Endocrine Abstracts

Context

E47 is a transcription factor mostly known for its role in B and T cell lineage commitment. Recently E47 was identified as a modulator of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. Patients with Cushing’s syndrome (CS) suffer from an endogenous glucocorticoid excess due to tumour formation associated with a variety of metabolic comorbidities seriously affecting patients’ health status.

Objective

To analyze the role of circulating E47 in blood of patients with endogenous glucocorticoid excess.

Design, setting, and participants

Retrospective cohort study including 120 female patients with CS (ACTH-dependent=79; ACTH-independent = 41) and 26 healthy female controls. Whole blood samples were drawn in the morning after over-night fast.

Outcome measures

E47 mRNA expression levels in whole blood samples of two different CS subgroups, pre- and post-surgery as well as after ACTH stimulation and dexamethasone suppression test in controls and correlation analysis between E47 gene expression and complications of CS.

Results

Mean E47 gene expression levels were significantly lower in patients with overt CS (n = 29) compared to patients in remission (n = 91; P = 0.0391). E47 gene expression in the pre-surgery subgroup of patients (n = 18) with CS was significantly lower than post-surgery (n = 102; P = 0.0215) also in pre /postsurgery data sets of the same patients (P = 0.0166, n = 14). Gene expression also showed significant differences in overt vs. remission (P = 0.016) and pre vs. postsurgery (P = 0.008) subgroups in patients with ACTHindependent (adrenal) CS. Administration of 1 mg dexamethasone overnight did not change E47 mRNA expression. Stimulation with Synacthen resulted in a significant decrease of E47 mRNA expression 30 minutes after i.v. injection compared to baseline measurements. E47 gene expression showed a positive correlation with total serum cholesterol (P = 0.003), low density lipoprotein cholesterol (P = 0.015) measurements and waist-arm-ratio (P = 0.014) in the subgroup of patients with CS in remission.

Conclusions

Generally, the level of E47 mRNA presents with a high level of dispersion both in CS patients and controls. E47 appears to be a GC-dependent gene that is upregulated in situations with endogenous GC excess potentially aiming at reducing metabolic glucocorticoid side effects.