FKBP5 Methylation in Adrenal Insufficiency: New Insights Into Assessing the Quality of Glucocorticoid Replacement
Authors' conclusion
The correlation between FKBP5 methylation status, GC replacement dose, and clinical evaluation of therapy suggests a dose-dependent effect of GC replacement on FKBP5 methylation. This encourages further research into the added value of FKBP5 methylation analysis in assessing the quality of replacement therapy. The lower methylation levels in AI compared to CPA suggest a potential impact of the cortisol peaks arising under conventional GC treatment on FKBP5-methylation.
Study context
- Population
- Patients with chronic primary or secondary adrenal insufficiency (AI) on hydrocortisone replacement; comparison with patients with CPA120 AI, 64 CPA
- Participants
- 72 / 48 / 64
- Exposure
- FKBP5 methylation vs glucocorticoid (GC) replacement measures in AI; AI vs cortisol-producing adrenal adenomas (CPA)
- Primary AIn = 72
- Secondary AIn = 48
- CPAn = 64reference
- Outcome
- Correlation of FKBP5 methylation (54 CpG sites, bisulfite pyrosequencing) with GC replacement
Methodological detailsexplorative
- Explorative
Main finding
As reported in the abstract
Correlation of FKBP5 methylation with GC exposure measures
- Significant negative correlations between methylation levels and GC dose, clinical GC replacement score, and salivary and urinary cortisol
Observational data: associations, not effects.
Further findings
Methylation by physician-guided therapy adjustment
- Patients advised to increase GC dose had higher methylation than those advised to reduce or maintain dose
Methylation in AI vs CPA
- AI patients had similar or lower methylation levels vs CPA
Original publication
FKBP5 Methylation in Adrenal Insufficiency: New Insights Into Assessing the Quality of Glucocorticoid Replacement. J Clin Endocrinol Metab. Published 3 July 2025. doi:10. 1210/ clinem/ dgaf383
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