Optimising prednisolone or prednisone replacement in adrenal insufficiency

Abstract

Context: Patients with adrenal insufficiency (AI) have higher mortality than the general population, possibly because of excess glucocorticoid exposure at inappropriate times. The cortisol circadian rhythm is difficult to mimic with twice or thrice-daily hydrocortisone. Prednisolone is a once-daily alternative which may improve patient compliance and convenience. Objectives: Prednisolone day curves can be used to accurately down-titrate patients to the minimum effective dose. We aimed to review prednisolone day curves and determine therapeutic ranges at different timepoints after administration. Methods: Between August 2013 and May 2021, 108 prednisolone day curves from 76 individuals receiving prednisolone replacement were analysed. Prednisolone concentrations were determined by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Spearman’s correlation coefficient was used to determine the relationship between 2-, 4- and 6-hour prednisolone levels compared to the validated standard 8-hour prednisolone level (15-25 μg/L). Results: The median dose was 4mg prednisolone once daily. There was strong correlation between the 4-hour and 8-hour (R=0.8829, p ≤0.0001), and 6-hour and 8-hour prednisolone levels (R=0.9530, p ≤ 0.0001). Target ranges for prednisolone were 37-62 μg/L at 4-hours, 24-39 μg/L at 6-hours and 15-25 μg/L at 8-hours. Prednisolone doses were successfully reduced in 21 individuals and of these, three were reduced to 2mg once daily. All patients were well upon follow-up. Conclusion: This is the largest evaluation of oral prednisolone pharmacokinetics in humans. Low dose prednisolone of 2-4mg is safe and effective in most patients with AI. Doses can be titrated with either 4-hour, 6-hour, or 8-hour single timepoint drug levels.

Redefining ITT cortisol thresholds on Abbott platforms to prevent misdiagnosis of adrenal insufficiency

“…In those who have a partial response to the ITT, tapering of glucocorticoid therapy may enable recovery of endogenous cortisol production. 23 Our results are in keeping with studies evaluating stimulated cortisol responses to synthetic adrenocorticotropin (ACTH) using more specific cortisol assays with resultant lowering of cut-off values. 24,25…”

Pituitary–Adrenal Axis and Peripheral Immune Cell Profile in Long COVID

“…Nonetheless, these patients normalised their cortisol values after performing the ACTH stimulation test. For those patients suffering from subclinical adrenal insufficiency, the administration of small doses prednisone or 5-alpha-fluorocortisone may assist in their improvement [ 41 ]. Other researchers have examined the correlation between the adrenal gland, cortisol production, and Long COVID [ 25 , 26 ].…”