Cushing's Syndrome

New biomarker identified for Cushing’s syndrome through whole blood transcriptome analysis

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Whole blood transcriptome can be used to identify biomarkers reflecting the biological impact of glucocorticoids in Cushing’s syndrome, according to a study. Specifically, the gene FKBP5 has been identified as a potential non-hormonal marker for diagnosing Cushing’s syndrome, providing a new tool to supplement current hormone assays.

Researchers analyzed the whole blood transcriptome of 57 patients categorized into groups: overt Cushing’s syndrome, mild Cushing’s syndrome, eucortisolism, and adrenal insufficiency. The samples were divided into a training cohort to establish a Cushing’s transcriptomic signature and a validation cohort to evaluate this signature.

The transcriptomic profile effectively distinguished samples with overt Cushing’s syndrome. Genes predominantly associated with this condition were linked to immune pathways, particularly neutrophil activation. A prediction model comprising 1500 genes, derived from the training cohort, demonstrated significant discriminating value in the validation cohort with an accuracy of 0.82. This model remained robust in a multivariate analysis including neutrophil proportion (P = 0.002). The expression of FKBP5, a gene overexpressed in Cushing’s syndrome and involved in glucocorticoid receptor signaling, could predict the condition with an accuracy of 0.76.

Birtolo MF, Armignacco R, Benanteur N, et al. Whole blood transcriptomic signature of Cushing’s syndrome. Eur J Endocrinol. 2024;lvae083. doi: 10.1093/ejendo/lvae083. Epub ahead of print. PMID: 38970559.