期刊
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
卷 45, 期 12, 页码 1306-1315出版社
WILEY
DOI: 10.1111/eci.12554
关键词
Glucocorticoid hypersensitivity; glucocorticoid receptor; glucocorticoid signalling; glucocorticoids; transcriptomics
资金
- European Union (European Social Fund - ESF)
- Greek national funds through the Operational Program Education and Lifelong Learning of the National Strategic Reference Framework (NSRF) - Research Funding Program: THALIS -University of Athens (UOA), Athens, Greece
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 mu g/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 hGR alpha 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-kappa B 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.
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