Endocrine Abstracts

Background: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder characterized by impaired cortisol secretion and androgen excess. The mainstay of CAH treatment is glucocorticoid (GC) replacement, necessary to avoid adrenal crisis and manage androgen excess. The delicate balance between GC under/overtreatment is crucial to prevent metabolic and cardiovascular complications. Dual-release hydrocortisone (Plenadren®) is once-daily modified-release formulation of hydrocortisone (HC) approved for adrenal insufficiency. Data on its use in CAH are scarce. The aim of this study is to evaluate clinical, metabolic and hormonal characteristics of patients with CAH switched from conventional GC treatment to Plenadren.

Patients and method: Retrospective study on 29 patients followed at our Unit (M/F:17/12) with CAH; 18/29 patients were switched to Plenadren (median age 33 years, IQR 24-40). Clinical, metabolic and hormonal data were evaluated at baseline and during follow-up (at 6 months and last available visit) and compared with patients (11/29) who continued conventional GCs.

Results: There were no statistical differences between the two cohorts of patients at baseline. During follow-up, patients switched to Plenadren showed a worsening of ACTH control [123(23-307) vs 193(142-713) ng/l, P=0.09] despite an overall increase of daily HC equivalent dose (13 vs 20 mg/day); other parameters of disease control such as 17-OH progesterone [200 (19-433) vs 254 (99-426) nmol/l, P=0.58] and total testosterone levels in male [12.8 (9.0-19.1) vs 13 (10.0-16.6) nmol/l P=0.99] remained stable, as well as metabolic parameters like HOMA index [2.5 (1.25-2.9) vs 0.8 (0.7-2.5), P=0.20] and total cholesterol [178 (142-206) vs 147 (122-157) mg/dl, P=0.11]. However, comparing with patients on conventional GCs regimen, total cholesterol levels improved [147 (122-157) vs 200 (169-208) mg/dl, P=0,03], but disease control was poorer [ACTH 193 (142-713) vs 50 (19-105) ng/l, P=0.015 and 17-OH progesterone 254 (99-426) vs 24 (7-123) nmol/l, P=0.004]. Unsatisfactory disease control was the main reason for discontinuation (12/18 patients), after a median time of 29 months (6-49), but no adrenal crisis was recorded during follow-up.

Conclusions: Although dual-release HC can mimic the circadian rhythm of cortisol secretion, it provides suboptimal hormone control in CAH. The once-daily administration in the morning has a fall of cortisol level at bedtime, not avoiding the overnight ACTH-driven androgen excess. However, Plenadren is a safe treatment and tends to improve the metabolic profile compared to conventional GCs; thus it could be a reasonable choice in older CAH patients or post-menopausal women, in whom reducing cardiovascular risk factor and adrenal insufficiency are the main aims over obtaining a strict control of adrenal androgens.