Endocrine Abstracts

Life-long glucocorticoid (GC) treatment is needed in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, to replace GC deficiency and to control androgens excess. Multiple daily immediate-release-hydrocortisone (IR-HC), characterized by GC overexposure, peaks and troughs, is frequently associated with a suboptimal androgen control, due to ACTH overnight increase. Once daily dual-release-HC (DR-HC), approved for adrenal insufficiency and, despite a near-physiological daily cortisol profile, characterized by suppressed evening cortisol levels, appears not able to avoid ACTH overnight increase and consequent morning androgens excess. A novel twice daily modified-release-HC (MR-HC), recently approved for CAH patients >12 years, simulating the overnight increase of cortisol, appears able to control ACTH overnight increase and consequent morning androgens excess. The current study aimed at investigating the impact of the switch from IR-HC/DR-HC to MR-HC on 3-month metabolic and androgen profiles, and quality of life in 15 CAH females. Nine (60%) patients with classic-form [four (44.4%) with salt-wasting and five (55.6%) with simple-virilizing] and six (40%) with non-classic form, aged 30.1±11.1,15-60 yrs, were enrolled. Seven (46.7%) patients treated with thrice daily IR-HC (23.4±8.2 mg/day) and eight (53.3%) treated with DR-HC (14.4±8.2 mg/day) were switched to equivalent doses of twice daily MR-HC (20.7±7.8 mg/day). The primary outcome was the change from baseline to 3 months of MR-HC in the percentage of patients with good disease control, defined as morning 17OH-progesterone (17OHP)<3 times the upper limit of normal (ULN) and androstenedione within the reference range, according to the phase3 study. Secondary outcomes included changes in hormones and metabolic parameters. Lastly, a questionnaire focusing on asthenia, sleep quality, hyperandrogenisms signs, stress doses and adrenal crises, was administered to all patients before and after the switch. The percentage of patients with controlled disease was 20% (3/15) at baseline and 73.3% (11/15) 3 months after the switch to MR-HC (P=0.0034). Particularly, a significant decrease in testosterone (0.4±0.6 vs 1.3±2.5ULN at baseline, P=0.011) and 17OHP (2.5±3.1 vs 22±21.6ULN at baseline, P=0.005) was observed. No changes were observed in the other evaluated parameters. Considering patients with alterations at baseline, MR-HC resulted in patient-reported benefits including menses restoration (4/4=100%), asthenia (7/9=77.8%), sleep quality (4/8=50%) and hirsutism (1/11=9.1%). In the 3 months before the switch, twelve patients [12/15 (80%)] adjusted their GC doses for fever/surgery/stress events compared with one [1/15 (6.7%)] patient in the 3 months after the switch. No adrenal crises were observed both 3 months before and after the switch. In conclusion, these preliminary data showed that MR-HC improved disease control in CAH females, with overall patient-reported benefits, mainly in menses, asthenia and sleep quality.