Evaluation of FKBP5 as a cortisol activity biomarker in patients with ACTH-dependent Cushing syndrome

J Clin Transl Endocrinol. 2021 Jun 6;24:100256. doi: 10.1016/j.jcte.2021.100256. eCollection 2021 Mar.

Abstract

Purpose: To evaluate the performance of FKBP5 as a cortisol activity biomarker in patients with ACTH-dependent Cushing syndrome (CS).

Methods: This was a prospective, multicenter, nonrandomized, noninterventional study of a cortisol activity biomarker in adult patients (≥18 years) with documented ACTH-dependent, endogenous CS. The impact of surgery on FKBP5 mRNA expression levels in these patients and the difference in expression levels between these patients and healthy controls were evaluated. Cortisol and biomarker samples were collected before and immediately after surgery. A custom NanoString assay was used to quantify FKBP5 mRNA expression levels. The same method was used to analyze healthy volunteer samples collected from a different study.

Results: Surgery was considered successful in 14/24 patients (58.3%) and changes from baseline in serum cortisol were -92.6% (P = 0.0005) and -43.8% (not significant) in patients with successful and unsuccessful surgeries, respectively. A strong positive correlation between FKBP5 and cortisol levels was observed (before surgery: r = 0.72, P = 0.0002; after surgery: r = 0.85, P < 0.0001). After successful surgery, FKBP5 expression levels were similar to those of healthy subjects. In patients without surgical success, FKBP5 levels remained unchanged from baseline and distinct from healthy subjects (P = 0.0025).

Conclusions: Our findings confirm that FKBP5 levels are higher in the presence of excess cortisol exposure in patients with CS and decrease to normal baseline levels after successful surgery. These findings suggest that FKBP5 can serve as a measure of biological cortisol activity and set the stage for the development of an FKBP5 mRNA expression assay as a biomarker of cortisol activity.

Keywords: Biomarker; Cortisol activity; Cushing syndrome; FKBP5.