The treatment with [lsquo]dual release[rsquo] hydrocortisone (DR-HC) in congenital adrenal hyperplasia: short-term (6 months) and long-term (12 months) follow-up after the switch from conventional glucocorticoids to DR-HC

Abstract

In patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, life-long glucocorticoid (GC) treatment is often required to replace cortisol deficiency and to avoid the ACTH dependent increase of androgen levels. However, in these patients, the multiple daily doses required with conventional GCs can cause cortisol overexposure, leading to an increased risk of metabolic syndrome (MS), an impaired quality of life (QoL) and a poor treatment compliance (TC). The current study aimed at investigating the impact of the switch from twice or thrice daily conventional GCs to once daily dual release hydrocortisone formulation (DR-HC) on metabolic and hormonal profile, QoL, depression status (DS) and TC in a cohort of patients with CAH. Eighteen patients (14F, 4M, 20-29 years) with CAH, chronically treated with hydrocortisone (10-40 mg/day) or prednisone (6.25-10 mg/day) and switched to DR-HC (10-40 mg/day) entered the study and were evaluated before and after 6-12 months of DR-HC. Metabolic and hormonal parameters were measured using routine assays and the MS was evaluated according with IDF criteria. QoL, DS and TC were assessed using AddiQoL Questionnaire, Beck Depression Inventory II (BDI-II) and Morisky 8-items medication Adherence Questionnaire, respectively. At 6-month-follow-up fasting plasma glucose (p=0.01) was significantly reduced, whereas at 12 month-follow-up HDL (p=0.006) and LDL-cholesterol levels (p=0.039) were significantly improved as compared with baseline. A clear diagnosis of MS was performed in one patient at the baseline, but this was not confirmed after 6 and 12 months. No significant change in morning plasma ACTH, UFC, and serum aldosterone, 17-OH progesterone, testosterone, DHEA-S and androstenedione levels were observed and no clinical worsening of symptoms and signs related to hyperandrogenism were reported. Excluding from the analysis the two patients treated with prednisone at baseline, a significant increase in morning serum cortisol levels was registered after 6 months (p=0.039) but it was not confirmed after 12 months. Despite the unchanged fludrocortisone doses, both in the entire cohort (p=0.004) and in the subgroup of patients with salt wasting form (p=0.02) a significant decrease in renin levels was reported at 6-month-follow-up, but it was not confirmed at 12-month-follow-up. Additionally, DS improved both after 6 (p=0.045) and 12 months (p=0.079) whereas TC significantly, progressively, improved after 6 (p=0.013) and after 12 months (p=0.001). In conclusion, the switch from conventional GCs to DR-HC significantly improves MS, DS and TC, maintaining an optimal hormone control in patients with CAH due to 21-hydroxylase deficiency.