The use of prednisolone versus dual-release hydrocortisone in the treatment of hypoadrenalism

Abstract

The introduction of adrenocortical extract in 1930, improved life expectancy to between two and five years with further increases seen with the introduction of cortisone acetate from 1948. Most patients are now treated with synthetic hydrocortisone, and incremental advances have been made with optimisation of daily dosing and the introduction of multi-dose regimens. Today there remains a significant mortality gap between individuals with treated hypoadrenalism and the general population. It is unclear whether this gap is a result of glucocorticoid over-replacement, under-replacement or loss of the circadian and ultradian rhythm of cortisol secretion, with detrimental risk of excess glucocorticoid at later times in the day. The way forwards involves replacement of the diurnal cortisol rhythm with better glucocorticoid replacement regimens. The steroid profile produced by both prednisolone and dual-release hydrocortisone (Plenadren), provide a smoother glucocorticoid profile than standard oral multidose regimens of hydrocortisone and cortisone acetate. The individualisation of prednisolone doses and lower bioavailability of Plenadren offer reductions in total steroid exposure. Although there is emerging evidence of both treatments offering better cardiometabolic outcomes than standard glucocorticoid replacement regimens, there is a paucity of evidence involving very low dose prednisolone (2-4 mg daily) compared to the larger doses (~7.5 mg) historically used. Data from upcoming clinical studies on prednisolone will therefore be of key importance in informing future practice.

Corticosteroid Replacement Therapy

“…Evidence from 2 randomized-controlled trials (RCTs) has shown a reduction in CV disease risk parameters with modified release hydrocortisone compared to conventional therapy [9]. Though Plenadren® carries a significantly higher cost basis to the other traditional therapeutic glucocorticoid medications and carries a higher vulnerability to malabsorption during intercurrent gastrointestinal illness [16].…”

Circadian Liver Metabolism Affects Management of Type 2 Diabetes Mellitus During Cytokine Storm Due to COVID-19

“…The mRNA level further found to be positively correlated with insulin amount, and PER3 and CRY2 expression negatively correlat-ed with the glycated haemoglobin in blood. Noticeably, BMAL1, PER3, PPARD, and CRY2 genes expression were found to be altered in women with gestational diabetes as compared to the pregnant normoglycemic women [31].…”

Emerging treatment for congenital adrenal hyperplasia

“…The synthetic corticosteroids, prednisone, and prednisolone have longer half-lives than hydrocortisone. Indeed, prednisolone has the same blood profile as Plenadren [20 ▪ ], but it is readily available as an inexpensive generic. Because they are not the ‘physiologic’ glucocorticoid, prednisone and prednisolone are not favored for treating CAH [1], especially in children.…”