OR07-07 Once Daily Low Dose Prednisolone/Prednisone Improves Cardiometabolic Profiles in Adrenal Insufficiency: A Double Blind Randomised Crossover Trial

Abstract Disclosure: S. Choudhury: None. K. Lazarus: None. A. Sharma: None. K. Narula: None. C. Go: None. S. Cro: None. T. Thaventhiran: None. B. Khoo: None. T. Tan: None. K. Meeran: None. Background: Prednisolone is the active and biochemically equivalent form of prednisone after conversion by the liver in first pass metabolism. It is a separate drug to methyl-prednisolone. Once daily low dose prednisolone is an alternative treatment to standard thrice daily hydrocortisone, for the treatment of adrenal insufficiency. We present findings from the first ever clinical trial comparing once daily low dose prednisolone with thrice daily hydrocortisone. Methods: This double-blind randomised crossover study treated patients with adrenal insufficiency using either 4 months of low dose prednisolone (2-4 mg) with matching placebo at noon and in the afternoon, or 4 months of standard regimen hydrocortisone (10 / 5 / 2.5 mg) in the first study period, followed by the alternative medication in the second study period. Anthropometrics, biochemical data for cardiometabolic and bone health, and subjective health survey data were collected at Day 1, 30 and 120 of each study period. Results: There was a significant reduction in body weight at 4 months, with a treatment difference of -1.87 Kg (p=0.002) favouring prednisolone treatment. Concordant treatment differences in waist circumference and HbA1c of -2.26 cm (p=0.010) and -1.23 mmol/mol (p=0.001) were also detected. Short term and medium-term bone formation markers were suppressed on prednisolone with a treatment difference of -1.22 µg/L (p=0.035) in osteocalcin levels and -13.8 ng/L (p<0.001) in Procollagen 1 N-Terminal Propeptide. Urinary N-telopeptide levels, a bone resorption marker was also suppressed by -9.34 nmol/mmol (p=0.002) associated with prednisolone. Other cardiovascular markers such as blood pressure, high-sensitivity troponin and CRP, did not show significant differences between prednisolone and hydrocortisone. Subjective health outcomes were measured by the SF-36 survey and Addisons Quality of Life (Addi-QoL) questionnaire. There was no significant difference in any of the SF-36 domains including physical functioning, emotional wellbeing or general health. Addi-QoL scores were comparable between both treatments. Discussion: Once daily low dose prednisolone or prednisone is a safe alternative to thrice daily hydrocortisone to treat adrenal insufficiency, without compromising wellbeing. There is evidence of improved cardiometabolic and glycaemic outcomes with prednisolone. This may be because hydrocortisone is associated with uncoupling from the normal physiological profile of cortisol, or multiple daily doses causing increased steroid exposure. Conclusion: This study supports the routine use of low dose prednisolone, which would further permit longer term studies using real world mortality and morbidity outcomes. Presentation: Saturday, July 12, 2025