Cardiometabolic and psychological effects of dual-release hydrocortisone: a cross-over study

Abstract

Background: Adrenal insufficiency (AI) is associated with increased cardiovascular morbidity and mortality and reduced quality of life (QoL).Optimum glucocorticoid (GC) dosing and timing are crucial in the treatment of AI, yet the natural circadian secretion of cortisol is difficult to mimic. The once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may address unmet needs. Methods:An investigator-initiated, prospective, cross-over study in patients with AI. Following baseline assessment of cardiometabolic risk factors and QoL, patients switched from their usual hydrocortisone regimen to a once-daily dose equivalent of DR-HC and were reassessed after 12 weeks of treatment. Results: Fifty-one patients (21 PAI/30 SAI) completed the study. Mean age was 41.6 years (SD 13), and 58% (n=30) were male. The median daily HC dose before study entry was 20mg (IQR 15-20mg). After 3 months on DR-HC, the mean SBP decreased by 5.7mmHg, p=0.0019 and DBP decreased by 4.5mmHg, p=0.0011. There was also a significant reduction in mean body weight (-1.23kg, p=0.006) and BMI (-0.3 kg/m2,p=0.003). In a sub-analysis, there was a greater reduction in SBP observed in patients with SAI when compared to PAI post DR-HC. Patients reported significant improvements in QoL using three validated QoL questionnaires, with a greater improvement in PAI. Conclusion: Dual-release hydrocortisone decreases BP, weight and BMI compared with conventional HC treatment, even at physiological GC replacement doses. Additionally, DR-HC confers significant improvements in QoL compared to immediate-release HC, particularly in patients with PAI, which is also reflected in the patient preference for DR-HC.

Benefits of dual-release hydrocortisone treatment on central adiposity and health-related quality of life in secondary adrenal insufficiency

“…However, data concerning the role of DR-HC in SAI are scanty, with most studies including retrospective data [11,12] or few patients [9,[13][14][15]. These studies generally report a reduction in BMI and, in some cases, in waist circumference, but they are less consistent on glucose, lipid metabolism and HRQoL improvement [9,[11][12][13][14][15][16].…”

“…To date, studies on the use of HC-DR in SAI were few (including retrospective data) [11,12] or small [9,[13][14][15]. These studies generally reported a reduction in BMI and, in some cases, in waist circumference, but they are less concordant with an improvement in glucose and lipid metabolism as well as with HRQoL [9,[11][12][13][14][15][16]. Furthermore, data were biased by the fact that in some studies, the switch from conventional GC therapy to DR-HC involved the transition from clearly supra-physiological to physiological doses [9,11,14,15], and therefore the improvements observed might have been related to the reduction of the dose rather than to the drug formulation.…”

Nebennieren-Erkrankungen: Morbus Addison

“…Bei einmaliger morgendlicher Einnahme von Plenadren kommt es entsprechend zu einer Annäherung an das physiologische Cortisol-Tagesprofil. Bisherige Daten deuten auf günstige Effekte auf das Gewicht, das Lipidprofil, den Blutdruck sowie das Immunsystem nebenniereninsuffizienter Patienten hin 12 13 14 15 16 17 . Eine Umstellung von konventionellem Hydrocortison auf Plenadren ® ist bei Patienten, die mit der Standardtherapie gut zurechtkommen, nicht erforderlich.…”

Management of Patients With Glucocorticoid-Related Diseases and COVID-19

“…A modified-release hydrocortisone is designed to more closely resemble the physiological cortisol profile (29). This modified hydrocortisone seems to have beneficial effects on the cardiometabolic and immune profile of AI patients compared with hydrocortisone (26,29,30). Furthermore, its improved bioavailability over time leads to ã 20% reduction in the total daily cortisol exposure (29).…”