Endocrine Abstracts

Introduction: Liberal glucocorticoid replacement therapy prevents Addisonian crises in individuals with adrenal insufficiency (AI). Prednisolone is six to eight times more potent than hydrocortisone. There is inter-individual variation in glucocorticoid metabolism wherein 5 mg prednisolone once-daily may result in over-replacement in most individuals, with subsequent long-term morbidity and mortality.

Methods: Data from individuals on established prednisolone replacement therapy at a dose of 5 mg was analysed. All had prednisolone day curves performed between August 2013–May 2021 at Imperial College Healthcare NHS Trust. Pharmacokinetic parameters were assessed. Demographic data and clinical outcomes were obtained using electronic medical records. Data is presented as mean (±SD) and median (IQR) for parametric and non-parametric parameters respectively.

Results: Twenty-six prednisolone day curves were analysed from twenty-six individuals. There were 16 females (62%) and 10 males (38%). Individuals were 54 (±15) years old, with 84.6% diagnosed with secondary adrenal insufficiency. A 5 mg replacement prednisolone dose corresponded to a serum maximal concentration (C_max), of 130.4 (80) μg/l, achieved at T_max 1.7 (±1) hours after administration. The median 8-hour (C_8h) prednisolone level was 31.8 (22.2) μg/l. The half-life of individuals that were ’well’ on 5 mg replacement was 2.7 (1.4) hours vs. 4.3 (1.1) hours in individuals that were ‘unwell’. 80.8% of individuals had C_8h level greater than the established target range of 15-25 μg/l. 92.3% (n=24/26) of individuals felt ‘well’ on a replacement dose of 5 mg. Of these, 33.3% (n=8/24) had successful subsequent reduction of prednisolone dose. 7.7% (n=2/26) reported symptoms of AI despite adequate replacement demonstrated by C_8h >25 μg/l.

Conclusion: Our results demonstrate the inter-individual variability in prednisolone metabolism on a single given dose. For the vast majority of individuals within our cohort, 5 mg was supra-therapeutic. Use of 8-hour prednisolone levels enabled dose reduction, thereby reducing the adverse effects associated with excess glucocorticoid replacement.