Endocrine Abstracts

Introduction: Glucocorticoid replacement in adrenal insufficiency may be achieved by administering thrice- daily hydrocortisone or once-daily very low dose (2-4 mg) prednisolone. Prednisolone’s longer half-life enables once-daily dosing, improving patient satisfaction and compliance. At very low doses, it has shown no difference in most markers of metabolic risk when compared with hydrocortisone. At Imperial College Healthcare NHS Trust (ICHNT), use of an eight-hour trough prednisolone level enables individual dose titration with a target of 15-25μg/l indicating adequate replacement. However, the optimum timing of prednisolone level sampling and concurrent target ranges remain unexplored. This knowledge is vital in mitigating the adverse effects of under-replacement/over-replacement with prednisolone.

Methods: Data from individuals receiving established prednisolone therapy were retrospectively analysed. All had prednisolone day curves performed between August 2013–May 2021 at ICHNT. Data was derived from prednisolone assay results and electronic medical records. Spearman’s rank correlation coefficient was used to determine the strength and direction of the relationship between 8-hour prednisolone levels vs. 6-hour and 4-hour levels. Target ranges were obtained using Passing-Bablok regression.

Results: 108 prednisolone day curves were analysed from 76 individuals (61% female; mean(±SD) age 61(±13) years; secondary adrenal insufficiency (81.6%)) on a median (range) once-daily prednisolone dose of 4 (2-5) mg. There was strong correlation between 8-hour vs. 6-hour prednisolone levels (r=0.9530, p≤0.0001) and 8-hour vs. 4-hour prednisolone levels (r=0.8829, p≤0.0001). Proposed target ranges: 6-hour prednisolone level of 28-42μg/l and 4-hour prednisolone level of 48-65μg/l. 90% (n=88/98) of individuals with 6-hour levels and 87% (n=85/98) with 4-hour levels within these ranges were ’well’ on their prednisolone dose at time of sampling.

Conclusions: There is a strong correlation between 8-hour vs. 6-hour and 4-hour prednisolone levels. Sampling at earlier time points allows greater flexibility for patients and clinicians, enabling optimisation of prednisolone dose titration.