SAT296 Ambulatory 24-hour Tissue Microdialysis Of Cortisol And Metabolites, A Tool For Precision Management In Addison’s Disease

Abstract Disclosure: I. Botusan: None. K. Berinder: None. P. Methlie: None. T. Upton: None. E. Zavala: None. K. Simunkova: None. D.A. Vassiliadi: None. I. Marinelli: None. G.M. Russell: None. M.A. Grytaas: None. S. Tsagarakis: None. S.L. Lightman: None. E.S. Husebye: None. O. Kampe: None. M. Oksnes: None. S. Bensing: None. Background: The autoimmune attack on the adrenals in AD (Addison’s disease) results in lack of the vital hormones cortisol and aldosterone, rendering AD patients dependent on life-long hormone replacement therapy. Current therapies cannot replicate the physiological well-tuned, circadian and ultradian hormonal oscillations properly, probably contributing to increased mortality, morbidity and reduced quality of life. No established biomarker for treatment monitoring exists hampering treatment optimization. Ambulatory 24-hour dynamic steroid profiling may represent a novel therapy-monitoring tool, providing new insights in different replacement therapy regimes. Aim: We aimed to assess 24-hour profiles of free cortisol and metabolites in patients with AD on different glucocorticoid replacement therapies (GRT) and compare the results with healthy volunteers (HV). Material and methods: The study includes 41 patients with AD on different GRT regimes (hydrocortisone, cortisone acetate, modified release hydrocortisone) and 214 healthy participants. Twenty minute microdialysis fractions were collected ambulatory from abdominal subcutaneous tissue over 24 hours using a novel and portable microdialysis fraction collector (U-RHYTHM). Steroid hormones were analyzed by ultrasensitive liquid chromatography tandem mass spectroscopy (LC-MS/MS). Dynamic biomarkers were used to define hormone parameters in both healthy and hormone-replaced participants, and to assess the “time in range” for patients on GRT compared with the profiles of healthy controls. Results: Free cortisol and cortisone levels were measurable in all AD patients, while 18- hydroxycortisol, and corticosterone were detected only in a few AD patients suggesting the persistence of residual adrenal function. Lower cortisol levels during night were observed in AD compared with controls. Ambulatory 24-hour dynamic steroid profiling revealed marked interindividual variations partially depending on the type of GRT and dosing-regime. Conclusions: The 24-hour profiles of free cortisol and cortisone differs between patients with AD and healthy volunteers. Ambulatory 24-hour microdialysis samplings may provide a novel dynamic tool to monitor GRT in AD providing opportunity for individual dose adjustment. Presentation: Saturday, June 17, 2023