Endocrine Abstracts

Background and aim: The dual-release hydrocortisone Plenadren® has shown promising results of improved cardiovascular and metabolic profiles after treatment of adrenal insufficiency, possibly due to an improved circadian profile of cortisol, but results are ambiguous.

Aim: To further investigate the potential effect of dual-release hydrocortisone on the metabolic profile as compared to conventional hydrocortisone in patients with secondary adrenal insufficiency.

Material and methods: Design

An investigator-initiated 21 week open-label switch trial studying the effect of dual-release hydrocortisone vs conventional hydrocortisone on fatigue measured by ecological momentary assessments. In the present study, the metabolic outcome assessments at baseline on conventional stable hydrocortisone therapy and 16 weeks after switch to dual-release hydrocortisone were analysed.

Participants: Patients with adrenal insufficiency due to hypopituitarism and without diabetes (N = 27, 24 men/3 postmenopausal women). Outcomes: 24-h ambulatory blood pressure, body mass index (BMI), body composition assessed by Dual-Energy X-ray absorptiometry scan, blood samples for lipids, fasting glucose, and glycated haemoglobin, and markers of bone turnover (type 1 procollagen, collagen type 1 cross-linked C-telopeptide, osteocalcin, receptor activator kappa-B ligand, osteoprotegerin, and sclerostin).

Results: Median age[range] was 62 years[38–73]. The dose of conventional hydrocortisone and dual-release hydrocortisone did not differ significantly (median[range]: 20[10–35] mg and 25[10–35] mg, respectively, P= 0.1). Ten patients above the age of 50 years had osteopenia at baseline while none were diagnosed with osteoporosis. After 16 weeks of treatment with dual-release hydrocortisone, no change in mean BMI was observed (difference(sem): -0.2(0.2) kg/m², P = 0.2), whereas mean total fat mass was reduced (difference(sem): -1.4(0.4) kg, P = 0.003). Mean total lean mass increased, however, non-significantly (difference(sem): +0.6(0.5) kg, P = 0.3). Mean glycated haemoglobin was reduced (difference(sem): -1.1(0.4) mmol/mol, P = 0.02), but the mean of fasting glucose and lipids did not change. Mean osteocalcin significantly decreased (difference(sem): -7.0(3.1) µg/l, P = 0.03), but the levels of the remaining bone markers were unchanged. No difference was observed in 24-h ambulatory blood pressure.

Conclusions: We observed an improved metabolic profile with reduced total fat mass and glycated haemoglobin as well as a non-significant increase in total lean mass after 16 weeks of treatment with the dual-release hydrocortisone Plenadren® compared to stable conventional hydrocortisone replacement therapy that could be explained by the more physiological circadian profile of dual-release hydrocortisone. However, we also found a decrease in osteocalcin concentrations indicating an inhibition of bone formation which contradicts previous findings.