABSTRACT
Glucocorticoids are involved in important biological processes of the body. The
glucocorticoid resistance syndrome or Chrousos's syndrome is a genetic disease
caused by the human glucocorticoid receptor gene mutations. It is characterized by
reduced tissue sensitivity to cortisol and compensatory increase of the
hypothalamus-hypophysis-adrenal axis activity, which leads to a rise of minrealocorticoids, cortisol and adrenal androgens levels. The clinical picture is
variable, going from asymptomatic, mild or severe manifestations to hypertension
and hyperandrogenism. For a right diagnosis, there should be no Cushing-like
manifestations and biochemical hypercortisolism as well as hypothalamushypophysis-
adrenal axis resistance to dexamethasone suppression have to be
proven. The objective of the treatment is to halt the excessive secretion of the
adrenocorticotrope hormone through glucocorticoids that do not present
mineralocorticoid action as it happens with dexamethasone. In the near future,
corrective therapies are expected to be available in order to directly fix genetic
defects in the human glucocorticoid receptor gen.
REFERENCES
Kino T, Chrousos GP. Glucocorticoid effects on gene expression. In: Steckler T, Kalin NH, Reul JMHM eds. Handbook of Stress and the Brain. Amsterdam: Elsevier; 2005. p. 295-311.
Chrousos GP, Charmandari E, Kino T. Glucocorticoid action networks – an introduction to systems biology. J Clin Endocrinol Metab. 2004;89:563-4.
Charmandari E. Primary Generalized Glucocorticoid Resistance and Hypersensitivity. Horm Res Paediatr. 2011;76:145-55.
Charmandari E. Primary Generalized Glucocorticoid Resistance and Hypersensitivity: The End-Organ Involvement in the Stress Response. Sci Signal. 2012;5:5.
Hsu SC, De Franco DB. Selectivity of cell cycle regulation of glucocorticoid receptor function. J Biol Chem. 1995;270(7):3359-64.
Van Rossum EF, Lamberts SW. Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition. Recent Prog Horm Res. 2004;59:333-57.
Ruiz M. The glucocorticoid receptor as a regulator of cortisol responses in cortisol resistant patients and healthy subjects [tesis doctoral]. Stockholm. Karolinska Institutet; 2013.
Vingerhoeds ACM, Thijssen JHH, Schwarts F. Spontaneous hypercortisolism without Cushing’s syndrome. J Clin Endocrinol Metab. 1976;43:1128-33.
Chrousos GP, Vingerhoeds A, Brandon D, Eil C, Pugeat M, DeVroede M, et al. Primary cortisol resistance in man: a glucocorticoid receptor-mediated disease. J Clin Invest. 1982;69:1261-9.
Chrousos GP, Detera-Wadleigh SD, Karl M. Syndromes of glucocorticoid resistance. Ann Intern Med. 1993;119:1113-24.
Charmandari E, Kino T. Chrousos syndrome: a seminal report, a phylogenetic enigma and the clinical implications of glucocorticoid signalling changes. Eur J Clin Invest. 2010;40:932-42.
Chrousos G. Primary generalized glucocorticoid resistance. BMC Medicine. 2011;9:27.
McMahon SK, Pretorius CJ, Ungerer JP, Salmon NJ, Conwell LS, Pearen MA, et al. Neonatal complete generalized glucocorticoid resistance and growth hormone deficiency caused by a novel homozygous mutation in helix 12 of the ligand binding domain of the glucocorticoid receptor gene (NR3C1). J Clin Endocrinol Metab. 2010;95:297-302.