Transient generalized glucocorticoid hypersensitivity

Nicolas C. Nicolaides, Agaristi Lamprokostopoulou, Alexandros Polyzos, Tomoshige Kino, Eleni Katsantoni, Panagiota Triantafyllou, Athanasios Christophoridis, George Katzos, Maria Dracopoulou, Amalia Sertedaki, George P. Chrousos, Evangelia Charmandari

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Transient generalized glucocorticoid hypersensitivity is a rare disorder characterized by increased tissue sensitivity to glucocorticoids and compensatory hypo-activation of the hypothalamic-pituitary-adrenal axis. The condition itself and the underlying molecular mechanisms have not been elucidated. Objective: To present the clinical manifestations, endocrinologic evaluation and transcriptomic profile in a patient with transient generalized glucocorticoid hypersensitivity. Design and Results: A 9-year-old girl presented with an 8-month history of clinical manifestations suggestive of Cushing syndrome. Endocrinologic evaluation revealed undetectable 08:00 h ACTH (<1 pg/mL) and cortisol (0·025 μg/dL) concentrations, which remained decreased throughout the 24-h period and did not respond to stimulation with ovine CRH. The disease gradually resolved spontaneously over the ensuing 3 months. Sequencing of the human glucocorticoid receptor gene revealed no mutations or polymorphisms. Western blot analysis in peripheral blood mononuclear cells revealed equal protein expression of hGRα of the patient in the disease and postresolution phases compared with a control subject. Transcriptomic analysis in peripheral blood mononuclear cells in the disease and postresolution phases identified 903 differentially expressed genes. Of these, 106 genes were up-regulated and 797 were down-regulated in the disease compared with the resolution phase. Bioinformatics analysis on the differentially expressed gene networks revealed Nuclear Factor-κB as the predominant transcription factor influencing the expression of the majority of differentially expressed genes. Conclusions: Our findings indicate that a transient postreceptor defect, or a virus- or bacterium-encoded molecule, may have enhanced glucocorticoid signal transduction, leading to transient generalized glucocorticoid hypersensitivity and hypo-activation of the HPA axis.

Original languageEnglish
Pages (from-to)1306-1315
Number of pages10
JournalEuropean Journal of Clinical Investigation
Volume45
Issue number12
DOIs
Publication statusPublished - 1 Dec 2015
Externally publishedYes

Fingerprint

Glucocorticoids
Hypersensitivity
Genes
Blood Cells
Blood
Chemical activation
Signal transduction
Cushing Syndrome
Gene Regulatory Networks
Glucocorticoid Receptors
Bioinformatics
Computational Biology
Polymorphism
Viruses
Adrenocorticotropic Hormone
Hydrocortisone
Signal Transduction
Sheep
Bacteria
Transcription Factors

Keywords

  • Glucocorticoid hypersensitivity
  • Glucocorticoid receptor
  • Glucocorticoid signalling
  • Glucocorticoids
  • Transcriptomics

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry
  • Clinical Biochemistry

Cite this

Nicolaides, N. C., Lamprokostopoulou, A., Polyzos, A., Kino, T., Katsantoni, E., Triantafyllou, P., ... Charmandari, E. (2015). Transient generalized glucocorticoid hypersensitivity. European Journal of Clinical Investigation, 45(12), 1306-1315. https://doi.org/10.1111/eci.12554

Transient generalized glucocorticoid hypersensitivity. / Nicolaides, Nicolas C.; Lamprokostopoulou, Agaristi; Polyzos, Alexandros; Kino, Tomoshige; Katsantoni, Eleni; Triantafyllou, Panagiota; Christophoridis, Athanasios; Katzos, George; Dracopoulou, Maria; Sertedaki, Amalia; Chrousos, George P.; Charmandari, Evangelia.

In: European Journal of Clinical Investigation, Vol. 45, No. 12, 01.12.2015, p. 1306-1315.

Research output: Contribution to journalArticle

Nicolaides, NC, Lamprokostopoulou, A, Polyzos, A, Kino, T, Katsantoni, E, Triantafyllou, P, Christophoridis, A, Katzos, G, Dracopoulou, M, Sertedaki, A, Chrousos, GP & Charmandari, E 2015, 'Transient generalized glucocorticoid hypersensitivity', European Journal of Clinical Investigation, vol. 45, no. 12, pp. 1306-1315. https://doi.org/10.1111/eci.12554
Nicolaides NC, Lamprokostopoulou A, Polyzos A, Kino T, Katsantoni E, Triantafyllou P et al. Transient generalized glucocorticoid hypersensitivity. European Journal of Clinical Investigation. 2015 Dec 1;45(12):1306-1315. https://doi.org/10.1111/eci.12554
Nicolaides, Nicolas C. ; Lamprokostopoulou, Agaristi ; Polyzos, Alexandros ; Kino, Tomoshige ; Katsantoni, Eleni ; Triantafyllou, Panagiota ; Christophoridis, Athanasios ; Katzos, George ; Dracopoulou, Maria ; Sertedaki, Amalia ; Chrousos, George P. ; Charmandari, Evangelia. / Transient generalized glucocorticoid hypersensitivity. In: European Journal of Clinical Investigation. 2015 ; Vol. 45, No. 12. pp. 1306-1315.
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