Τίτλος:
Transient generalized glucocorticoid hypersensitivity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Nicolaides, Nicolas C.
Lamprokostopoulou, Agaristi
Polyzos,
Alexandros
Kino, Tomoshige
Katsantoni, Eleni
Triantafyllou,
Panagiota
Christophoridis, Athanasios
Katzos, George and
Dracopoulou, Maria
Sertedaki, Amalia
Chrousos, George P. and
Charmandari, Evangelia
Περιοδικό:
European Journal of Clinical Investigation
Λέξεις-κλειδιά:
Glucocorticoid hypersensitivity; glucocorticoid receptor; glucocorticoid
signalling; glucocorticoids; transcriptomics
